MINISTRY OF HEALTH

GUIDELINES FOR HIV/AIDS

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DIAGNOSIS AND TREATMENT
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(Published with Decision No. 3003/Qð­BYT dated
19/8/2009 of the Minister of Health)

Ha Noi – 2009
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 TABLE OF CONTENTS
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I. DIAGNOSIS AND STAGING OF HIV INFECTION IN ADULTS ...............................7

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1. Diagnosis of HIV infection: .................................................................................7

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2. Staging of HIV infection ......................................................................................7

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II. CLINICAL MANAGEMENT OF PERSONS WITH HIV/AIDS .................................10

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1. Initial assessment:............................................................................................10
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2. Follow­up visits:................................................................................................13
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III. PROPHYLAXIS FOR OPPORTUNISTIC INFECTIONS.......................................14

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1. Co­trimoxazole prophylaxis ..............................................................................14

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IV. APPROACH TO COMMON CLINICAL SYNDROMES IN PATIENTS WITH

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HIV/AIDS ..................................................................................................................19
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1. Prolonged fever ................................................................................................19

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2. Respiratory manifestations ...............................................................................21

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3. Neurological abnormalities (a, b) ......................................................................23

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4. Odynophagia....................................................................................................25
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6. Lymphadenopathy (a) ......................................................................................29

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7. Anemia (a, b)....................................................................................................31

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8. Mucocutaneous manifestations ........................................................................33

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9. Wasting (a, b)...................................................................................................35

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V. DIAGNOSIS AND TREATMENT OF COMMON OPPORTUNISTIC INFECTIONS

.................................................................................................................................38
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1. Fungal diseases ...............................................................................................38

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2. Protozoal diseases ...........................................................................................41

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3. Bacterial diseases ............................................................................................42

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4. Viral diseases...................................................................................................45
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5. Diagnosis and treatment of TB in patients with HIV/AIDS................................47

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VI. ANTIRETROVIRAL THERAPY (ART) .................................................................54

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 1. Goals and Principles of Antiretroviral Therapy..................................................54
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2. Criteria for initiating Antiretroviral Therapy........................................................54

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3. Preparation for readiness to commence Antiretroviral Therapy ........................55

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4. First­line Antiretroviral Regimens:.....................................................................57

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5. Side effects of ARVs drugs and its management:.............................................60

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6. Monitoring of Antiretroviral Therapy..................................................................65

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7. Immune Reconstitution Inflammatory Syndrome (IRIS) ....................................68

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8. First­line treatment failure and second­line regimens .......................................69

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9. Antiretroviral therapy for patients with specific conditions: ................................74

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VII. ANTIRETROVIRAL THERAPY IN PREGNANT WOMEN AND PREVENTION OF

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MOTHER­TO­CHILD TRANSMISSION OF HIV (PMTCT) ........................................81
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1. ARV therapy for HIV­infected pregnant women ................................................81

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2. Antiretroviral prophylaxis for preventing mother­to­child transmission of HIV....83

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3. Other interventions and referral for the mothers and their infants to care and
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treatment services after birth ................................................................................85
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VIII. POST­EXPOSURE PROPHYLAXIS..................................................................86

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1. Post­occupational exposure prophylaxis ..........................................................86

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2. Non­Occupational Post­Exposure Prophylaxis: ................................................89

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PART B ­ DIAGNOSIS, TREATMENT AND CARE FOR CHILDREN LIVING WITH

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HIV/AIDS ..................................................................................................................92
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I. DIAGNOSIS, CLINICAL AND IMMUNOLOGICAL STAGING OF HIV INFECTION IN

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CHILDREN ...............................................................................................................92
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1. Diagnosis of HIV infection in children ...............................................................92

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2. HIV infection staging ........................................................................................93

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3. Diagnosis criteria of advanced HIV infection (including AIDS) ..........................98

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II. CLINICAL MANAGEMENT OF HIV EXPOSED INFANTS AND CHILDREN WITH

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CONFIRMED HIV INFECTION .................................................................................98
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1. Initial assessment:............................................................................................98
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 2. Follow­up visit: ...............................................................................................101
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III. PROPHYLAXIS FOR OPPORTUNISTIC INFECTIONS, IMMUNIZATION

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SCHEDULE ............................................................................................................101
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1. Prophylaxis with co­trimoxazole (CTX) ...........................................................101

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2. Immunization..................................................................................................104
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IV. APPROACH TO COMMON CLINICAL SYNDROMES IN CHILDREN WITH

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HIV/AIDS ................................................................................................................106
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1. Prolonged fever ..............................................................................................106

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2. Respiratory findings........................................................................................108
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3. Neurologic findings.........................................................................................110
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4. Persistent diarrhea (a) ....................................................................................113

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5. Wasting and Failure to Thrive.........................................................................115

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V. DIAGNOSIS AND TREATMENT OF COMMON OPPORTUNISTIC INFECTIONS

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IN HIV INFECTED CHILDREN ...............................................................................116
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VI. ANTIRETROVIRAL THERAPY..........................................................................126

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1. Goals and principles of ART ...........................................................................126

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2. Criteria for initiating ART ................................................................................126

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3. Preparation for readiness to commence Antiretroviral Therapy ......................127

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4. First­line Antiretroviral Regimens:...................................................................129

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5. ARV drug side effects and its management....................................................131

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6. Monitoring Antiretroviral Therapy....................................................................136

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7. Immune Reconstitution Inflammatory Syndrome (IRIS) ..................................138

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8. First­line treatment failure and second­line regimens .....................................140

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9. ART for children with TB.................................................................................143

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10. ARV treatment for children with hepatitis coinfection ....................................144

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ANNEX ...................................................................................................................146
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Annex 1 ­ Clinical and definitive diagnosis criteria of HIV/AIDS­related diseases in

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adults and adolescents ...........................................................................................146
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 Annex 2 ­ Clinical and definitive diagnosis criteria of HIV/AIDS­related diseases in
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children...................................................................................................................155
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Annex 3 ­ Summary of ARV drugs ..........................................................................166

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Annex 4 ­ Pediatric ARV dosages – Standardized with Developmental Indexes of

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Vietnamese Children ..............................................................................................168
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Annex 5 ­ Interactions of ARVs ...............................................................................177

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Annex 6 ­ Severity grading of ARV side effects in adults.........................................179
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Annex 7 ­ Severity grading of ARV side effects in children......................................184
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REFERENCES .......................................................................................................192
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 ACRONYMS AND ABBREVIATIONS
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ABC Abacavir HIV Human immunodeficiency virus

AFB Acid Fast Bacilli HPV Human papiloma virus

AIDS Acquired immunodeficiency HSV Herpes simplex virus

syndrome

DNA Desoxyribonucleic acid LIP Lymphoid interstitial pneumonia

ALT (SGPT) Alanin aminotransferase LPV Lopinavir

anti­HBc Anti­Hepatitis B core antigen MTCT Mother to child transmission

anti­ HBe Anti­Hepatitis B envelop

Antigen

anti­ HCV Anti­Hepatitis C antibody MAC Mycobacterium avium complex

RNA Ribonucleic acid NRTI Nucleoside reverse transcriptase

inhibitor

ARV Antiretroviral drug NNRTI Non­nucleosid reverse

transcriptase inhibitor
AST (SGOT) Asparate aminotransferase

BCG Bacillus Calmett­Guerrin NVP Nevirapine

b.i.d two times per day PCR Polymerase chain reaction

CMV Cytomegalovirus PI Protease inhibitor

d4T Stavudine RTV Ritonavir

ddI Didanosine TB Tuberculosis

EFV Efavirenz TCD4 Lymphocyte T CD4 (+)

DOT Directly observed therapy TDF Tenofovir

ELISA Enzyme­linked immunosorbent t.i.d three times per day

Assay TMP­SMX Trimethoprim­sulfamethoxazol

HAART Highly active antiretroviral therapy 3TC Lamivudine

HBeAg Hepatitis B Envelop Antigen

HBsAg Hepatitis B surface antigen

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PART A ­ DIAGNOSIS, TREATMENT AND CARE FOR
ADULTS LIVING WITH HIV/AIDS

I. DIAGNOSIS AND STAGING OF HIV INFECTION IN ADULTS

1. Diagnosis of HIV infection:

HIV infection in adults is diagnosed on the basis of laboratory

detection of anti­HIV antibody. A person is defined as infected with HIV
when his/her serum specimen is reactive in all three anti­HIV antibody
tests, which rely on different antigens or of different operating characteristics (as
regulated by the Ministry of Health).

2. Staging of HIV infection

2.1. Clinical staging:

Adults with HIV infection are classified into 4 clinical stages depending on
the presence of HIV­related conditions (Table 1).

Table 1: Clinical staging of HIV/AIDS in adults

Clinical stage 1: Asymptomatic

­ Asymptomatic
­ Persistent generalized lymphadenophathy

Clinical stage 2: Mild symptoms

­ Moderate unexplained weight loss (less than 10% of body weight)

­ Recurrent respiratory tract infections (sinusitis, tonsillitis, otitis media,
pharyngitis)
­ Zona (Herpes zoster)
­ Angular cheilitis
­ Recurrent oral ulceration
­ Papular pruritic eruption.

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­ Seborrhoeic dermatitis
­ Fungal nail infections

Clinical stage 3: Advanced symptoms

­ Unexplained severe weight loss (more than 10% of body weight)

­ Unexplained chronic diarrhoea for longer than one month.
­ Unexplained persistent fever (intermittent or constant and lasting for
longer than one month).
­ Recurrent oral candidiasis.
­ Oral hairy leukoplakia.
­ Pulmonary tuberculosis.
­ Severe bacterial infections (pneumonia, empyema, pyomyositis, bone­
joint infection, meningitis, septicemia).
­ Acute necrotizing ulcerative stomatitis, gingivitis or periodontitis.
­ Unexplained anaemia (< 80g/L), neutropenia (< 0.5x109/L), and/or
chronic thrombocytopenia (< 50x109/L).

Clinical stage 4: Severesymptoms

­ HIV wasting syndrome (loss of more than 10% of body weight with
prolonged & unexplained fever or diarrhoea of more than one month
duration).
­ Pneumonia caused by Pneumocystis jiroveci (PCP).
­ Chronic herpes simplex virus infection (orolabial, genital or anorectal)
of more than one month duration, or visceral at any site
­ Oesophageal candidiasis (or candidiasis of trachea, bronchi or lungs).
­ Extrapulmonary tuberculosis
­ Kaposi’s sarcoma
­ Diseases due to Cytomegalovirus (CMV) in retina or other organs.
­ Toxoplasmosis in central nervous system.
­ HIV encephalopathy.
­ Extrapulmonary cryptococcosis including meningitis.

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­ Disseminated disease due to Mycobacteria avium complex (MAC).
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­ Progressive multifocal leukoencephalopathy (PML).
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­ Chronic diarrhea due to Cryptosporidia.
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­ Chronic diarrhea due to Isospora
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­ Disseminated mycosis (penicilliosis, extrapulmonary histoplasmosis).
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­ Recurrent septicemia (including non­typhoid salmonellosis).
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­ Cerebral or B cell non­Hodgkin lymphoma.
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­ Invasive cervical carcinoma.
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­ Atypical disseminated leishmaniasis.
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­ HIV­associated nephropathy.
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­ Myocarditis due to HIV.
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2.2. Immunological staging:

Immune status of adults with HIV infection is evaluated by

number of CD4 cellsof the patient.

Table 2: Immunological staging of HIV/AIDS in adults

Severity CD4 cell count/mm3

Normal or not significant deficiency > 500
Mild deficiency 350 ­ 499
Advanced deficiency 200 ­ 349
Severe deficiency < 200

2.3. Criteria for diagnosis of advanced HIV infection (including AIDS):

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­ Any stage 3 or stage 4 clinical condition (presumptive or definitive

diagnosis)
and/or
­ CD4 cell count < 350 cells/mm3
AIDS is defined as clinical diagnosis (presumptive or definitive
diagnosis) of any stage 4 condition or CD4 cell count < 200 cells/mm3

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II. CLINICAL MANAGEMENT OF PERSONS WITH HIV/AIDS

1. Initial assessment:

1.1. Clinical and laboratory assessment:

1.1.1. Taking present and previous medical history:
− History of HIV testing: time of detection, place of testing, risks
behaviour of HIV infection (injecting drug use, unsafe sexual practices),
duration of risks behaviours.
− History of TB and TB treatment (time of diagnosis and treatment, place
of treatment, treatment regimen and outcome); history of exposure to
TB source.
− History of OIs, sexually transmitted and other diseases
− Obstetric, gynecological history, use of contraceptive methods
− History of drug allergy to antibiotics (such as cotrimoxazole) and
antiretrovirals
− Recently developing signs and symptoms, their progress and response
to treatment, especially TB­related symptoms.
− Medications used recently:
o OI prophylaxis (cotrimoxazole)
o ARV treatment: reason for use, duration, specific regimen, drug
source, treatment adherence
o Other medications used
− Status of drug and other substances dependence, including injecting
drug and opioid use, substitution treatment (e.g. methadone
maintenance therapy); history of alcohol use and cigeret smoking…
− History of nutrition
− History of HIV infection in the family: any other family members with HIV
infection; if yes, whether ART is given and where ART is provided;
issues of HIV status disclosure of patients and their family members (if
any)
1.1.2. Physical examination: Do thorough and meticulous physical
examination
− Vital signs, body weight, pain symptoms.

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− Assessment of functional status: able to worknormally, ambulatory, or
bed­ridden
− General condition, mucocutaneous manifestations
− Visual ability, Ear­Nose­Throat status
− Neurological symptoms: meningeal syndrome, focal neurological signs
− Respiratory and circulatory organs
− Abdominal conditions, enlarged liver and spleen, lymph nodes and
abnormal intra­abdominal mass
1.1.3. Laboratory:
− CBC, Hb, ALT
− Chest X­ray, sputum AFB in case of suspected pulmonary TB; other
investigations necessary for diagnosis of extrapulmonary TB and other
OIs
− CD4 (if available).
− Lab tests supporting selection of ARV regimen such as HBsAg, anti­
HCV (if available).
− Creatinin, lipid, glucose in case the patient is using TDF or protease
inhibitors
− Pregnancy tests as needed.
1.1.4. Diagnosis of OIs and clinical staging:
− Diagnosis of progressive tuberculosis: (see Chapter V, Section 5:
Diagnosis and treatment of TB in patients with HIV).
− Diagnosis of other OIs: see Chapter IV (Approach to common clinical
syndromes in people living with HIV/AIDS) and Chapter V (Diagnosis
and Treatment of common opportunistic infections).
− Clinical staging (see Table 1).

1.2. Management:
− Provide treatment for opportunistic infections and other conditions,
symptom releave
− Provide prophylaxis for opportunistic infections
− Assess for eligibility to ARV treatment. If the patient is eligible, , follow
preparation for treatment readiness

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− Hospitalize cases with severe conditions; seek consultation orrefer
patients to at higher level if in the case is to complicated to manage at
the localfacilities ; collaborate with TB services, dermatovenereology
and obstetrics specialists, with program for prevention of mother to child
transmission of HIV and other specialties as needed.

1.3. Counseling and support:

Counseling and support should be provided to all patients with HIV
infection both on ARVs or not receiving the ones. Contents of counseling
session arebased on assessment need of each patient’s needs:
− Psycho­social support and introduction of supportive services
− Provision of knowledge on HIV/AIDS
− Explanation about life­long care and treatment
− Counseling on positive living and nutrition
− Counseling on pregnancy and HIV­related issues
− Counseling on prevention of HIV transmission and safe practice
− Counseling on treatment adherence: importance and contents of
treatment adherence, especially to patients on ARV treatment
− Counseling on the necessity of having a treatment supporter when
patient enrolled in the treatment program
− Counseling on disclosure of HIV status to family members and partners.
− Referral of other family members to services such as voluntary
counseling and testing, as needed

1.4. Follow­up plan and other necessary supports

1.4.1. Schedule for follow­up visits for each patient:

− For patients not receiving ART: Follow­up visits should be scheduled on
the basis of clinical stage and CD4 cell count:
⇒ Clinical Stages 1, 2 and CD4 > 350 /mm3: follow­up visit at
every 3 months and whenever abnormal manifestations occur.
⇒ Clinical Stages 1, 2 and CD4 < 350 /mm3; Clinical Stage 3 and
CD4 > 350 /mm3: follow­up visit at every 1­2 months and
whenever abnormal manifestations occur.

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− For patients eligible to ART: follow­up visit should be scheduled to
prepare for treatment readiness.
− For patients on ART: follow­up visit as scheduled.
1.4.2. Explan to patients to come to health facilities whenever abnormal
manifestations occur in order to be timely managed.
1.4.3. Dispense medications as scheduled by the care and treatment team.

2. Follow­up visits:

Patients should come to HIV care and treatment facilities for follow­up visit as
scheduled or whenever abnormal manifestations occur.

2.1. Clinical examination and laboratory testing:

− Taking history: symptoms newly occurred since the last visit, such as
fever, weight loss, cough, diarrhea, eruption, etc.; psycho­social issues,
treatment adherence.
− Clinical examination: general and specific organsexamination for
detection of opportunistic infections and other conditions, side effects of
prophylactic and therapeutic medications. Re­assess clinical staging.
− Perform routine tests, CD4 cell count; diagnostic tests for OIs and
detection of drug side effects as well as treatment failure, as needed.

2.2. Management:
Management will be provided depending on the clinical condition and test
results of the patient.
− Treatment for OIs and management of drug side effects if any.
− Consideration of ARV treatment if patient is eligible.
− Psycho­social counseling and support for treatment adherence.
− Referral for patients to other relevant services.

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III. PROPHYLAXIS FOR OPPORTUNISTIC INFECTIONS

1. Co­trimoxazole prophylaxis

Objective: CTX is effective to prevent opportunistic infections including

PCP, toxoplasma encephalitis, as well as other bacterial and protozoal
infections that cause pneumonia, diarrhea.

1.1. Indication of Co­trimoxazole prophylaxis

If CD4 is available, start cotrimoxazole prophylaxis for:
− Persons with HIV infection at clinical stages 3 and 4, regardless of CD4
cell count.
− Persons with HIV infection at clinical stage 1 and 2 if CD4 < 200
cells/mm3
If CD4 cell count not available, start cotrimoxazole prophylaxis for:
− HIV­infected patients at clinical stage 2, 3 or 4.
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Pregnant women should start Cotrimoxazole prophylaxis regardless of
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period of pregnancy. Breastfeeding women should continue cotrimoxazole
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prophylaxis.
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1.2. Dosage for prophylaxis

− Co­trimoxazole 960mg (SMX800mg/TMP160mg) orally once per day or
three times per week.
− Alternatives (in case of Co­trimoxazole intolerance): Dapsone
100mg/day. Dapsone is less effective than Co­trimoxazole in preventing
PCP.

Note: Co­trimoxazole and ARVs (especially nevirapine and efavirenz) can

cause rash. Co­trimoxazole prophylaxis should be given 1­2 weeks prior to
ARV treatment tohelp with differentiation of side effects between the drugs
if occur.

1.3. Contraindication: allergy to sulphonamides

1.4. Common side effects of Co­trimoxazole:

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− Vomiting and nausea can be seen, commonly within 1­2 weeks after
starting prophylaxis. Co­trimoxazole rash can be of mild, moderate or
severe grade (see Table 3). Severe side effects due to Co­trimoxazole
such as anemia, granulocytopenia, hepatotoxicity are uncommon.
− Counsel the patients about potential side effects for self monitoring; tell
the patients to come immediately to health facilities when signs of
severe side effects occur.
− Perform complete blood count, liver enzyme measurement when
anemia or hepatotoxicity is suspected.
Table 3: Grading and management of co­trimoxazole rash

Grade Clinical manifestations Management recommendations

Grade 1 • Continue Co­ trimoxazole

Erythema prophylaxis, with close daily
(mild)
monitoring.
Grade 2 Diffuse maculopapular • Symptomatic treatment and
(Moderate) rash, dry desquamation antihistamines.

• DISCONTINUE the drug until

symptoms resolve (usually after 2
weeks).

Grade 3 Vesiculation, mucosal Symptomatic treatment and

(Severe) ulceration antihistamines.

• Then CONSIDER TO
REINTRODUCEco­trimoxazole
with desensitization.

Exfoliative dermatitis, • PERMANENTLY DISCONTINUE

Grade 4 Stevens­Johnson Co­ trimoxazole
(Very syndrome or erythema
multiforme, moist • Symptomatic treatment and
severe)
desquamation antihistamines

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Co­trimoxazole desensitization in adults:

− Co­trimoxazole desensitization can be attempted in patients with

mild and moderate allergy (grades 1 and 2); patients with severe
allergy (grade 3) should be desensitized cautiously. Desensitize
should not be attempted in patients with very severe allergic
reactions to Co­trimoxazole or other sulphonamides in history
− Desensitization should be commenced about 2 weeks after
discontinuing Co­trimoxazole when patients’ symptomes resolved.
Desensitization should preferably be performed in hospital, where
intensive treatment for anaphylactic shock available if needed
− Desensitization is commenced according to the following protocol
(see Table 4); dose of desensitization is increased only if patients do
not develop hypersensitivity to previous dose of cotrimoxazole (no
rash). If a reaction occurs, the desensitization should be stopped.
Once the patient recovers fully, dapsone can be used as
substitution.

Table 4: Desensitization protocol for co­ trimoxazole

Step Dosage

Day 1 80 SMX + 16 mg TMP (2ml of oral suspension(*))

Day 2 160 SMX + 32mg TMP (4ml of oral suspension(*))
Day 3 240 SMX + 48mg TMP (6ml of oral suspension(*))
Day 4 320 SMX + 64mg TMP (8ml of oral suspension(*))
Day 5 One single strength (480mg) tablet
From day 6 Two single strength (480mg) tablets or one double­
strength (960mg) tablet

(*) Oral suspension of Co­trimoxazole contains 200mg SMX + 40mg TMP in each 5ml. In case
oral suspension not available, dissolve 400mg SMX + 80mg TMP tablet and use in dosage as
above.

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1.5. Duration of co­ trimoxazole prophylaxis for adults with HIV
infection:

Table 5: Duration of Co­trimoxazole prophylaxis for adults with HIV

infection

Patient Management

Patients not
Life­long prophylaxis
receiving ART

Patients on Discontinuation of prophylaxis: Co­trimoxazole

ART prophylaxis should be discontinued if the patient has CD4
> 200 cells/mm3 for at least 6 months. If CD4 cell count is
not available, discontinue Co­trimoxazole prophylaxis
when the patient receives ARV treatment for at least 1
year with good adherence and without clinical
manifestations related to HIV.

Reintroduction of prophylaxis: Co­trimoxazole

prophylaxis should be reintroduced when the patient has
decreased CD4 count <200 cells/mm3

2. Prevention of active tuberculosis with isoniazide (INH)

− Objective: prevention of latent TB infection to become active TB
disease
− Criteria for prophylaxis: All HIV infected people (adults and children)
with no active tuberculosis on TB screening.
− Regimen: oral isoniazide (INH) 5 mg/kg/day (maximal dose in adults is
300 mg per day) given daily for 9 months in combination with vitamin
B6, 25 mg daily.
− Monitoring and evaluation: Deliver the drug monthly and evaluate the
drug use at least once a month. Management of stopping therapy: lost:
if the patient missed less than 50% of total doses, give additional doses

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 for treatment to be completed; if missed over 50% of total doses, the
treatment should be restarted.
− Side effects:
• Mild: peripheral neuropathy – manage with vitamin B6
100mg/day.
• Severe: liver involvement (jaundice, anorexia, elevated liver
enzymes).
• Management: stop INH and refer to healthcare facilities for
treatment. Advice patients not to drink alcohol or beer during
treatment.

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 IV. APPROACH TO COMMON CLINICAL SYNDROMES IN PATIENTS WITH
HIV/AIDS

1. Prolonged fever

Prolonged fever (a, b)

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Give antipyretics, counsel on nutrition 

­ History taking (c)

­ Physical examination (d)

Suggestive causes of fever (e):

Routine analyses and symptom­based
­ Respiratory findings: TB, PCP, bacterial
investigations (e):
pneumonia ­ CBC, CD4 (if available)
­ Neurological findings: bacterial, TB, cryptococcal
­ Respiratory findings: CXR, sputum for
meningitis; toxoplasmal encephalitis
AFB
­ Skin lesions: penicilliosis
­ Neurologic findings: CSF analysis
­ Lymphadenopathy: TB, MAC, fungal septicemia
­ Septicemia, penicilliosis: blood culture
­ Diarrhea: salmonellosis, TB enteritis, MAC
­ Lymphadenopathy: lymphnode
­ Anemia: TB, endocarditis, MAC, fungal
aspiration and cytology
septicemia, malaria
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­ Prev. history with using medication: allergy
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Empirical treatment (e):

­ Septicemia: appropriate antimicrobials
­ Penicilliniosis: itraconazole
­ PCP: co­trimoxazole Diagnosis confirmed by analyses and
­ TB: anti­TB drugs, or anti­ MAC treatment if no investigation, and/or
Patient responds to empirical therapy
response
­ Bacterial or cryptococcal meningitis: appropriate
antimicrobials
­ Toxoplasma encephalitis: co­trimoxazole
­ Etc...
­ Continue and complete treatment.
­ Maintenance treatment if indicated
No confirmations for diagnosis, patient does not
respond to empirical treatment

­ Re­evaluate clinically, consider other causes,

especially TB, MAC or HIV related fever
­ Do appropriate analyses and investigations,
consider lymph node and bone marrow biopsy,
CT scan, echocardiography, etc.
­ Treat presumptively for TB, consider MAC if no
response
­ Consider ART

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Instructions:

(a) Definition: prolonged fever is defined as a fever over 38,50C lasting for
more than 14 days without any causes determined.

(b) Common causes of prolonged fever

­ OIs: TB, penicilliosis, cryptococcal meningitis and fungemia,
septicemia due to salmonella and other bacteria, MAC, etc.
­ HIV related neoplasms, such as lymphoma
­ Drug reactions such as hypersensitivity to CTX, NVP, ABC, etc.
­ HIV related fever, malaria
(c) History taking:
­ Symptoms from organs and systems: headache (meningitis due to
cryptococcus or TB, Toxoplasmosis), diarrhea (salmonella
septicemia, MAC, etc.), cough (pulmonary TB), rash (penicilliosis,
drug allergy), etc.
­ Drugs taken: CTX, ARV, others.
­ History of any OI or other HIV associated conditions (potential
recurrence of OIs if secondary prophylaxis or ARV treatment not
given)
­ History of drug allergy and other conditions.
­ History of IDU (septicemia with Staphylococcus aureus), unsafe sex
(gonorrhea, syphilis, other STIs)
­ Family history: TB, cough and other communicable diseases
(d) Clinical examination: Examine all systemsandorgans , focus on the
ones with symptoms.
(e) Refer to causes of OIs, investigations and treatment in Section V
"Diagnosis and treatment of common Opportunistic Infections”.

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2. Respiratory manifestations
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Respiratory symptoms (a, b)

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­ Normal CXR or diffuse infiltration

or pneumothorax Consider PCP, give
­ Mild to moderate dyspnea
­ Take history and assess clinically (c) treatment trial with
­ Gradual onset, severely
immunocompromised CTX (e)
­ Routine laboratory tests
­ Chest X ray, sputum for AFB (d)
Diagnostic steps for
­ Other necessary tests and ­ CXR suggestive of TB
investigations AFB (­) pulmonary
­ Chronic or subacute onset
TB as followed
­ Productive cough, fever, with or
without cachexia National guidelines
(d)
AFB (­)

AFB (+) ­ Acute onset

­ Fever, productive cough, chest pain Consider
Treat for TB (±) pneumococcal
­ CXR: lobar infiltration pneumonia. Treat with
antibiotics (e)

Treat for causes if ­ History of IDU Consider

defined (e) ­ Fever, dyspnea staphylococcal
­ CXR: diffuse nodular pneumonia ±
infiltrations
endocarditis; treat with
antibiotics (e)

No improvement:
­ Re­assess clinically
­ Repeat essential lab investigations (CXR, sputum
AFB, blood culture, lymph node aspiration, etc.)
­ Consider TB treatment if not done before
  21 ­ Consider other causes (fungi, CMV) and proper
treatment
Instructions:
(a) Respiratory symptoms: cough dyspnea; often associated with fever
(b) Causes:
­ Common causes: pleuro­pulmonary TB, PCP, MAC, bacterial pneumonia.
­ Other causes: penicilliniosis, cryptococcosis, histoplasmosis (causing
respiratory symptoms with systemic fungal infection); cytomegalovirus
disease; non­infectious causes: lymphoma, Kaposi’s sarcoma.
(c) Considerations in history taking and physical examination:
History Taking: Physical examination:
­ Onset: acute or chronic ­ Respiratory failure: dyspnea,
­ Dyspnea: effort­related or not cyanosis
­ Characteristics of the sputum ­ General conditions: fever, weight
­ Accompanied symptoms: fever, loss, skin eruption,
chest pain… lymphadenopathy, etc.
­ History of IDU ­ Lungs: crackles, fremitus,…
­ TB history of the patient and in family ­ Findings of immunodeficiency: oral
thrush, cachexia…

(d) Investigations: Based on clinical signs & symptoms and history

­ Routine laboratory tests, CD4 cell count,
­ Chest X­ray, sputum AFB; sputum microscopy and culture to look
for other bacteria.
­ Blood culture in case of fever
­ Pleural tapping and lymph node aspiration in case of pleural
effusion and lymphadenopathy; analysis of pleural fluid and lymph
node aspirate
­ Chest CT scan if available
(e) See the Section V "Diagnosis and treatment of common Opportunistic
infections "

  22
3. Neurological abnormalities (a, b)

­ Take history (c)

­ Do clinical examination (d)
­ Do routine and clinically oriented lab
investigations
Meningeal signs
­ Do brain CT scan if any focal neurological
suspected
signs or in case of persistent illness

Lumbar puncture (g)

CSF analyses for protein, glucose, cytology
Microscopy for bacteria, AFB and fungi, and
bacterial culture
Focal neurological signs present and/or

suspected lesions of encephalitis due to

Toxoplasma in brain CT scan (f) Diagnosis based on clinical assessment
and CSF analysis (h):
­ Cryptococcal meningitis
­ TB meningitis
­ Bacterial meningitis
Give appropriate antibiotic treatment

Continue investigations
No Consider other causes (TB
Treat presumptively for Toxoplasmal Improved after 1 week meningitis, encephalitis,
encephalitis of treatment?
lymphoma, etc.)
Refer to higher levels if not able
to do necessary investigations
Yes

Complete the treatment

  23
Instructions:
�
(a) Neurological signs and symptoms: Headache, altered consciousness, focal
neurological signs
(b) Causes:
­ Opportunistic infections in CNS: Toxoplasma encephalitis, cryptococcal, TB or bacterial
meningitis
­ Other causes: lymphoma, HIV­related encephalopathy, progressive multifocal
leukoencephalopathy (PML)
­ Medications: d4T, EFV
(c) History Taking:
­ Duration of symptoms
­ Accompanied symptoms: fever, skin eruption, wasting, etc.
­ TB history of the patient and in the family
(d) Clinical examination:
­ Look for neurological abnormalities: altered mental status, meningeal signs
(headache, neck rigidity, photophobia), focal neurological signs (hemiplegia, cranial
nerve palsies).
­ Look for constitutional signs: fever, lymphadenopathy, skin eruption, manifestations of
immunodeficiency
(e) Lab tests and investigations: based on history and clinical examination
­ Blood culture if fever presents
­ Chest X ray and other lab tests if TB meningitis is suspected
(f) Typical lesions of toxoplasmal encephalitis: treat as indicated in the Section of
Opportunistic infections. Other lesions: consider TB meningoencephalitis, bacterial abscess,
HIV encephalopathy, etc; perform appropriate assessment and investigations.
(g) Suggestive differential diagnosis based on cerebrospinal fluid (CSF) changes:

Opening Protein
CSF Cell count Microscopy Culture
Pressure content
Cryptococcal Very high Slightly Slightly elevated + +
meningitis elevated or or normal India ink
normal stain
TB meningitis High or Slightly Elevated +/­ ­ ­ +/­
normal elevated to (lymphocytes
very high predominate)
Bacterial High Very high Granulocytes +/­ +
meningitis predominate
Toxoplasmal Normal Normal or Normal ­ ­
encephalitis slightly
elevated
Lymphoma Normal Normal Normal ­ ­

  24
(h) See the Section V "Diagnosis and treatment of common Opportunistic infections”

4. Odynophagia

Odynophagia (a, b)

Treat presumptively
for esophageal
candidiasis (c) 

Consider
� Improved after
presumptive
� Esophago­
Improved within 7 days of
treatment for
� No scopy
7 days of No treatment
treatment herpes simplex
�
(d)
Yes
Yes
No

­ Continue the treatment

­ Continue the treatment
for 14 days
for 14 days
­ Prophylaxis with CTX;
­ Prophylaxis with CTX;
Start ARV treatment  
Start ARV treatment

Instructions
(a) Definition: odynophagia is painful feeling in the throat and retrosternal
space on swallowing food, with or without dysphagia, which usually is a
symptom of esophagitis.
(b) Causes of odynophagia in HIV patients:
­ Candida esophagitis
­ Herpes simplex virus esophasitis
­ Cytomegalovirus esophasitis
­ Aphthous ulcer
­ Kaposi’s sarcoma, lymphoma of esophagus
(c) Treatment for esophageal candidiasis and Herpes simplex ­ see the
Section V "Diagnosis and treatment of common Opportunistic Infections".

  25
 5. Chronic diarrhea (a, b)
�
­ Take history (c)
­ Do clinical examination (d)
Evaluate severity of dehydration; give
rehydration, correct electrolyte
disturbance, counsel on proper diet

Stool microscopy and Causes not found

� Stool examination not
culture for causes, available
other lab tests and
investigations (e) Treatment trial with
fluoroquinolone
Yes and metronidazole
(f) for 7 days
Treat for
detected causes No
Albendazole + CTX (g)
Improved?
Treat with loperamide (h)
Yes ­ Consider other causes,
No such as TB, MAC; give
Complete the Improved? appropriate treat ment
treatment in 14 days
­ Consider ARV treatment
Yes
­ Give CTX prophylaxis
Complete the
treatment for 21
days
  26
Instructions:

(a) Definition: �Chronic diarrhea is defined as loose or watery stool of more

than 3 times per day, lasting for more than 14 days
(b) Causes of diarrhea:
­ Bacterial infections: Salmonella, Shigella, Campylobacter

­ Protozoal and helminthic infections: Giardia, Entamoeba,

cryptosporidium, Isospora, Microspora, Strongyloides

­ Mycobacterial diseases: TB, MAC

­ Viral diseases: CMV

­ HIV­related malignancies: Kaposi’s sarcoma, lymphoma

­ HIV itself

(c) � History Taking:

­ Frequency of bowel movement each day, characteristics of stools

­ Accompanied symptoms: fever, abdominal pain, location and

�
characteristics of pain
�

­ History of ARV treatment and using other drugs; antibiotics used for
diarhea treatment

­ History of TB and other communicable diseases in the family

(d) � Clinical examination:

­ Evaluate general condition, dehydration and nutritional status

­ Look for constitutional symptoms: fever, lymphadenopathy,

�
examination of respiratory and cardiovascular systems
�

­ Examine the abdomen: tenderness, ascites, hepatosplenomegaly,

enlarged intra­abdominal lymph nodes

(e) Lab tests and investigations:

­ Stool microscopy for erythrocytes and white blood cells (invasive
diarrhea); protozoal parasites (entamoeba, giardia), strongyloides
larvae, hookworm and other helminthic eggs; formalin­ether
concentration and modified acid­base staining for Cryptosporidium and
trichrome staining for Microsporidium and isospora; AFB (TB and
MAC) if available

­ Blood culture if febrile and septicemia associated diarrhea suspected

  27
 ­ Chest X ray, sputum examination if having respiratory findings or TB is
�
suspected

­ Abdominal ultrasound if available to confirm hepatosplenomegaly,

abdominal lymphadenopathy and ascites

(f) � Oral Fluoroquinolone (oral ciprofloxacin 500mg or ofloxacin 200mg twice

daily) + metronidazol 500 mg twice daily. Effective against shigella,
salmonella, campylobacter, entamoeba and giardia. TB should be
excluded before treatment with fluoroquinolone
(g) � Albendazol 200 mg 2­ 4 times/day + co­trimoxazole 960 mg 1­2
times/day. Active against isospora, microsporidia, strongyloides
(h) � Loperamide initially 4 mg, then 2 mg after each 4 hours if unformed stool
continues; maximal dose: 16 mg/day. Do not use loperamide in patients
with bloody and mucous diarrhea.

  28
 6. Lymphadenopathy (a)
�

­ Take history (b)

­ Do clinical examination (c)

Following signs and Yes Look for findings suggestive of TB, bacterial, fungal causes. Perform
symptoms present (?): routine tests (d)
­ Fever
­ Weight loss
­ Asymmetric lymph nodes Local lymphadenitis, recent Fever, weight loss, local or
­ Congregated lymph history of IDU generalized
nodes lymphadenopathy, other
­ Soft nodes suggestive symptoms of TB
­ Manifestation in organs Consider treatment for
staphylococcal infection (e),
No Blood culture if available Lymph node aspiration,
microscopy for AFB and TB
Persistent Improved lesions, and culture for fungi
generalized No improved and bacteria
lymphadenopathy (c) Complete the treatment

TB lymphadenitis Causes found

Treat for TB (e)
Yes

Other causes: bacteria, No

Treat for causes found
fungi, MAC, malignant Do biopsy for causes, consider
(e)
tumors treatment for TB, MAC
Refer if investigations not available

Instructions:

(a) Causes: enlarged lymph nodes in symptomatic patients are often caused
by infections or malignancies. Infectious causes: TB, Penicillium,
Cryptococcus, Staphylococcus, maybe MAC; Nocardia, syphilis, histoplasma,
leishmania. Malignant causes: lymphoma, Kaposi’s sarcoma. HIV itself
(persistent generalized lymphadenopathy in asymptomatic HIV infected patients).
(b) History Taking:
­ Duration of lymphadenopathy, accompanied symptoms: fever, pain around
swelling node, skin eruption, cough, etc.

 29
­ History of diagnosis and treatment for OIs (penicilliniosis, TB, etc.) and
other diseases
(c) Physical Examination: Assess general condition, look for constitutional
manifestations, s.a. fever, cachexia, throat thrush, skin eruption, anemia, etc...
­ Examine lymph nodes, evaluate their size and characteristics
­ Look for manifestations in other organs, enlarged abdominal lymph nodes,
hepatosplenomegaly
(d) Routine lab tests: complete blood count, CD4 cell count if available, CXR
(e) See the chapter on Diagnosis and treatment of Opportunistic
Infections

 30
 7. Anemia (a, b)
�

• Take history (c)

• Do clinical examination, CBC (d)

Provide symptomatic treatment, blood transfusion if

needed, vitamin B12, folat, nutrition

On medications Look for OI causes (e) Malnutrition, blood loss

(AZT, CTX…)
No

­ TB, MAC, ­ Odynophagia, diarrhea

­ Endocarditis ­ Blood loss
­ Fungemia ­ Inadequate nutrition due
Yes to inadequate intake
­ Malaria

Substitute AZT with

d4T

Provide appropriate
treatment

Evaluate further, consider

No HIV­related anemia
Improved
Treat with ARV, avoid AZT
Yes

Complete the
treatment

 31
�
Instructions:
(a) Definition: Anemia is defined as having hemoglobin of < 120g/l for males
and < 100 g/l for females.
(b) Causes:
­ Infections: TB, systemic fungal disease, endocarditis, MAC, malaria.
­ Malnutrition, dysphagia, chronic diarrhea
­ Drugs: AZT, CTX, etc.
­ Blood loss, medical conditions causing bone marrow depression
­ Malignancy and due to HIV itself
(c) History Taking:
­ Duration of symptoms associated with anemia, (fatigue, tinnitus, dazzle,
dizziness)
­ Other symptoms, s. a. fever, diarrhea, odynophagia, cough, skin
eruption, etc.
­ History of opportunistic infections
­ History of using co­trimoxazole, AZT and other drugs
­ History of IDU and traveling to malaria areas
­ History of blood loss, nutritional uptake
(d) Clinical examination
­ Evaluate the severity of anemia, nutrition and look for manifestations of
OIs
(e) Laboratory analyses and investigations:
­ CBC: Hb, other cell lines; mean corpuscular volume (MCV) (macrocytic
anemia suggests vitamin B12 deficiency, co­trimoxazole and AZT
associated anemia; microcytic anemia suggests OIs, blood loss).
­ Malaria film.
­ Diagnostic tests for OIs: sputum AFB, tests for fungi
­ Bone marrow analysis, lymph node biopsy, bone marrow biopsy and
other investigations if available

 32
8. Mucocutaneous manifestations
�

Papules Vesicles, ulcers Maculo­papular Other HIV­associated

Eruption Eruptions or conditions

­ Penicillium marneffei ­ Vesicles limited in a ­ Drug reaction, ­ Sally erythema along the
(umbilical papules with central dermatome with burning ­ Syphilis nose­cheek groove, scalp
necrosis) sensation or pain: ­ Scabies: papules, very border: seborrheic
­ Molluscum contagiosum, Herpes zoster (Zona) itchy, burrows may seen, dermatitis.
Cryptococcal infection or TB. ­ Scattered blisters: may present as ­ Eosinophilic folliculitis:
­ Genital condyloma acuminata: consider Herpes simplex Norwegian scabies acne­like lesions on the
wart­like lesions ­   face, chest and back
­ Pruritic eruption: seen in
severe immunodeficiency
­ HIV­related dry and itchy
skin
­ Penicilliniosis suspected: skin ­ Acyclovir for 7­10 days ­ Treat per causes ­ Psoriasis: itchy erythema
scraping for microscopy and ­ No improvement: with white scales.
culture. refer to ­ Kaposi’s sarcoma
dermatologists  
­ Provide appropriate treatment
 

­ No improvement: biopsy for ­ Improved: complete ­ Symptomatic treatment in

histopathology, microscopy and the treatment collaboration with
culture dermatologist
­ Empirical treatment for the most ­ Not improved: refer
to dermatologist ­ Consider ARV treatment 
likely cause if has not been
treated before

 33
Instructions:
1. Causes of skin and mucosa lesions:

­ Bacterial infection: folliculitis, furuncles, cellulitis, TB­associated skin

lesions.
­ Viruses: Herpes simplex, Herpes zoster (Zona), Molluscum contagiosum
(poxvirus), human papiloma virus (HPV), oral hairy leukoplakia (Epstein­
Barr Virus)
­ Fungi: Candida, Penicillium, dermatophytes (ringworm, onychomycosis),
Cryptococcus,
­ Parasite: scabies
­ Neoplasms: Kaposi’s sarcoma, lymphoma
­ Other dermatitis: eosinophilic folliculitis, seborrheic dermatitis, pruritic
papular eruption (PPE), psoriasis, xerosis.
­ Drug reaction: Co­trimoxazol and ARVs can cause eruption, generalized
erythroderma, scalded or desquamated skin.
2. Considerations in taking history and examination:

History taking: Clinical examination:

­ Duration of illness? ­ Type of lesions: papule,
­ Where the lesions start? blister/vesicle, ulcer, maculae.

­ Itching present? ­ Distribution of rash

­ History of allergy such as asthma, ­ Evolution of lesions

weather­associated rash ­ Other manifestations of
­ Medications used? For how long? immunodeficiency, s. a. oral thrush,
cachexia
­ Accompanied symptoms such as
fever, etc. ­ Accompanied symptoms, s. a.
fever, hepatosplenomegaly,
neurological abnormalities

3. Etiological diagnosis and treatment: (See Section V “Diagnosis and

Treatment of common Opportunistic Infections”)

 34
9. Wasting (a, b)
­ Take history (c)

­ Do clinical examination

• Evidence of inadequate Odynophagia ± Fever, diarrhea or other

�
intake oral thrush constitutional symptoms
�
• Anxiety, depression
Treat for esophageal
• Try high level of protein and candidiasis
energy diet Give nutrition support
• Treat for depression

Investigate for OIs (e)

No improvement
­ Fever: Exclude TB, MAC (See
"Prolonged fever")

No causes found or no improvement:

• Re­evaluate, consider wasting • Definitive diagnosis
syndrome due to HIV (f)
• Appropriate treatment
• Consider ARV treatment
• Consider treatment with anabolic • Nutrition support
stimulators

 35
Instructions:
(a) Weight loss is defined by comparing the present and previous body weight
of the patient, if available, or estimated weight by height.

(b) Causes:
­ Infections: OIs such as TB, chronic diarrhea due to protozoan parasites,
systemic fungal infections and MAC
�
­ Malnutrition due to inadequate intake
�
­ Poor intake due to odynophagia (esophageal candidiasis)
�
­ Psychiatric conditions: anxiety, depression
�

(c) History taking:

­ Duration and grade of wasting
­ Symptoms such as fever, diarrhea, painful swallowing, cough, etc.
­ History of opportunistic infections
­ Nutrition
­ Manifestations of anxiety and depression

(d) Physical examination

­ Evaluate the severity of wasting, look for edema, anemia
�
­ Look for manifestations of OIs (oral thrush, enlarged lymph nodes, etc.)
�

(e) Analyses and investigations:

­ Chest X ray, sputum AFB if TB suspected
­ Blood culture if bacterial or fungal septicemia suspected
­ Stool examination for protozoas

(f) Wasting syndrome due to HIV:

­ Weight loss of more than 10% body weight
­ Accompanied by
­ chronic diarrhea (loose stool more than twice per day) for at least 30
days
�
­ or prolonged fever for at least 30 days
�
­ No any other explainable cause (e.g. TB, cancer) of these
manifestations found

 37
 V. DIAGNOSIS AND TREATMENT OF COMMON OPPORTUNISTIC INFECTIONS

Table 6: Diagnosis and treatment of common OIs

OI Clinical manifestations Diagnosis Treatment

1. Fungal diseases
Oral candidiasis: Multiple Diagnosis clinical Fluconazole 100­150 mg per day or
Candidiasis
creamy­white, easily removable
patches or Fungal microscopy and culture Ketoconazole 200 mg b.i.d for 7 days.
pseudomembraneous plaques should only be performed if clinical
on the tongue, gums, buccal manifestations are atypical or
mucosa, and palate, anterior treatment is ineffective
surface of tonsils, posterior wall
of throat.

Esophageal candidiasis: painful Diagnosis mainly clinical Fluconazole 200­300 mg/day x 14 days or
swallowing
Esophagoscopy if patient does not Itraconazole 400mg/day x 14 days or
improve after standard treatment
for candidal esophagitis Ketoconazole 200 mg b.i.d x 14 days

 38
 Vaginal candidiasis: Diagnosis mainly clinical Fungal Fluconazole 150­ 200 mg orally, single dose: higher
microscopy or culture if clinical dose and more prolonged duration of treatment in
Itching and burning sensation; features are atypical or treatment case of severe immunodeficiency; or:
creamy white vaginal discharge is ineffective.
with cheese­like plaques. Vulvo­ Itraconazole 100 mg orally, b.i.d x 3 consecutive
vaginal area is erythematous, days; or
swollen and painful. Recurrence
is common. Clotrimazole 100 mg or miconazole 100 mg as
vaginal suppositoria, 1suppositorium/day x 7 days,
or

Clotrimazole 500 mg single vaginal

suppositorium, or

Nystatin 100.000 units, 1 vaginal

suppositorium/day x 14 days

Cryptococcosi Fungal septicemia: fever, skin Skin biopsy or lymph node ­ Preferred regimen: amphotericin B IV
s papulewith necrosis, lung aspiration for fungi, blood culture 0.7mg/kg/day x 2 weeks, followed by fluconazole
infiltration, meningitis 800­ 900 mg/day x 8 weeks.
CSF analysis, India ink staining
­ Alternatives: fluconazole 800­ 900 mg/day x 8
Meningitis: headache, and culture for fungi
weeks (for mild and uncomplicated cases or when
photophobia, meningeal amphotericin B is unavailable).
syndrome, altered
Treatment of intracranial hypertension: Do daily
consciousness, focal
CSF drainage by repeated lumbar puncture with
neurological deficits, fever removal of 15­20 ml of CSF each time or until the
headache is relieved (mannitol and corticosteroids
are ineffective)..
Maintenance therapy: fluconazole 150­ 200
mg/day lifelong; discontinue when the patient is on
 39
 ART and has the CD4 count > 200 cells/mm3 of ≥
6 months

Penicilliniosis ­ Isolated skin lesions: umbilical ­ Based on typical clinical features.

­ Preferred regimen: amphotericin B (0.7 mg/day)
(Disease due papules with central dark for 2 weeks, then itraconazole 200 mg b.i.d x 8­ 10
necrotic crust, without itching or­ Microscopy and culture of skin weeks
to Penicillium scrapping, bone marrow and lymph
pain, limited to the face or
merneffei) node aspirations. ­ Alternatives (For mild cases or when
generalized.
Amphotericin B is unavailable): itraconazole 200
­ Fungal septicemia: fever, skin ­ Do culture of blood and above mg b.i.d x 8 weeks
lesions, anemia, mentioned specimens
o
in
hepatosplenomegaly, Sabouraud’s medium at 25­37 C. Maintenance therapy: itraconazole 200 mg/day
lymphadenopathy, cachexia. lifelong; discontinue when the patient is on ART
and has CD4 count > 200 cells/mm3 of ≥ 6
­ Fungal pneumonia: dry cough, months.
fever; mild to moderate dyspnea
may present. Must be
differentiated from miliary TB
and PCP

Co­trimoxazole: 15mg TMP/kg/day in 4 divided

Pneumocystis Cough, dyspnea, fever, night Diagnosis clinical
jiroveci sweat doses x 21 days; patients weighed < 40 kg: TMP­
Normal chest X ray in over 90% of SMX 480 mg, 2 tablets x 4 times/day; patients
pneumonia Subacute onset of symptoms patients; typical CXR: diffuse
(PCP) weighed > 40 kg: TMP­ SMX 480 mg, 3 tablets x 4
over 1­ 2 weeks bilateral interstitial infiltrations.
times/day.
Response to treatment trial with
co­ trimoxazole may be exploited In case of respiratory failure: prednisone (orally or
for diagnosis intravenously) 40mg x 2 times/day x 5 days, then
40mg x once daily x 5 days, then 20 mg x once
If available: aspirate
 40
 bronchioaveolar lavage fluid for daily x 11 days).
Giemsa or silver or
Maintenance therapy: Cotrimoxazole 960 mg
immunofluorescence staining for P.
jiroveci. orally daily until when the patient is on ART and
has CD4 count > 200 cells/mm3 of ≥ 6 months.

Alternatives: Clindamycin 600 mg IV or 450 mg

orally t.i.d + primaquine 15 mg orally once daily for
21 days in case of hypersensitivity to
sulphonamides

2. Protozoal diseases
Toxoplasmal Headache, drowsiness, Focal neurological signs Co­trimoxazole: TMP based dosage is 10
encephalitis seizures, focal neurological mg/kg/day intravenously or orally for 3­6 weeks or
deficits Single or multiple mass­occupied
lesions on brain CT or MRI (if Pyrimethamine (200 mg loading dose, then 50­75
Fever available). mg once daily) + sulfadiazine (2­4g/initial dose,
then 1­ 1.5 g every 6 hours) for 3­6 weeks.
Response to presumptive
treatment can be used to support Maintenance therapy: Pyrimethamine (25­50
the diagnosis mg/day) + Sulfadiazine (1g x every 6 hours);
discontinue when the patient is on ART with CD4
count > 100 cells/mm3 of ≥ 6 months.

Protozoal Chronic diarrhea Stool examination for parasites ART is the best treatment
diarrhea
(Cryptosporidi Vomiting, abdominal pain Diarrhea due to Microsporidia and Isospora can
um, be responsive to Albendazole 400 mg b.i.d x 3
Microsporidia weeks and Co­trimoxazole 960mg b.i.d x 10 days

 41
Isospora)

3. Bacterial diseases
Mycobacteriu Prolonged or recurrent fever, Isolation of MAC from blood or Preferred regimen: oral clarithromycin 500mg b.i.d
m avium weight loss, fatigue, anemia, other sites, usually difficult to + ethambutol 15mg/kg/day.
complex hepatosplenomegaly and perform.
(MAC) lymphadenopathy. Do Alternative regimen: oral azithromycin 500mg/day
differential diagnosis withTB. + ethambutol ± rifabutin 300mg/day; or
azithromycin 500mg/day + ethambutol or
Consider diagnosis of MAC if the ciprofloxacin 500mg x twice per day.
patient is not responsive to TB
treatment after 2­4 weeks. ART must be given.

Discontinue treatment only if the patient is on ART

and CD4 count > 100 cells/mm3for more than 6
months.

Purulent ­ Causative microorganisms: ­ Treatment depends on severity of the disease:

­ Clinical diagnosis;
polymyositis Staphylococcus aureus, antibiotics oral for mild, and parenteral for severe
Streptococci; more common in ­ Microscopy and culture of the cases. Choose antibiotics, which are active to
IDUs pus for bacteria if available staphylococci, streptococci, such as oxacillin, first
generation of cephalosporin (cephalothin,
­ Clinical manifestations: cephazolin, etc.), and other antibiotics.
pyoderma, folliculitis, cellulitis,
abscess of muscle and soft ­ Topical cleaning and wound hygiene in cases of
tissues, with or without fever; ulcers. Use anti­inflammatory and proteolytic
systemic and other organs agents.
involvement.

Pneumonia ­ Causative bacteria: Characteristic clinical features. Intravenous 3rd generation cephalosporins

 42
and pleuritis pneumococcus, staphylococcus, Investigations: elevated WBC and (cefotaxime, ceftriaxone); anti­staphylococcal
H. influenzae, P. aeruginosae, neutrophils; antibiotics if pneumonia due to staphylococcus;
S. aureus, etc.; rare: R. equi, anti­pseudomonas antibiotics if the patient having
Nocardia species; Chest X ray a history of pseudomonas disease or in severe
Sputum microscopy and culture, immunocompromised stage; co­trimoxazole in
­ Clinical features: abrupt onset case of Nocardia disease (nocardiosis), etc..
with fever, chills, chest pain, blood culture, thoracentesis for
productive cough with thick bacterial microscopy and culture if
sputum; dyspnea may present; applicable;
examination may reveal lung
consolidation or pleural effusion,
lung crackles;

Bacterial ­ Causative bacteria: Diagnosis based on clinical Empirical treatment with ceftriaxone intravenously
meningitis pneumococcus, other bacteria manifestations; 3­4g/day; modify the treatment according to
including rare pathogens such bacterial culture and results of antimicrobial
as R.equi, Chryseobacterium Lumbar puncture, CSF susceptibility testing. If no bacteria isolated,
meningosepticum, etc. biochemistry, cytology, microscopy choose antibiotics on etiological judgment based
and culture, on clinical manifestations.
­ Clinical features: abrupt or
subacute onset, fever, Blood culture if possible;
headache, meningeal signs; Brain CT scan if available and
brain abscess may develop. brain abscess is suspected

Septicemia ­ Bacterial causes: Salmonella Diagnosis on basis of clinical

­ Empirical treatment based on suggestive
species, S. aureus, E.coli, manifestations and blood culture if
clinical findings [antibiotics active against Gram
Proteus mirabilis, Serratia available [some bacteria require
(­) bacteria for patients with fever and diarrhea;
marcescens, P. aeruginosae, special media or prolonged
antibiotics active against staphylococcus for

 43
 R.equi, and other bacteria incubation time (nocardia)]; IDUs with cellulitis and pneumonia, etc.].
Modify antibiotic treatment according to
­ Clinical manifestations: fever, Chest X ray or ultrasound if septic isolated bacteria and results of antimicrobial
chills, diarrhea (Salmonella metastases suspected (in lung, susceptibility testing.
species, E.coli), cellulitis (S. liver, spleen, etc.);
aureus), abscess in the lung and
other organs (S. aureus, R.equi, Aspirate of metastatic sites
Nocardia species, P. (abscess in soft tissues or internal
aeruginosa), meningitis and/or organs, meningis) for microscopy
brain abscess (R.equi), etc. and culture for causative bacteria.

Bacterial ­ Bacteria: Salmonella, Shigella, − Stool microscopy shows RBC ­ Bacteria can be isolated: treatment according the
diarrhea Campylobacter and other and/or WBC (invasive diarrhea) results of antimicrobial susceptibility testing
enteric bacteria ­ Bacteria cannot be isolated: treat empirically with
− Culture of blood, stool or fluids
­ Clinical features: fever, from metastatic foci ciprofloxacin or another new fluoroquinolone.
frequent bowel movements Monitor the response to treatment (fever, diarrhea)
with watery or bloody
mucous stools; colics and
tenesmus may present. The
diarrhea is often severe, and
has prolonged course and
frequently accompanied with
septicemia; septic metastatic
foci may present in lungs,
joints, hepatobiliary tract and
bone marrow.

 44
4. Viral diseases
Herpes Clusters of typical blisters, Typical clinical appearance Acyclovir 200 5 times (or 400 mg t.i.d) daily for 7
simplex usually in genital area or face. days
Systemic involvement (HSV Local care with gentian violet or chlorhexidine.
encephalitis) is possible

Herpes zoster Typical painful blisters in Typical clinical appearance Acyclovir 800 mg 5 times daily for 7 days
clusters within a dermatome. Local care with gentian violet or chlorhexidine.
Eye can be involved
Ophthalmic herpes zoster: acyclovir eye ointment

Cytomegalo­ ­ Retinitis: blurred vision, with Retinitis: clinical diagnosis based − Acute phase:
virus (CMV) floating dark spots, scotoma, on fundoscopy. + Intraocular ganciclovir, 2 mg in 0.05­0.1 ml twice
photophobia, progressing to Retinal lesions: discrete or diffuse a week for 3 weeks, then maintenance therapy
retinal detachment and patches of retinal necrosis (white) once a week. Collaboration with ophthalmologists
blindness if not treated timely. with or without hemorrhage. is adviced.
May affect one side, or spread
Diagnosis of other CMV­related + Ganciclovir intravenously 7.5 ­10 mg/kg/day in 2
to the other side. Retinal lesions
conditions should be based on divided doses for 21 days or longer if no response
are irreversible.
biopsy and viral culture or PCR of Following drugs can be used if available:
­ Colitis. specimens from infected sites,
­ Esophagitis such as brain, CSF, skin craping, + Foscarnet 60 mg/kg/every 8 hours, and if
blood, if available. effective, continue with 60­120mg/kg/day.
­ Gastritis
+ Valganciclovir 900mg orally b.i.d x 21 days; or
­ Encephalitis
+ Valganciclovir intraocular every 6 months +
­ Polyradiculopathy ganciclovir IV or valganciclovir orally as above
­ Skin lesions.
− Ganciclovir intraocular implant every 6 months
Maintenance treatment: Ganciclovir 5mg/kg/day
 45
 every day, or 6mg/kg/day for 5 days per week; or
Valganciclovir orally 900mg/day, or Foscarnet 90­
120mg/kg IV daily; or Ganciclovir intraocular
implant every 6­9 months + ganciclovir 1­1.5g
orally 3 times/day
Consider discontinuation of treatment when CD4
count > 100 cells/mm3.
Other diseases caused by CMV: similar treatment
with above medications.
Molluscum Pedunculated nodular lesions, Clinically Removal by enucleating or cryotherapy, prick the
contagiosum usually on face, genital area and centre and apply phenol.
neck, armpits Responsive to ART
Genital warts Manifestation: Warts present as Mainly relied on clinical features. ­ Consultation with Dermatologist. Topical
(HPV) soft, moist, pink, cauliflower­like treatment under specialized supervision with
papules with peduncle, painless podophyllin, trichloroacetic acid; cryotherapy with
and easily bleeding. liquid nitrogen, carbonic laser or electrosurgery.
­ In men warts are found most ­ Responsive to ART
frequently at the coronal sulcus,
prepuce and penis shaft and
occasionally at urethral meatus.
­ In women, warts often occur at
clitoris, minor labia, around
urethral meatus, perineum.
­ Genital HPV infection
increases the risk of genital
cancer.
*Pay attention to interaction between OI drugs and ARVs (see Annex 5)
 46
5. Diagnosis and treatment of TB in patients with HIV/AIDS

The management of patients with TB/HIV co­infection is implemented

according to the “Protocol for Collaboration in diagnosis, treatment and
management of TB/HIV co­infected patients” promulgated in Decision
No.3116/Qð­BYT dated August 21, 2007 of the Minister of Health.

5.1. Diagnosis of TB
5.1.1. TB screening:
HIV infected people must be asked for symptoms suggestive of TB at all visits
to health care facilities, including:
­ Productive cough, possibly hemoptysis
­ Prolonged fever.
­ Wasting
­ Night sweating.
Suspected TB subjects must be screened for pulmonary and extrapulmonary
TB by clinical assessment, chest x ray and sputum AFB.

5.1.2. Diagnosis of pulmonary TB

5.1.2.1. Diagnosis of smear positive pulmonary TB
HIV infected people with at least 1 AFB positive sputum smear are considered
smear positive pulmonary TB and should be registered and treated as soon as
possible (diagnosis protocol)
5.1.2.2. Diagnosis of smear negative pulmonary TB
Smear negative pulmonary TB in HIV infected people is defined according to
diagnosis procedure and must fulfill following criteria: ≥ 2 sputum negative
smears for AFB, chest x ray suggestive for active TB and the decision of
a specialist.

 47
 Diagram 1: Diagnosis procedure of pulmonary TB in HIV infected patients
�

PEOPLE WITH HIV (+) SUSPECTED TB and NO DANGER SIGNS a

Sputum smear for AFB

Chest X ray

AFB positive b AFB negative c

Treat for TB, CPT Probable TB Sputum AFB and culture e

HIV assessment d Clinical assessment, CXR

TB Unlikely

Treat for PCP Broad­spectrum antibiotics g

�
HIV assessment d CPT d, HIV assessment d
�

Improved h No/partial improvement Improved h

Re­assess for TB

Note:
�

a The patient at presentation is not with dangerous signs (able to walk, no dyspnea,
no high fever, pulse less than 120 bpm).

b AFB positive pulmonary TB is defined as at least one positive smear,

c AFB negative is defined as at least two sputum negative smears.

d HIV assessment includes: clinical staging, determination of CD4 count and

referral for HIV/AIDS care (including ART).

e Only some facilities can do culture for M.tuberculosis.

f It is best to compare the chest X­ray images with the ones from previous visits
(e.g. X ray film from the first visit). The patient should be carefully assessed
clinically and have chest x ray done to confirm or exclude the diagnosis.

g Broad­spectrum antibiotics except fluoroquinolones.

 48
h � Re­assess according to the procedure if symptoms reappear.

Diagram 2: Diagnosis procedure of pulmonary TB in severe patients with

HIV infection
HIV (+) PATIENTS WITH SUSPECTED TB and DANGER SIGNS a

Refer to a higher level Immediate referral not possible

Parenteral broad­spectrum antibiotics b

� Parenteral broad­spectrum
Sputum AFB and culture
� antibiotics bTreat for PCP
Chest X ray c
� Sputum AFB, Chest X ray c

No TB TB AFB positive d AFB negative d

Improved after 3­ Not improved

Care and treat for TB/HIV
5 days after 3­5 days

Re­evaluate HIV Unlikely to Evaluate the Start TB treatment

associated have TB likelihood of TB Stop antibiotics
diseases diagnosis e Refer for HIV and TB
care and treatment

Note:

a � The danger signs include one of the followings: respiratory rate >30
breaths/minute, fever >39oC, pulse rate >120 beats/minute and unable to walk.

b � Broad­spectrum antibiotics except fluoroquinolones.

c � These investigations must be done early to speed up the diagnosis.

d � AFB positive is defined as at least one smear positive and AFB negative as two or
more negative smears.

e � Re­assessment for TB includes AFB examination and clinical evaluation.

5.1.3. Diagnosis of extra pulmonary TB

 49
 Diagnosis is based on:

­ Positive smear for acid­fast bacilli (AFB) or positive culture for

Mycobacterium tuberculosis with an extra pulmonary specimen

or

­ Histological or clinical evidence consistent with diagnosis of progressive

extra pulmonary TB and is confirmed by a decision of a specialist.

 50
 Table 7: Summarized table assistant for diagnosis of common extra pulmonary TB in people with HIV infection

LYMPHNODE TB PLEURAL EFFUSION DISSEMINATED

PERICARDIAL EFFUSION TUBERCULOUS MENINGITIS
(PERIPHERAL) TUBERCULOSIS

Suspect TB if Suspect TB if Suspect TB if Suspect TB if Suspect TB if

• 2 cm or more in size • Unilateral effusion • Weight loss, fever and • Weight loss, night sweats, fever • Weight loss, night sweats, fever
cough
• Asymmetric • Pleural fluid is clear and • Evidence of TB elsewhere • Clear CSF with elevated
straw colored • Abnormal chest x ray protein, low glucose and
• Painless swelling (possibly miliary pattern) • Lung fields clear both sides (bilateral lymphocytosis
Findings that suggest pleural effusion may present);
• Firm/fluctuant/ non TB diagnosis • Hepatosplenomegaly symmetrical enlarged heart shape • Cryptococcal antigen (or India
fistulated ink stain and culture) negative in
• Bilateral effusion • Night sweats Findings that suggest non TB CSF
• Cervical location (possibly heart failure or diagnosis
pneumonia) • Anemia • Evidence of TB in elsewhere
• Weight loss, night • Streaky shadowing in the lungs or
sweats, fever • Clinical malignancy Findings that suggest non heart shape not symmetrical Findings that suggest non TB
TB diagnosis (possibly heart failure) diagnosis
Findings that suggest • Cloudy/purulent pleural
non TB diagnosis fluid (possible • Consider Salmonella, • Hypertension • CSF cloudy or neutrophils
empyema) pneumococcus, malaria, present on microscopy (possibly
• Symmetrical cryptoccocus • Electrocardiogram suggests other bacterial meningitis)
(lymphoma or HIV • Blood colored fluid causes of cardiomegaly
associated • Fever with rigor (hypertension, coronary disease, • Cryptoccocal tests (+)
lymphadenopathy) Essential investigations valvular diseases, myocardiopathy,
• Tachypnea (respiratory • Rapid onset
etc.)
• Tender, inflamed, • Chest X ray rate over 30 bpm)
purulent (bacterial or • Fever with rigor (pericarditis with • High opening pressure of CSF
fungal) • Sputum smear for AFB • Severe diarrhea (possibly cryptococcus)
Gram (­) bacteria)
if coughing
• Site other than • Bloody stool Essential investigations Essential investigations
•Fluid aspirate and analysis

 51
 cervical (biochemistry, cytology) Essential investigations • Chest X ray • Lumbar punture

Essential investigations •Pleura biopsy and • Chest X ray • Sputum smear for AFB if coughing • CSF microscopy (Gram stain
pleuroscopy if needed and AFB), CSF protein and
• Sputum smears if • Malaria smear • Electrocardiography (if ultrasound not glucose
coughing Immediate management available)
• Sputum smear for AFB • Cryptococcal antigen and stain
• Needle aspirate for Features of TB only • Echocardiography (ideally)
cytology and AFB • Blood culture, complete • Sputum smear for AFB if
• Start TB treatment blood count and Immediate management coughing
Immediate management cryptococcal antigen
Non TB features Features of TB only Immediate management
• Aspirate for cytology Immediate management
and AFB microscopy • Look for other causes • Start TB treatment Features of TB only
Features of TB only
• Lymphnode biopsy if • Straw fluid without other • Refer for urgent aspiration if very • Admit to hospital
needed diagnosis after 7 days • Start TB treatment (+ breathless/unwell
→ treat as TB antibiotics if critically ill) • Start TB treatment
Non TB features
Non TB features Features of non­ TB diagnosis
• Investigate other causes Start TB
• Investigate other causes treatment if pericardial effusion is Treat for cryptococcosis if tests for
confirmed by ultrasound and no other cryptococcus (+) or no other
• Start both TB treatment diagnosis by 7 days. diagnosis made
and antibiotics if the
patient is critically ill
(“surrounding”)

 52
5.2. Treatment of tuberculosis
­ People with HIV infection should be registered and treated for TB as soon
as possible after TB diagnosis.
­ TB treatment follows National Guidelines of TB Program, similar for HIV (­)
TB patients.
­ Provide cotrimoxazole prophylaxis to prevent other opportunistic infections.
ART should be considered early and attention should be paid to drug
interaction between ARVs and rifampicin, INH .
5.2.1. Essential anti­TB drugs (first line):
�
National TB Program defines five essential anti TB drugs as follows: Isoniazid
�
(INH), Rifampicin (RMP), Pyrazinamid (PZA), Streptomycin (SM) and
�
Ethambutol (EMB).
�
5.2.2. Indications of anti­TB regimens:
�
Regimen I: 2S(E)HRZ/6HE or 2S(E)RHZ/4RH (applied only if direct
�
observation continued in maintenance phase): Intensive phase lasts for 2
�
months with 4 daily drugs, of which E can substitute for S. Maintenance phase
�
lasts for 6 months with 2 drugs H and E given daily or for 4 months with 2
�
drugs R and H given daily.
�
Indications: for newly diagnosed TB cases (never been treated for TB
or ever been treated for TB but duration last for less than one month)

Regimen II: 2SRHZE/1RHZE/5R3H3E3: Intensive phase lasts for 3 months, of

which the first 2 months are with 5 essential drugs given daily (SHRZE),
followed by 1 month with 4 drugs (HRZE) given daily. Maintenance phase lasts
for 5 months with 3 drugs H, R and E given 3 times per week.
Indications: for cases with recurrence of TB and failure of regimen I, re­
treatment after selfdiscontinuation, some severe forms of TB and others
special forms of TB (classified according treatment history).

Regimen III: 2HRZE/4HR or 2HRZ/4HR: Intensive phase lasts for 2 months

with 4 drugs (HRZE) or 3 drugs (HRZ) given daily, for all TB forms in children.
Maintenance phase lasts for 4 months with 2 drugs H and R given daily.
Indications: for pediatric TB cases. In severe forms in children,
combination with S can be considered.

 53

VI. ANTIRETROVIRAL THERAPY (ART)

1. Goals and Principles of Antiretroviral Therapy

1.1. Goals of Antiretroviral Therapy:

­ To inhibit viral replication and maintain the viral load at the possible lowest
level in the blood.
­ To restore immune function and reduce the risk of opportunistic infections
(OI).
­ To improve the quality of life and the survival of people living with HIV/AIDS
(PLWHA).
1.2. Principles of Antiretroviral Therapy:
− ART is one part of a comprehensive package of medical care and
psychosocial support services for people living with HIV/AIDS.
− ART is primarily provided on outpatient basis and is given only when
patients are clinically and/or immunologically eligible and ready to adhere to
treatment.
− Any ART regimen must include at least 3 drugs. Antiretroviral therapy is
lifelong and the patients must completely adhere to therapy to ensure the
effectiveness of treatment and prevent the emergence of drug resistance.
− People with HIV infection commencing ART must continue to apply
measures to prevent the transmission of the virus to others.
− People with HIV infection commencing ART must receive prophylaxis of
opportunistic infections until their immune system has been reconstituted.
1.3. ARV drug classes available for use in Viet Nam:
− Nucleoside and nucleotide reverse transcriptase inhibitors (NRTIs)
− Non­nucleoside revese transcriptase inhibitors (NNRTIs)
− Protease inhibitors (PIs)
(See Details of common ARV drugs in Annex 4)
2. Criteria for initiating Antiretroviral Therapy

Antiretroviral Therapy is initiated on the basis of clinical staging and CD4 cell
count

If CD4 cell count available, ART is indicated when:

­ Patients with Clinical stage 4 irrespective of CD4 cell count

 54

 ­ Patients with Clinical stage 3 and CD4 cell count < 350 cells/mm3
­ Patients with Clinical stage 1 or 2 and CD4 cell count < 250
cells/mm3

If CD4 cell count not available, start ART for HIV­infected patients at
clinical stage 3 or 4.
3. Preparation for readiness to commence Antiretroviral Therapy

The preparation for readiness to commence ART must be started from

the time the patients first present to the treatment facility. The contents of the
readiness preparation should proceed at every patients'visit so that the ART
can be initiated immediately should the patients fulfill the criteria for initiating
the treatment.
3.1. Pre­ART assessment:
The following is the content of the Pre­ART assessment for the patients
who fulfill the clinical and/or immunological criteria for initiating ART:
­ Record the pre­treatment cClinical stage and the CD4 cell count (if
available)
­ Screen for TB and other OIs; provide treatment for TB and acute OIs, if
present; collaborate with other healthcare services (e.g. antituberculosis,
obstetric and gynecology, etc.) if needed.
­ Perform basic laboratory tests and those necessary for selecting ART
regimens, such as full blood count/Hb and liver function test (ALT); screen
for HBsAg and anti­HCV, if possible.
­ Take history of previous ART, if any, the reason for use, the facility
provided, actual regimen taken; pay attention to use of suboptimal
regimens (such as dual ARV regimen), the adherence to therapy, and the
course of disease with the treatment.
­ Assess the willingness of the patient to be treated and the availability of the
treatment supporter
­ choose the suitable ARV regimen for the patient, consider drug interactions
between ARVs and OI drugs and other drugs (see Annex 6)
­ Inform the patient about the plan for ART­readiness preparation
­ Provide Co­trimoxazole prophylaxis, other prophylaxis if indicated and
available.
3.2. Education and counseling on adherence to Antiretroviral Therapy

 55

­ Provide group counseling and education on the course of HIV infection,

prevention of HIV transmission, positive living, nutrition and ART, then
individual counseling and education. Each patient should receive 3
counseling and education sessions prior to ARV treatment.
­ Provide detail individual counseling on ARV treatment, each patient's
regimen, the importance of treatment adherence, plan for adherence
support, management of the problems that occur during treatment (e.g.
missing a dose, side effects, etc.).
­ Provide appropriate counseling for drug users, pregnant women.
3.3. Assessment for treatment readiness
­ Assess the patients’ understanding about HIV infection, antiretroviral
therapy, and the importance of adherence to treatment, what to do when
missing a dose.
­ Assess the patients’ understanding of how to use the drugs, common side
effects and its and their management.
­ Assess the patients’ ability to adhere to treatment by how regularly they
attend the counseling sessions and follow­up visits, how well they adhere to
co­trimoxazole prophylaxis. Each patient must also have a treatment
adherence plan (such as drug taking schedule, reminders for taking doses,
availability of treatment supporter), and are willing and commit to participate
in treatment program.
­ Check other information, such as place of residency, ability to contact when
needed.
� If the patients fulfill the criteria for treatment readiness, start antiretroviral
therapy.
Note:

If the patients are in severe clinical conditions (clinical stage 4 or CD4<100

cells/mm3), or the patient is pregnant:shorten the preparation period;
provide adherence counseling to the treatment supporters and/or the
patients themselves in subsequent visits or when the patient’s condition
stabilizes.
3.4. Initiation of Antiretroviral Therapy
­ Review the patients on how to take the drugs, theschedule of drug
dispensing and follow­up visits; ensure that patients have a plan to comply
with therapy and know how to manage if facing difficulties.

 56

­ Prescribe a first­line regimen for HIV­infected patients newly starting

antiretroviral therapy;
­ For patients with previous history of commencing ART or ART interruption,
assess the clinical condition and laboratory parameters to decide
appropriate first­line regimen or a second­line regimen in case of treatment
failure.

4. First­line Antiretroviral Regimens:

4.1. Prioritized regimens:

AZT + 3TC + NVP

Or
d4T + 3TC + NVP

Indication: Use one of these regimens for all patients starting ART
a. AZT + 3TC + NVP
Dose:
− AZT 300 mg twice daily
− 3TC 150 mg twice daily
− NVP 200mg once daily during the first 2 weeks, then 200mg twice daily
Take the drugs every 12 hours. No diet restrictions required.
Measure Hgb and ALT before starting ART, after 1 month and then every 6
months, and whenever anemia or hepatitis is suspected.
Do not start AZT containing regiment if patients’ Hb < 80 g/l. ,Use NVP
containing regimen with caution in patients’ with ALT > 2,5 upper normal limit,
women with CD4 >250 cells/mm3 and in patient on TB therapy with rifampicin
b. d4T + 3TC + NVP regimen
Usual adult dose:
− d4T 30 mg twice daily
− 3TC 150 mg twice daily
− NVP 200mg once daily in the first 2 weeks, then twice daily
Take the drugs every 12 hours. No diet restrictions required
Measure ALT before starting ART, after 1 month and then every 6 months
 57

Use NVP containing regimen with caution in patients’ with ALT > 2,5 upper
normal limit, women with CD4 >250 cells/mm3 and in patients on TB therapy
with rifampicin

4.2. Alternative regimens:

4.2.1. AZT + 3TC + EFV or d4T + 3TC + EFV regimen:
Indication: Use one of these regimens if patients cannot use NVP
a. AZT + 3TC + EFV
Normal adult dose:
­ AZT 300 mg twice daily
­ 3TC 150 mg twice daily
­ EFV 600 mg once daily at night
Take AZT + 3TC every 12 hours and EFV at night. Do not take EFV with fatty
meal
�
Measure Hgb before starting ART, after 1 month and then every 6 months,
�
and whenever anemia is suspected.
�
Do not start AZT containing regiment if patients’ Hb < 80 g/l and/or Do not start
�
EFV based regimen for pregnant women during the first trimester.
�
Avoid using EFV in patients with serious psychiatric problems (current or in
�
the past)
�

b. d4T + 3TC + EFV

DNormal adult dose:
­ d4T 30 mg twice daily
­ 3TC 150 mg twice daily
­ EFV 600 mg once daily at night
Take d4T + 3TC every 12 hours and EFV at night. Do not take EFV with fatty
meal
�
Do not start EFV based regimen for pregnant women during the first trimester.
�
Avoid using EFV in patients with serious psychiatric problems (current or in
�
the past)
�
4.2.2. TDF + 3TC+ NVP or TDF + 3TC+ EFV regimen

 58

Indication: this combination is the optimal for patients who cannot use both
AZT and d4T.
a. TDF + 3TC+ NVP
DNormal adult dose
� 3TC, NVP: as above.
� TDF: 300 mg once daily.
Note: Measure creatinin/creatinin clearance test prior to ART and every 6
months, change dose when patient has renal failure.

Creatinine Clearance (ML/min) and TDF dose

>50ml/min 30 – 49 ml/min 10 – 29 ml/min <10 ml/min

Once daily TDF 300mg every TDF 300mg every Contra­indication

other day 3­ 4 days or twice
TDF 300mg
a week

b. TDF + 3TC+ EFV

DNormal adult dose and usage:
� 3TC, EFV: as above.
� TDF: 300 mg once daily.
Note: Measure creatinin/creatinine clearance test prior to ART and every 6
months, change dose when patient has renal failure (as mentioned above)
4.2.3. AZT + 3TC + TDF
Indication: this combination is the optimal for patients who cannot use either
�
NVP and EFV.
�
DNormal adult dose and usage:
�
� AZT, 3TC: as above.
� TDF: 300 mg once daily.
Note: Measure creatinin/reatinin clearance test prior to ART and every 6
months, change dose when patient has renal failure. Measure Hgb test prior to

 59

ART, after 1 month and then every 6 months, and whenever anemia is
suspected.

5. Side effects of ARVs drugs and its management:

See ARV related toxicity grading and its management in Annex 6):
5.1. �Mild side effects: often occur early after starting ART and self­resolve
with the time.
Table 13: Mild side effects of ARV and their management

Symptoms Management

Nausea Take drugs with meals

Diarrhea Give water and electrolyte replacement. Antidiarrheals such as

loperamide can provide temporary relief.

Headache Use paracetamol. If headache continues for 2 weeks patients

should see the doctors.

Fatigue Commonly lasts for 4­6 weeks, if longer, patients should see
the doctors.

Abdominal If constant, patients should see the doctors.

discomfort

Mild rash Use anti­histamine. If rash becomes more severe, consider

drug hypersensitivity.

Sleepiness Take drug before going to bed

Insomnia Supportive drugs can be used. If patients have severe EFV­

related insomnia, the drug can be taken in the morning and
avoid driving motorbike or operate machines.

Nightmare, Often happens when taking EFV, commonly not lasting for
dizziness longer than 3 weeks.

5.2. Management of major toxicity of first­line ARV drugs:

5.2.1. AZT related anemia

­ Anemia commonly occurs during the first 4­6 weeks of using AZT.

 60

­ Exclude other causes of anemia or leucopenia.

�

­ Determine anemia grades and manage:

�

Grade Hgb Management

Continue with AZT.

Grade 1 (Mild) 80 – 94 g/l
Supplement with micronutrients, such as
vitamin B12, iron and folic acid, counsel
on appropriate food intake.
70 – 79 g/l
Grade 2 (Moderate) Do CBC after 1 and 3 months. If patients’
condition is stable or improved, continue
with AZT and counsel patients on
appropriate food intake.

65 – 69 g/l Substitute AZT by d4T after excluding

Grade 3 (Severe) other causes which can result in anemia
or marrow suppression.

Transfuse red packed cells or whole

Grade 4 (Severe life <65 g/l blood.
threatening)
Supplement with micro nutrients, such as
vitamin B12, iron and folic acid,

5.2.2. NVP hypersensitivity

­ NVP hypersensitivity rash often occurs 2­8 weeks after starting ART:

­ Monitor patients closely and assess rash severity. Health care workers
should counsel patients to go to the clinic immediately if rash is getting
more serious or iffever, fatigue present

­ Give symptomatic management, use anti­ histamin or steroid depending on

the severity of rash; monitor closely clinical progress & ALT test

­ Management of ART is as follow, depending on the severity of rash:

Grade Manifestation Management

Grade 1 Erythema without other Continue with NVP, delay escalating

(Mild) symptoms dose for several days until rash is

 61

Grade 2 Diffuse maculopapular or improved (NVP 200mg/day should not

localized dry be used over 3 weeks).
(Moderate) desquamation

Grade 3 Diffuse erythema over STOPT NVP immediately. Continue

body or vesiculation or with other 2 drugs for 7 days, then
(Severe) moist desquamation replace NVP by EFV if the rash
improves or

If after 7 days, rash does not completely

improve, other 2 drugs should be also
stopped. Restart with EFV based
regimen when the patient is completely
stabilized.

Grade 4 Mucous membrane STOPT ALL 3 DRUGS immediately.

involvement in orifices,
(Severe life Hospitalize or refer to higher level
threatening) Steven Johnson syndrome
Restart ARV when the patients are
Erythema multiforme completely stabilized. Replace NVP by
EFV or TDF or LPV/r

5.2.3. NVP Hepatoxicity

­ Measure ALT before starting ART.Screen for HbsAg and anti­HCV if

possible.

­ Signs of NVP related hepatoxicity during ART include increase in ALT, with
or without clinical symptoms, such as rash, fever, fatigue, nausea, vomiting,
jaundice, abdominal pain. These signs commonly occur after starting ART
several weeks to months.

­ High risk of getting hepatoxicity has been observed in: (1) Pregnant women
with CD4 >250 /mm3, (2) patients with high ALT level before starting ART,
(3) patients with hepatitis B or C co­infection and (4) patients on TB
treatment with rifampicin

­ Closely monitor liver function tests for patients using NVP, especially those
with higher risks mentioned above.

­ Hepatoxicity grading and management:

Grade ALT Management

Grade 1(Mild) 1.25 ­ 2.50 times Continue with NVP.

higher upper normal
 62

 limit Monitor ALT closely in every 2 weeks

Grade 2 2.60 – 5 times higher

upper normal limit
(Moderate)

Grade 3 5 ­ 10 times higher STOPT NVP immediately. Continue

upper normal limit with other 2 drugs for 7 days, then
(Severe) replace NVP by EFV if ALT improves or

If ALT is not improved, stop other 2

drugs. Restart ART only when ALT has
been improved; replace NVP with EFV
based regimen.

Grade 4 > 10 times higher Take into account both ALT and clinical
upper normal limit signs and symptoms for appropriate
(Severe life management
threatening)
The ARV regimen can be stopped,
patient hospitalized or refered to higher
level.

Restart ART with NVP substituted with

EFV or TDF or LPV/r on case by case
basis

5.2.4. d4T­ related peripheral neuropathy

­ d4T related to peripheral neuropathy can occur after staring ART 3­12
months, usually after 6 months.

­ Signs and symptoms of peripheral neuropathy include numbness, tingling,

burning, pain, losing sensitivity, usually starting from distal parts of the
limbs (mainly at lower limbs, starting from toes); if severe, patients may
experience difficulties in movement, lost of sensitivity in many parts of the
body. In most of the cases, neuropathy symptoms persist permanently.

­ Asking patients and assess at each visit changes in tendon reflexes,

decrease peripheral sensation, neuropathy­related dystrophy for early
detection of peripheral neuropathy.

­ Replace d4T by AZT after 12 months from starting ART if possible, or

replace d4T by AZT or TDF whenever patient presents with
manifestations of peripheral neuropathy.
 63

­ When patients on d4T based regimen have signs of peripheral neuropathy,

health care workers need to:

• Check if patients are using other neurotoxic drugs. If patients are on

isonazid, ensure that patients are taking pyridoxine 50mg (vitamin B6)
daily; DO NOT STOP isonazid.

• If possible, stop other neurotoxic drugs .

5.2.5. Lipodystrophy

­ , Lipoatrophy and lipodystrophy are most commonly associated with NRTIs,

especially d4T; usually occur after starting ART 6­12 months or longer.

­ Manifestations: loss of subcutaneous fat in the face, arms, legs, buttocks

with/without central fat accumulation in abdomen, viscera, breast, neck
(often irreversible). If severe, it can cause metabolic disorder such as
hyperlipidemia or diabetesmellitus.

­ Management:

• Monitor closely signs of lipoatrophy.

• Monitor blood glucose and lipid

• Replace d4T by AZT after 12 months from starting ART if possible,

or replace d4T by AZT or TDF whenever patient presents with
manifestations of lipodistrophy.

5.2.6. Other toxicities of first­line ARVs and management

ARV
Management
drug Common associated toxicity

Give lower dose if patient has renal

failure. Replace TDF by
Renal toxicity
TDF AZT or ABC or d4T.
affects bone growth
Avoid using TDF for pregnant
woman and children.

Persistent and severe central Replace EFV by NVP, TDF or

EFV
nervous LPV/r

 64

 system toxicity

gynecomasty can be seen in man

Manage as as with NVP

Rash or hepatoxicity hepatotoxicity. If grade 3, 4: replace
EFV by TDF or LPV/r

Do not use EFV for pregnant

women during the first trimester of
Potential teratogenicity
pregnancy (see section on use of
antiretrovirals in pregnant women)

Lactate acidosis: slow progress with

non­specific symptoms, such as Discontinue ART
fatigue, , difficult breathing, Hospitalize the patient.
abdominal pain, nausea, vomiting, Restart ART when patients
,lost appetite, weight loss,; completely recovered. Replacing
Analyses: increased level of lactic d4T by TDF
d4T acid, ALT, CPK, LDH, and anion
gap

Discontinue ART; provide

Acute pancreatitis: Abdominal pain, supportive treatment and laboratory
nausea, vomiting, fever, increased monitoring. Restart ART with
amylasemia. another drug with a lower risk of
pancreatic toxicity, such as AZT,
TDF, ABC.

6. Monitoring of Antiretroviral Therapy

­ Patients initiating ART should be followed and have drugs dispensed

according the schedule.

­ Frequent follow­up visits should be encouraged at the start of ART for

more counseling, adherence support and drug toxicity monitoring.

­ When patients adhere well to treatment, tolerate the prescribed regimen,

and the clinical symptoms improved, the time frequency of follow­up visits
and drug dispensary is once a month; for some cases with specific
situations, if patients adhere and respond well to treatment, 2­month follow­
up visits can be proposed with the agreement of the care and treatment
team. More frequent follow­up schedule is needed if patients develop new
OIs, experience drug side effects and , need modification of the regimens
or in case patients do not comply with therapy. .

 65

­ At each follow­up visit, patients are evaluated for clinical progression ,

have necessary laboratory analyses repeatedappropriate counseling and
support provided.. All information should be recorded in patients' medical
chartsand OPC log book.

6.1. Clinical monitoring

At each follow­up visit, patients should be assessed clinically, to monitor the
clinical course, to identify and manage the drug side effects or the occurrence
of new OIs
­ Monitor weight, temperature, pulse, blood pressure and activity
performance.
­ Monitor drug side effects related signs and symptoms.
­ Detect new or recurrent OIs; differentiate IRIS or treatment failure for
timely and appropriate management.
­ Reassess clinical stage.
­ Assess possibility of pregnancy for substituting ARV if indicated (not
using EFV in pregnant women in the 1st trimester of pregnancy)
Clinical signs of good response to ART:
− Patients gain weight, have good appetite, and are more active.
− Disappearance of OIs and HIV related conditions
6.2. Laboratory monitoring

Before During ARV treatment

Regular tests initiati
on of 4 weeks 6 12 Every
ART months month 6
s month
s

CD4 � � � �

CBC/Hb, ALT � � � �

CBC/Hb, if using AZT � � � � �

containing regimen

ALT, if using NVP � � � � �

containing regimen

 66

Creatinin, if using TDF � � � �

based regimen

Fasting blood lipid, and � once a year or when patients present

glucose if using PI with manifestations of lipodistrophy
containing or other
regimens

Viral load* (if available) � � �

Note:
During ART monitoring, if patients present with abnormal signs and symptoms,
the doctors can request other tests necessary to support diagnosis and
treatment.
6.3. Adherence monitoring
The adherence to treatment should be assessed at each follow­up visit.
− Assess the patients’ compliance by counting the number of tablets left, by
patients self­report, patients' note book, report of supporters (if available),
and by clinical course and laboratory analyses..
− Review with the patients drug taking schedule and management when
missing a dose.
If patients have not complied with therapy, find out the causes. The patients
need careful counseling on how to overcome the problems and barriers, and
timely support to achieve good adherence.

Guide for patients in case of missing an ARV dose:

Right after recognizing missing a dose, take immediately the missed dose.
Then calculate the time remained from this moment to the next regular dose
(in hours):
− If the time remained is more than 4 hours, take the following dose at the
scheduled time;
− If the time remained is less than 4 hours, DO NOT take the following
dose at the scheduled time, but wait until it reaches at least 4 hours to
take the next dose.
− If more than 2 doses were missed in a week, discuss with treating doctors..

 67

7. Immune Reconstitution Inflammatory Syndrome (IRIS)

7.1. Definition:
Immune reconstitution inflammatory syndrome (IRIS) is characterized by
unexpected deterioration in clinical status of HIV­infected patients after the
initiation of antiretroviral therapy, due to recovery of immune system.
The nature of IRIS is the overt inflammatory response of newly reconstituted
immune system to live microorganisms in the body or the antigens of these
agents.
Common manifestations of IRIS may include:
­ The occurrence of OIs which were not recognized before starting ART
(such as TB, MAC, Cryptococcus meningitis, etc.)
­ The excessive deterioration of OIs which have been treated before starting
ART.
­ The worsening of co­infections (hepatitis B and C) and autoimmune
diseases (psoriasis, dermatitis, etc.).
Timing: IRIS typically occurs within 2­12 weeks of initiation of ART, but can do
so at latter time.
7.2. Incidence and risk factors
IRIS occurs in about 10% of patients initiating ART. Risk factors for IRIS
include:
­ Low CD4 cell count before the initiation of ART (IRIS occurs in about 25%
of patients with CD4 count below 50 cells/mm3 at initiation of ART).
­ History of OIs before initiation of ART. The closer the time of ART initiation
to OI treatment, the higher risk of getting IRIS.
­ Use of potent ARV regimen (e.g. PI/r based regimen).
To prevent IRIS, patients should be screened and treated for OIs before
starting ART, particularly TB.
7.3. Manifestations of IRIS
Opportunistic infections and non­ infectious diseases associated with IRIS:
�
­ Mycobacterial diseases: TB (most common), MAC.
�
­ Fungal infections: Cryptococcus neoformans, Penicillium marneffei, PCP.
�
­ Viral diseases: CMV, Herpes simplex and herpes zoster, HBV, HCV,
�
progressive multifocal leukoencephalopathy

 68

­ Prozoal diseases: toxoplasmal encephalitis, leishmaniasis

­ Non infectious diseases: psoriasis, thyroiditis

7.4. Diagnosis of IRIS

IRIS should be considered in patients after initiation of ART who adhere
well to therapy but present with clinical deterioration, especially if patients have
been in advanced stage of immunodeficiency with low CD4 count or OIs
before starting ART.
AND it is necessary to:
o Exclude drug toxicity, new OIs
o Exclude treatment failure if patients have been on ART for more than
6 months.
7.5. Management of IRIS
­ Some IRIS may be mild and resolve without treatment, and no treatment is
required.
­ Continue ART if patients can tolerate the regimen.
­ Treat unmasking OIs according to causes; modify ARV regimen and doses
if there is an interaction between ARV and OI drugs (e.g. replace NVP with
EFV if patients are on rifampicine based anti­TB therapy and if EFV is
available). Resume the original regimen after completion of OI therapy.
­ Discontinue ART temporarily only if patients are severe and cannot tolerate
the regimen. Follow ART discontinuation procedure if applicable (stop NVP
or EFV first; continue with other NRTI drugs for 7 days and then stop).
Restart ARVs when inflammatory syndrome is improved and patients can
tolerate the drugs.
­ Consider corticosteroid therapy in moderate to severe cases of IRIS. Oral
or parenteral prednisolone or methyl­prednisolon can be given at 0.5­1,0
mg/kg/day until the patients’ condition improves, then taper over 1­2 weeks.
­ Provide other interventions if necessary, such as surgical drainage of lymph
node abscess, surgical relief of bowel or tracheal obstruction.

8. First­line treatment failure and second­line regimens

8.1. Treatment failure assessment:

 69

Only consider treatment failure if patients have been on 3­drug ART for at
least 6 months and are compliant with treatment. Clinical events that occur
during the first 6 months of ART usually include OI, IRIS, or drug toxicity.

Criteria for determining1st line treatment failure:

Table 15. Criteria for determining 1st line treatment failure:

Clinical Occurrence or recurrence of stage 4 diseases or

failure conditions after at least 6 months of therapy a, b

Immunological − CD4 count returns to or falls below pre­therapy

failure c baseline level or
− 50% decline from the on­treatment peak value since
the initiation of ART (if known); or
− CD4 count < 100 cells/mm3 after a year without any
increase.

Virological Plasma viral load > 5,000/ml

failured

Note:
a. �Some clinical stage 4 conditions (lymph node TB, uncomplicated TB
pleural disease, esophageal candidiasis, recurrent bacterial pneumonia)
are not considered indicators of treatment failure. Treat these OIs first,
and if response is good, continue with 1st line regimen.
b. �Some clinical stage 3 conditions (e.g. TB, severe bacterial infections)
can be considered indicatiors of treatment failure. TB occurring 6
months after ART is considered as treatment failure when it presents
with immunological or virological failure. If these investigations cannot
be done, consider treatment failure if patients have other clinical staging
3, 4 conditions or disseminated TB.
c. � Concomitant infections can cause transient CD4 cell decrease; treat
these infections first, perform CD4 count when patients are stable.
d. �Viral load is best indicator for determining treatment failure. Switch to
the regimen if viral load is > 5,000 copies/mml at two tests with at least 1
month interval.

8.2. Procedures when treatment failure suspected:

 70

­ Reassess patients’ adherence. If adherence is poor, provide enhanced

counseling and support; reassess treatment failure criteria after patients
adhere well to therapy.
­ Assess patients’ history of ART, if they ever used suboptimal regimen (e.g.
low­dosed, regimen with 2 drugs).
­ Check if there is any interaction between current ARV regimen and drugs
for OI treatment and prophylaxis or other concomitant drugs.
­ Check if there are any factors that influence drug absorption, such as
diarrhea, vomiting, drug side effects, etc.
­ Assess for OIs and other concomitant conditions, provide timely
management.
­ Exclude CD4 changes due to variation in performance of CD4 count
machines or testing CD4 by different machines.
­ If patients present with clinical and immunological failure, viral load testing
should be performed if possible before switching to second­ line regimen
­ Consultantation with ART experts should be conducted when diagnosing
treatment failure and switching to second­ line regimen considered

8.3. Guide for switching to second­line regimen

Decision to switch to 2nd line regimen is based on integrated consideration of
clinical, immunological and viral criteriaa (if available).

Table 16: Integrating clinical status, CD4 cell count and viral load to
guide switching

Treatment Clinical Stage 1 and 2 Clinical Clinical

Failure Stage 3 Stage 4
Criteria
Consider Switch to
CD4 failure Do not switch
switching to second­line
(Viral load Follow patient for second­line regimen.
testing not development of clinical regimen.
available) signs or symptoms.
Repeat CD4 cell count in
three months.

 71

 Switch to second­line Switch to Switch to

CD4 and
regimen. second­line second­line
virological
regimen. regimen.
failure

8.3.1 Choice of 2nd line regimen:

1st line regimen 2nd line regimen

d4T/AZT + 3TC + NVP or TDF + 3TC (+ AZT)

EFV
or ddI + ABC

TDF + 3TC + NVP/EFV ddI + ABC

LPV/r
or +
AZT + 3TC

AZT or d4T + 3TC + EFV or NVP + ddI

TDF or ABC

• Alternative PI for LPV/r is ATV/r heat stable tablets

• If patients have history of using multiple ARVs in the 1st line regimen, the
virus may be already resistant to 2nd line drugs. Do genotyping if possible
to guide choice of appropriate regimen.
Toxicity of ARVs of second ­line regimens and management

Drugs Side effects or toxicity Management

TDF Renal toxicity Give lower TDF dose when patients have
renal failure. Replace TDF by ABC.
Influence into bone growth
Avoid using TDF in pregnant women and
children.

 72

ddI Lactic acidosis Discontinue ART; provide supportive

treatment and laboratory monitoring
Pancreatitis Restart ART when patients are completely
stabilized; replace ddI by appropriate NRTI
Peripheral neuropathy,

Fat redistribution: loss of

subcutaneous fat (in the face, arms,
legs), and central fat accumulation
(in visceral, breast, abdomen, neck);
increase in blood lipids; alteration in
glucose metabolism
ABC Hypersensitivity: commonly occurs in Discontinue ABC and never give it again
the first 6 weeks of treatment; (re­challenge is associated with
manifestations: diffuse rash (may cardiovascular collapse and death). Give
presents without rash); fever, fatigue; symptomatic treatment
nausea, vomiting, diarrhea; difficult
breathing, cough, sore throat;
increase ALT, phosphatasa, LDH
LPV/r Hepatitis Assess severity of ALT increase (annex 7).
If grade 1, 2: continue with regimen and
monitor. If grade 3: change to other PI if
available. If grade 4: discontinue ART and
monitor; after patient improves, re­start
ART, change LPV/r to other PI
Lipodystrophy: fat accumulation Grade 1 or 2 increase in cholesterol and
(internal organs, breast, neck); triglyceride ­ apply diet, physical exercises
increase in blood triglyceride; and monitor. Grade 3 or 4 ­ use fibrate
disturbance in glucose metabolism drugs (fenofibrate 600mg 1­2 times/day);
(insulin­resistant diabetes mellitus treat hypecholesterolemia with statin drugs
and increased risk of cardiovascular (do not use simvastatin due to interaction
diseases, pancreatitis). with PI).

ATV/r Elevated indirect­ bilirubin, Usually asymptomatic or mild jaundice

without ALT elevation. Replace ATV by
other PI

Central fat accumulation (internal Management of side effect due to LPV/r

organs, breast, neck; increase in
cholesterol and triglyceride, insulin­
resistant diabetes mellitus and high
risk of cardiovascular diseases,
pancreatitis

 73

 1st degree atrio­ventricular block Use with caution in patients with

(prolonged PR on ECG) underlying conduction disturbances or on
concurrent use of drugs causing prolonged
PR

8.3.2. Dosage and administration of 2nd line regimen:

Before switching to 2nd line regimen, it is necessary to:
­ Counsel patients to reinforce the adherence to therapy; give the second
line regimen when the patients show ability to adhere to the regimen.
­ Treat clinical events (stage 3, 4 manifestations).
­ Counsel carefully on the new regimen.
Dosage and administration of 2nd line drugs:
­ Tenofovir (TDF): 300mg once a day p.o.
�
­ Abacavir (ABC): 300mg b.i.d orally, every 12 hours or 600mg once daily
�
­ Didanosin (ddI): for patients < 60kg – 250mg once a day p.o.; ≥ 60kg –
�
400mg once a day p.o.
­ Lopinavir/Ritonavir (LPV/r): 400mg/100mg b.i.d, every 12 hours; LPV/r
(capsule) should be taken on full stomach; for LPV/r tablets. : no diet
restriction.
­ Atazanavir/Ritonavir (ATV/r): 300mg/100mg once daily p.o.
­ Lamivudine (3TC) and Zidovudine (AZT): dosage and administration are
similar to that of 1st line regimen.
8.4. Monitoring patients who are on 2nd line regimen:
­ Ensure treatment adherence
­ Monitor the drug interactions when using LPV/r
­ Assess clinical and CD4 response similarly to that of 1st line regimen
9. Antiretroviral therapy for patients with specific conditions:

9. 1. ART for patients with TB/HIV co­infection

­ Patients with TB/HIV co­infection have higher risk of death than those with
HIV alone, and therefore need timely initiation of ART.
­ As TB/HIV co­infected patients often have to take multiple tablets,
treatment adherence, interaction between ARV and TB drugs (such as
rifampicin) and risk of hepatoxicity should be taken into account.

 74

9.1.1. Initiation of ART in HIV/TB co­infected patients:

9.1.1.1. Criteria for initiating ART in HIV/TB patients:
a. The patients are ART naïve and CD4 count available:
Table 18: Initiation of ART for TB patients with CD4 count available

CD4 Management

CD4 >350 cells/mm3 Start TB therapy first. Assessfor ART after

intensive phase or after completion of TB
treatment. If the patient is at clinical stage 4,
ART can be started after the patient tolerates
TB drugs (between 2 to 8 weeks of TB
treatment).

CD4 250­ 350 /mm3 Start TB therapy first.

Start ART after completion of intensive phase of
TB therapy.
If the patient is at clinical stage 4, ART can be
started after the patient tolerates TB drugs
(between 2 to 8 weeks of TB treatment).

CD4 < 250 /mm3 Start ART as soon as possible, after the patient
tolerates the TB drugs (between 2 and 8 weeks
of TB treatment).

b. The patients are ART naïve and CD4 count not available:
Table 19: Initiation of ART for TB patients without CD4 count

Clinical status Management

Pulmonary TB only (no other ­ Complete intensive phase of TB

clinical stage 3 or 4 conditions) therapy, then assess for ART.

Pulmonary TB with other clinical ­ Start TB therapy first.

stage 3 conditions
­ Start ART after completion of
intensive phase of TB therapy.

Pulmonary TB with other clinical ­ Start TB therapy first.

 75

stage 4 conditions ­ Start ART as soon as possible,

after the patient tolerates TB
Extra­pulmonary TB.
therapy (between 2 and 8 weeks).

9.1.1.2. Choice of 1st line ARV regimen for HIV/TB patients:

Table 20: 1st line regimens for HIV/TB patients starting ART

Patients on TB therapy with rifampicin and starting ART:

Preferred 1st line regimens: AZT/d4T + 3TC + EFV
Alternative regimens:
� If EFV is not available, or for women in the first trimester of pregnancy,
and CD4< 250 cells/mm3
AZT or d4T + 3TC + NVP
� For women in the first trimester of pregnancy, and CD4 > 250
cells/mm3
AZT + 3TC + NVP with closed monitoring for side effects; or
AZT + 3TC + ABC or
AZT + 3TC + LPV 400mg/RTV 400 mg
� For patients not tolerating NVP and EFV:
AZT + 3TC + TDF
Note: Avoid using this regimen for pregnant women, if possible.

Dose: The same as for HIV patients without TB, increase RTV dose from
100mg to 400 mg.

Patients on TB therapy without rifampicin: use the 1st line regimens as for
patients without TB

9.1.2. TB occuring in patients who are on ART:

TB occuring in patients while they are on ART can be IRIS (during first 6
months), new infection, or treatment failure.
9.1.2.1. TB occuring in patients while on ART

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­ Treat TB in accordance with national TB guidelines. Modify ARV regimen if

necessary.

Table 21: ART for TB patients on rifamicin regimen

Current ART regimen Preferred ART regimen for patients on TB

therapy with rifampicine

First­line ART Regimens

d4T or AZT + 3TC + EFV − Continue with EFV­based regimen

d4T or AZT + 3TC + NVP − Replace NVP with EFV

− If EFV not available, or the patients are
pregnant women, or patients cannot
tolerate EFV, continue NVP­containing
regimen at normal doses, but monitor
closely for clinical symptoms of hepatitis
and liver enzyme level every 2 weeks, or
− Change to AZT + 3TC + TDF regimen

2nd line regimens

2 NRTI + LPV/r Switch to or continue (if in use) 2nd line

regimen with LPV 400 mg/ RTV 400 mg

− If patients are too severe to continue the ART, discontinue the regimen
temporarily and give anti­TB drugs. When patients’ condition is stabilized,
resume the original ART regimen with consideration of drug interactions
(see Annex 5).
− When patients complete rifampicin therapy, consider resuming NVP; in this
case, restart with full dose of NVP 200mg, twice per day.

9.1.2.2. Choice of 2nd line ARV regimen for TB patients who have 1st line
regimen treatment failure:
− The 2nd line regimen for patients on TB therapy with rifampicin is similar to
that for patients without TB with the dose of ritonavir increased: LPV
400mg/RTV 400mg.
− Monitor the patients closely to detect liver toxicity.

 77

9.2. Antiretroviral therapy for HIV patients with viral hepatitis B and/or
hepatitis C co­infection:
­ The criteria for ART eligibility for patients co­infected with hepatitis B and
hepatitis C are the same as for other HIV­infected patients.
­ Pay special attention to drug interactions and hepatoxicity in choosing the
appropriate ARV regimen.
9.2.1. ART for HIV/HBV co­infection
9.2.1.1. Choice of ARV regimen for HIV/HBV co­infected patients:
Preferred first line regimens: AZT or d4T + 3TC + EFV
Alternative regimens: AZT or d4T + 3TC + NVP
Note:
− EFV is the preferred NNRTI for HIV/HBV co­infected patients, patients with
clinical hepatitis or increase in ALT.
− When EFV is not available, NVP can be used for patients with increased
ALT with closed monitoring.
− For patients taking NVP, when ALT increases to grade 3 or 4, NVP should
be replaced by EFV , TDF or LPV/r
9.2.1.2. Management of HBV hepatic flare when patients are on ART:
Hepatic flares may occur in patients with HIV/HBV co­infection in the first
several months of ART as part of IRIS, or as consequences of discontinuation
of ARV drugs which also have effect on HBV virus (e.g. 3TC, TDF).

− Manifestations: rapid increase in liver enzyme levels, with signs and

symptoms of hepatitis (such as fatigue, abdominal pain, and jaundice).
Sometimes it is very difficult to make differentiation with hepatoxicity due to
ARV drugs.
− If ALT increases to grade 3 and the clinical status of the patients is stable,
continue ART with less hepatotoxic drugs, such as EFV; monitor closely
ALT levels (every 2 weeks) and clinical symptoms;
− Monitor closely HIV/HBV coinfected patients if they have to stop ARV
drugs, including 3TC, TDF.
9.2.2. Antiretroviral therapy for HIV/HCV co­infected patients:
Choice of ARV drugs is similar to HIV­infected patients without hepatitis C, and
�
EFV is preferred NNRTI.
�
Notes on using ARV drugs in patients with HIV/HCV co­infection:
�

 78

 − ARVs have no activity against HCV.

− Treat hepatitis C with interferon and ribavirin (RBV), if possible. AZT
concentration is increased when used concomitantly with RBV; monitor
the AZT toxicity closely. Good response to hepatitis C treatment is
observed when patients’ CD4 count is more than 200 cells/mm3.
9.2.3. Antiretroviral therapy for patients with high ALT at baseline or unknown
HBV, HCV hepatitis status:
− Do ALT testing for all patients before starting ART as regulated.
− Screen for HBsAg and anti­HCV before starting ART or when ALT
increases, if feasible.
− When patients’ ALT increases with known or unknown HBV, HCV
status, EFV based regimen should be used.

9.3. Antiretroviral therapy for injecting drug users (IDUs)

9.3.1. Principles of Antiretroviral therapy in IDUs:
­ Criteria for initiating ART for IDUs are similar to other HIV­infected
patients.
­ Do not delay ART for patients with history of or current IDU.
­ Ensure the treatment readiness for patients and their treatment supporters,
including readiness to adhere to therapy; provide supportive counseling
during treatment.
­ Special attention should be paid to drug interaction between ARV and
opioid substitution therapy drugs (e.g methadone) and risk of hepatoxicity,
especially in IDUs with HBV/HCV co­infection.
9.3.2. Choice of ARVs for HIV infected IDUs.
Choice of 1st line regimen drugs is similar to that for other patients, and
includes:
Preferred first line regimens: AZT or d4T + 3TC + NVP
Alternative regimens: AZT or d4T + 3TC + EFV
Notes:
­ Screen for HBsAg and anti HCV prior to initiation of ART, if possible. If
patients have increased ALT and/or HBsAg (+) and anti­HCV (+): see
section on ART for patients with HIV/HCV/HBV co­infection.

 79

­ EFV/ NVP decrease the plasma levels of methadone in patients taking

methadone substitution therapy, which may precipitate symptoms of opiate
withdrawal. Consider increasing doses of methadone.
­ Choice of 2nd line regimens is similar to that for other patients; note that
LPV and RTV decrease the plasma levels of methadone, resulting in opioid
withdrawal syndrome in patients on methadone substitution therapy.
9.3.3. Treatment support:
� Support the patients to stabilize the life and support the adherence to
therapy through the help of families, peer groups, healthcare workers, and
social support services including vocational support, micro­credit and job
creation program.
• Apply DOT (direct observation therapy) approach if possible and if
necessary. This activity is easier to be carried out in social support centres.
• Introduce harm reduction intervention programs including outreach
services, condom supplies, clean needle and syringe provision, opioid
substitution therapy with methadone.
• Coordinate with drug rehabilitation centres and prisons to ensure
continuation of treatment for patients on ART being referred from
community to closed settings.

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VII. ANTIRETROVIRAL THERAPY IN PREGNANT WOMEN AND PREVENTION OF

MOTHER­TO­CHILD TRANSMISSION OF HIV (PMTCT)

Principles

­ HIV status of pregnant women need to be defined early for timely application
of measures to prevent the transmission of the virus to the babies, which
include ARV prophylaxis , substitution feeding for the infant and referral for
postpartum care and treatment services.
­ HIV­infected pregnant women need referral and consultation with HIV/AIDS
care facilities for assessment if they are eligible for ART or need ARV
prophylaxis for PMTCT.

­ Pregnant women are given priority in ART when eligible. The preparation
period for ART can be shorten to ensure timely and effective ARV
prophylaxis to prevent MTCT.
­ Use the most effective regimen for PMTCT. After delivery, the mother need
eassessment for clinical and immunology status for ART. If not yet eligible,
stop ARV; if eligible, use ART regimen as for other HIV infected adults.
1. ARV therapy for HIV­infected pregnant women

ART for pregnant women is long­term use of ARV to treat HIV infection for the
health of pregnant women themselves as well as to prevent transmission of
HIV to their babies.
1.1. Initiating ART in pregnant women
1.1.1. Criteria for ART initiation in pregnant women:
The criteria for initiating ART in HIV­infected pregnant women are similar to
that for non­pregnant HIV positive adults, as follows:

Criteria for initiation of ART in pregnant women:

­ Clinical stage 4: commence ART regardless of CD4 cell count

­ Clinical stage 3: commence ART when CD4 < 350 cells/mm3

­ Clinical stage 1, 2: commence ART when CD4 < 250

cells/mm3

If CD4 count is not available, ART should be given when pregnant

women are at clinical stage 3 or 4

1.1.2. ARV regimens for HIV­infected pregnant women

Preferred regimen:
 
81
 AZT + 3TC + NVP
�
� Use during pregnancy, intra­partum and postpartum. Dosage of ARVs
for pregnant women is similar to that for other HIV­infected adults.
� Monitor closely ALT level, especially in pregnant women with CD4 from
250 – 350 cells/mm3. ALT test should be done before starting ART,
every 2 weeks in the first month, , once per moth from the second to
fouth months and then once every 3 months thereafter. Change to
appropriate regimen if patient has hepatotoxicity ;

Alternative regimen:
­ When AZT cannot be used: Replace AZT with d4T or ABC

­ When NVP cannot be used because of hypersensitivity or toxicity, use one

of the following options in the priority order:

+ AZT + 3TC + EFV (if gestation age > 12 weeks); or

+ AZT + 3TC +LPV/r; or

+ AZT + 3TC + ABC

Note:

­ HIV­infected pregnant women with active TB and on TB treatment with

rifampicin should have drug interaction with NVP or toxicity of EFV in the
first trimester of pregnancy considered when selecting ARV regimen (see
the Section of ARV treatment for patients with TB/HIV).

­ After birth, the mother can continue the same regimen or change to the
preferred first line regimen.

1.2. Women who become pregnant while receiving ART

Women who become pregnant while receiving ART: continue original ARV
regimen, with the considerations:
­ Ifthe women are using EFV and gestation age is <12 weeks: replace EFV
with NVP (use 200mg twice a day without lesd­in dose) or appropriate
alternative regimens. Counsel on risk of HIV infection with children and
discuss the plan of keeping/not keeping fetus with pregnant women.
­ EFV based regimen can be continued during 2nd and 3rd trimesters of
pregnancy.

 
82

1.3. ARV prophylaxis regimen for children borne to mothers who have
been taking antiretroviral therapy

If the mothers have been on ART > 4 weeks:

AZT syrup 4mg/kg b.i.d x 7 days

If the mothers have been on ART < 4 weeks:

AZT syrup 4mg/kg b.i.d x 4 weeks

1.4. ART Regimen for post­partum women who had been provided single
dose of NVP for PMTCT:
­ If the woman meet treatment criteria within 6­12 months after delivery:

+ � Use standard 1st line regimen as for other HIV infected adults (see
Section on ART for adults)
+ � Use AZT + 3TC + TDF; or replace NVP by EFV or LPV/r to avoid drug
resistance
­ If the woman meet treatment criteria for ART after6­12 months after
delivery: use standard 1st line regimen as for other adults.

2. Antiretroviral prophylaxis for preventing mother­to­child transmission of HIV

Antiretroviral prophylaxis for PMTCT is short term use of antiretroviral drugs to

prevent the transmission of HIV from HIV­infected pregnant women to their
babies.
2.1. Who needs prophylaxis with ARV for PMTCT
­ HIV­infected pregnant women not eligible for antiretroviral therapy (those
with clinical stage 1­2 and CD4>250 cells/mm3, clinical stage 3 and
CD4>350 cells/mm3), or;

­ HIV­infected pregnant women eligible for ART, but cannot access ART
service or;

­ HIV­infected pregnant women not attending antenatal care services or

being diagnosed with HIV late during labor and delivery.

­ Infants born to HIV positive women

2.2. PMTCT ARV regimens for the mother and newborn

2.2.1. Preferred regimen: AZT + single dose of NVP:

 
83

This regimen is given to all HIV (+) pregnant women in antenatal care facilities
to prevent HIV transmission from mother to child.
Table 22: Use of AZT + single dose NVP regimen for PMTCT

Mother AZT 300mg b.i.d from week 28 (or as soon as possible

thereafter when women are diagnosed with HIV) until labour
Antepartum

Intrapartum At the beginning of labour:

NVP 200mg + AZT 600mg + 3TC 150mg
Then AZT 300mg + 3TC 150mg every 12 hours until
delivery

Postpartum AZT 300mg + 3TC 150mg every 12 hours for 7 days

Infants If the mothers have been on AZT > 4 weeks before birth
Single dose NVP 6mg, immediately after birth + AZT
4mg/kg b.i.d. x 7 days
If the mothers have been on AZT less than 4 weeks before
birth
Single dose NVP 6mg, immediately after birth + AZT
4mg/kg b.i.d. for 4 weeks

Note: Side effect of AZT is anemia, which is not commonly seen in pregnant
women with short duration of treatment. Monitor the clinical manifestation of
anemia and Hgb level closely, give treatment if needed.
2.2.2. ARV PMTCT regimens if pregnant women diagnosed with HIV during
labour:
ARV prophylaxis is indicated when HIV infected pregnant women have not
been monitored during pregnancy, or pregnant women diagnosed with HIV
lately during labour and at delivery.
Table 23. ARV regimens for PMTCT if the mother appear at labour

Mother At the beginning of labour:

NVP 200mg + AZT 600mg + 3TC 150mg
During labour
Then AZT 300mg + 3TC 150mg every 12 hours until
delivery

 
84

Postpartum AZT 300mg + 3TC 150mg every 12 hours for 7 days

Infants Single dose NVP 6mg, immediately after birth + AZT

4mg/kg b.i.d. for 4 weeks

Note:
a. �Pregnant women with a positive HIV screening test at labor should be
counseled and provided with an appropriate PMTCT ARV regimen;
confirmation of infection can be performed later. If the HIV status is not
confirmed, stop ARV and other PMTCT intervention.
b. �Do not give ARV prophylaxis to mothers if delivery is expected to happen
within 1 hour; the infants should be provided with ARV as above.
c. � If AZT is unavailable, give mother single dose NVP during labour and the
infants single dose NVP after birth.
3. Other interventions and referral for the mothers and their infants to care and
treatment services after birth

3.1. Interventions for the mothers:

a. Before delivery:
­ Give adequate counseling before and after HIV testing
­ Counsel on nutrition during pregnancy and on feeding of the baby after
birth
�
­ Counsel on psychosocial support
�
­ Train for ARV treatment readiness and ARV adherence
�
b. During delivery:
­ Follow strict measures of aseptics in obstetrics
­ Avoid procedures such as amniocentesis, cesarean section, placing
electrodes on the fetus’ head, etc.
­ Wash the newborn right after birth.
c. After delivery:
­ Dispense adequate dose of ARV the mother if the mother and infant
can be discharged early
­ Refer the mother to adult HIV care and treatment facilities for longterm
care
3.2. Interventions for the infants:

 
85

a. Dispense adequate dose of ARV to the infant and instructing the mother or
care­giver about ART adherence. Schedul follow­up visits for dispensing drugs
and further counseling if necessary
b. Counsel on Feeding interventions:
­ Counsel the mothers about the benefit of breastfeeding and the risk of
HIV transmission with breast feeding. Use full replacement feeding for
infants if available (source of milk, clean water, food hygiene).
­ If breast feeding, counsel adequately on:
o Feeding position, how to hold the nipples and how to manage
when the nipples fissure and breast abscess occurs.
o Weaning as soon as possible to avoid risk of mother to child HIV
transmission.
c. Refer the infant to:
­ HIV care and treatment facilities for children, for longterm care and
monitoring when the infant is 4­6 weeks of age
­ If the infant is orphaned, encourage the family to continue care or refer
the child to an orphanage.
VIII. POST­EXPOSURE PROPHYLAXIS

1. Post­occupational exposure prophylaxis

Occupational exposure to HIV is considered when direct contact with HIV

contaminated blood or body fluids occurs, which can result in transmission of
HIV.
1.1. Modes of exposure:
­ Needle stick injuries while performing injection, taking blood sample, body
fluid tapping, etc

­ Injuries from surgical scalpels and other sharp instruments that have
patient's blood or body fluids on.

­ Percutaneous injuries from broken tubes which contain patient's blood or

body fluids.

­ Pre­existing skin lesions (eczema, burn, old ulcers, and inflammation of

skin) or mucous membrane (of the eyes, nose and throat) contaminated
with patient's blood or body fluids.

­ Others: contaminated needle stick injuries when chasing criminals, etc…

1.2. Protocol for post­exposure management

 
86

Post­exposure management includes the following steps:

1. �Treatment of exposure site
2. �Report the exposure to the manager and complete the report form (fill
in all the information as required in the Exposure record)
3. �Assess the risk of exposure according to the severity of injury and
contact.
4. �Determine the HIV status of the source of exposure
5. �Determine the HIV status of the exposed person.
6. �Counsel the exposed person.
7. �Provide ARV prophylaxis for the exposed person

a. Treat the exposure site:

­ Bleeding wound of the skin:

+ Flush the wound with tap water

+ Let the wound bleed for a short time, do not squeeze
+ Clean the wound thoroughly with soap and water
­ Eye exposure: Wash the eyes with distilled water or NaCl 0.9% solution
continuously for 5 minutes.

­ Mouth and nose exposure:

+ Rinse the nose with distilled water or NaCl 0.9 % solution.

+ Gargle with NaCl 0.9 % solution for several times.
b. Report to the manager and complete the report form:
Indicate the date, time and the context of exposure, describe the wound
and assess the level of risk. Get the signatures of the witnesses and the
supervisor.
c. Assess the risk of exposure:
­ Risk presents with:

+ Bleeding percutaneous wounds caused by containing blood needles:

the risk is higher in case of deep wounds caused by large­bore
needle containing a lot of blood compared with that of shallow
wounds from fine needles with less blood.
+ Deep percutaneous wounds caused by scalpels or broken tubes
containing patient's blood and body fluids.
+ Existing lesions, ulcers or scratches on the skin or mucus membranes
exposed to patient's blood and body fluids (even when the status of
ulcers is unclear): the risk is higher with large ulcers or scratches.
­ No risk: normal skin exposed to patient's blood or body fluids.
 
87

d. Determine the HIV status of the source of exposure

­ If the source patient is HIV (+): get information on the use of and response
to ARV treatment

­ If the HIV status of the source is unknown: provide counseling and perform
HIV test

­ In some cases it is impossible to identify the HIV status of the source (being
exposed while on duty, the subject ran away).

e. Determine the HIV status of the exposed person.

­ Provide pre­test and post­test counseling as regulated

­ If the exposed person has positive test result right after the exposure
incident: HIV infection occurred before, not due to the exposure incident

­ If HIV (­): HIV test is required after 3 months and 6 months.

g. Counsel the exposed person on:

­ Risk of infection with HIV, HBV, HCV

­ Information and services of the prophylaxis, its benefits and risks.

­ Side effects of ARV and signs of primary HIV infection: fever, rash, nausea
or vomiting, anemia, lymphadenopathy, etc...

­ Prevention of HIV transmission to others: exposed person may transmit

HIV to others even if the test is negative (the window period) and they,
therefore should practice all prevention measures

­ Adherence to treatment and psychological support

h. ARV prophylaxis for the exposed person

Indications: Provide ARV treatment as soon as possible, best within 2 – 6
hours after and before 72 hours after the exposure to all exposure cases with
risk. At the same time, assess the HIV status of the source of exposure and
the exposed person.
­ If the source of exposure is HIV (+): continue the treatment.

­ If the source of exposure is HIV (­): it is possible to discontinue the treatment. If

the source is suspected as having risk factor and is in the period window, the
treatment should be continued..

­ If the exposed person is HIV (+): do not provide prophylaxis, refer for follow­
up and provide treatment as a normal HIV positive case.

­ If the exposed person is HIV (­): continue the treatment.

 
88

­ Exposure with no risk: no treatment is needed

­ If the HIV status of the source of exposure cannot be determined: treat as a

case of exposure to the HIV (+) source.

Table 24: Treatment of post­exposure prophylaxis with ARV

Medications Indications

2 drug regimen (basic AZT + 3TC or d4T + 3TC All exposures with risk
regimen)

3 drug treatment AZT + 3TC or d4T + 3TC In case the source of

regimen exposure is known with
plus: LPV/r
or suspected of ARV
resistance

Duration of treatment 4 weeks

i. Follow­up
­ Monitor the side effects of ARV:

­ Inform the person on post­exposure prophylaxis about the possible side effects,
not to stop taking the medications if the side effects are minor, and visit the
treatment doctor as soon as severe side effect(s) occur(s).

­ Do CBC and ALT tests on the start of the treatment and after 4 weeks.

­ Do HIV test after 3 and 6 months.

­ Provide psychological support if needed

2. Non­Occupational Post­Exposure Prophylaxis:

2.1. Definition:
Non­Occupational Exposure is the exposure to blood, body fluid which
happens outside of the occupational settings and can result in transmission of
HIV.
2.2. Non­Occupational Exposure situations:

 
89

­ Sexual exposure: Having sex without using condom or the condom slips or
breaks down, sexual assaults
­ Sharing syringe and needle with injecting drug user (single time);
­ Injuries from discarded needles that have visible blood stain on them
­ Human bites
2.3. Cases not considered for HIV prophylaxis:
­ Post­exposure prophylaxis should not be prescribed for people who repeatedly
expose to HIV such as having sex with HIV infected persons, or being sex
workers but rarely use condom, injecting drug users that frequently shares
syringes and needles.
2.4. �Factors requiring assessment for persons who may be exposed to
HIV in the non­occupational settings.
­ HIV status.
�
­ Situation, frequency and time of exposure. Try to assess the HIV status of the
�
source.
­ HIV pre­test counseling.
­ Perform HIV and pregnancy testing if needed
2.5. Assessment of the HIV status of the source

If the HIV status of the source is unknown, try to do HIV test. It is possible to
start the prophylaxis, and then stop if the source is confirmed as HIV negative.

When the source comes from the population groups with known high HIV
prevalence (such as MSM, IDUs, or sex workers), or the person has been
sexually assaulted and the HIV status of the source is difficult or impossible to
be identified, it is necessary to prescribe prophylaxis after assessing the risks
and providing counseling to the exposed person.

2.6. Post­exposure prophylaxis with antiretrovirals:

The procedure for ARV prophylaxis for the non­occupational exposure is

similar to that one after occupational exposure; it should be initiated as soon
as possible, within 72 hours after the exposure and continued for 28 days.
Two­drug ARV regimen should be used.

If the source of exposure has history of taking ARV at presence or in the past,
or is known as failing first line regimens, it is recommended to prescribe 3 drug
regimens.

Provide counseling on the side effects and treatment adherence prior to

prophylaxis.

2.7. Monitoring and support counseling

 
90

­ Explain about the plan of monitoring and testing after 1, 3, and 6 months, counsel
on adherence to treatment during the ARV prophylaxis.
­ Counsel on not giving blood, practicing safe sex and safe injection, and non­
breastfeed until the HIV status is confirmed or risk is eliminated.
­ Counsel on Hepatitis B vaccination if the person is Hepatitis B free, has not been
vaccinated or does not have antibody to HBV.
­ Counsel on avoiding further exposure to HIV

 
91

 PART B ­ DIAGNOSIS, TREATMENT AND CARE FOR

�
CHILDREN LIVING WITH HIV/AIDS
�

I. DIAGNOSIS, CLINICAL AND IMMUNOLOGICAL STAGING OF HIV INFECTION IN

CHILDREN

1. Diagnosis of HIV infection in children

1.1. Diagnosis of HIV infection in infants less than 18 months of age

HIV infection in infants less than 18 month of age, including HIV exposed
children (children born to HIV infected mother) and HIV suspected cases is
diagnosed on the basis of Polymerase Chain Reaction ( PCR for DNA or RNA
of virus.
Perform diagnosis followed the Ministry of Health guidelines on diagnosis of
HIV infection in infants under 18 months of age
1.1.1. Diagnosis of HIV infection in HIV­exposed infants under 9 months of age
Perform the virological test when the infant is 4­6 week of age, or as soon as
possible thereafter .
If the first PCR test is positive, 2nd PCR should be performed to confirm
diagnosis of HIV infection, along with clinical assessment for preparation of
ARV treatment
If the first PCR test is negative, or 2nd confirmatory test is negative, continue to
monitor the child and perform HIV antibody test at age 18 months to
confirm/rule out HIV status
If the first PCR test is negative and the infant is breastfed (or stop
breastfeeding less than 6 weeks prior to test), PCR test should be perform
when infant stop breastfeeding completely for more than 6 weeks.
During follow up, if infants have any sign or symptom suggestive of HIV
infection, HIV antibody test should be performed. In case antibody test is
positive, PCR test should be performed immediately.
1.1.2. Diagnosis of HIV infection in HIV­exposed infants from 9 to 18 months of
age
Perform HIV antibody test first. If the test is positive, PCR should be followed
as for infants under 9 months of age to confirmthe diagnosis.
1.2.3. Diagnosis of HIV infection in children under 18 months of age with
unclear exposure but having HIV suspected signs:
Follow the guideline for HIV­exposed infants from 9 to 18 months of age

 
92

1.2. Presumptive Diagnosis of severe HIV infection (stage IV) in infants less
than 18 months of age
Presumptive diagnosis of severe HIV infection is applied when the virological
testing is not available, and the infant has:
­ PositiveHIV antibody test, AND
­ One of the clinical stage 4 diseases or conditions, such as PCP,
cryptococcal meningitis, Toxoplasma encephalitis, unexplained severe
wasting, extra­pulmonary tuberculosis (excluding axillary lymph node TB as
complication of BCG), esophageal candidiasis,
OR
­ The infant has at least 2 out of the 3 signs:
1. Oral thrush (in infants older than 1 month of age)

2. Severe bacterial pneumonia

3. Severe sepsis.

Other indicators suggestive of severe HIV/AIDS, such as:

o The mother died from an HIV­related disease, or
o The mother is at advanced HIV/AIDS, or
o CD4 < 20%
Perform HIV diagnosis by virological testing as soon as possible.
1.3. Diagnosis of HIV infection in children ≥18 months of age
HIV infection in children older than 18 months is diagnosed by the serological
testing for HIV antibody. HIV infection is diagnosed if the serum sample is
reactive in all three anti­HIV antibody tests, which rely on different antigens or of
different operating characteristics

Note: Only laboratories designated by MoH are authorized to inform the HIV
positive test results.
2. HIV infection staging

A child with confirmed diagnosis of HIV infection needs to be assessed

for the clinical stage at each follow­up visit and the immunological stage every
6 months (infants with presumptive diagnosis of severe HIVinfection should
also have immunological test performed) .
2.1. Clinical staging:

 
93

 An HIV infected child is classified into 1 of 4 clinical stages, depending

on the symptoms and the most severe HIV­associated diseases presented.
Table 1: Clinical staging of HIV/AIDS for children with confirmed HIV
infection

Clinical stage 1: Asymptomatic

Asymptomatic
Persistent generalized lymphadenopathy

Clinical stage 2: Mild symptoms

Unexplained persistent hepatosplenomegaly

Papular pruritic eruptions
Fungal nail infections
Angular cheilitis
Lineal gingival erythema
Extensive wart virus infection
Extensive molluscum contagiosum
Recurrent oral ulcerations
Unexplained persistent parotid enlargement1
Herpes zoster (Zona)
Recurrent or chronic upper respiratory tract infections (otitis media,
otorrhoea, sinusitis, tonsillitis)

Clinical stage 3: Advance symptoms

Unexplained moderate malnutrition or wasting not adequately responding

to standard therapy
Unexplained persistent diarrhea (over 14 days)1
Unexplained persistent fever1 (above 37.5ºC constant or intermittent for
longer than 1 month)
Persistent oral candidiasis (after the first 6–8 weeks of life)

1
Unexplained refers to where the condition is not explained by other causes

 
94
 Oral hairy leukoplakia
Acute necrotizing ulcerative gingivitis
Lymph node TB
Pulmonary TB
Severe recurrent bacterial pneumonia
Symptomatic lymphoid interstitial pneumonitis
Chronic HIV­associated lung disease including bronchiectasis.
Unexplained anemia (<80 g/L), granulocytopenia (<0.5 x 109cells/L) or
chronic thrombocytopenia (<50 x 109 cells/L)1

Clinical stage 4: Severe symptoms

Unexplained severe wasting, stunning or severe malnutrition not

responding to standard therapy.
Pneumocystis jiroveci pneumonia (or PCP­ Pneumocystis Carinii
Pneumonia)
Recurrent severe bacterial infection (such as empyema, pyomyositis, bone
�
or joint infection, excluding pneumonia).
�
Chronic herpes simplex infection (orolabial or cutaneous herpes of more
�
than one month's duration or visceral herpes at any site)
�
Esophageal candidiasis (or candidiasis of trachea, bronchi or lungs)
�
Extra pulmonary tuberculosis
�
Kaposi’s Sarcoma
�
Cytomegalovirus infection: retinitis or CMV infection affecting other organs,
�
with onset at age > 1 month.
�
Central nervous system toxoplasmosis (after one month of life).
�
Extra pulmonary cryptococcosis (including meningitis)
�
HIV encephalopathy
�
Disseminated mycosis (endemic fungi such as penicillium, histoplasma)
�
Disseminated non­tuberculous mycobacterial infections.
�
Chronic cryptosporidiosis (with diarrhea)
�
Chronic isosporiasis
�
Cerebral or B cell non­ Hodgkin lymphoma
�

 
95

 Progressive multifocal leukoencephalopathy

Symptomatic HIV­associated nephropathy or HIV­associated
cardiomyopathy.

2.2. Immunological staging

The immune status of the HIV infected children is assessed by the
absolute number or percentage (%) of CD4 cells (percentage is applied for the
children under 5 years of age)

 
96

Table 2: HIV/AIDS immunological staging for children with confirmed HIV

�
infection
�

HIV­ Percentage of CD4 (or the absolute number of CD4/mm3)

associated
immuno­ > 5 years
<11 months 12–35 months 36 –59 months
deficiency (cells/mm3)

Not >35 % >30 % >25 % > 500

significant cells/mm3

Mild 30­35 % 25­30 % 20­25 % 350 – 499

cells/mm3

Advanced 25­29 % 20­24 % 15­19 % 200 – 349

cells/mm3

Severe <25 % <20 % <15 % <15%

<1500 <750 cells/mm3 <350 < 200
cells/mm3 cells/mm3 cells/mm3

If the CD4 count is not available, it is possible to assess the severity

of the immunodeficiency based on the total lymphocyte count (TLC) for the
children with clinical stage 2 or higher, but is not applied for monitoring the
response to ART.

Table 3: Diagnosis of severe immunodeficiency by total lymphocyte

count

Age­related total lymphocyte count cells/mm3

HIV­associated
severe
<11 12­ 35 36­ 59 ≥5
immunodeficiency
months months months years

Total lymphocyte <4,000 <3,000 <2,500 <2,000

count

CD4 count <1,500 <750 <350 <200

 
97

3. Diagnosis criteria of advanced HIV infection (including AIDS)

�

­ Any clinical stage 3 or 4 disease (confirmed or clinical diagnosis).

and/or
­ CD4 count (or total lymphocyte count if the CD4 count not available) below
the age­related thresold of advanced and severe immunodeficiency.
AIDS in a child with confirmed HIV infection is defined as clinical diagnosis
(presumptive or definitive ) of any stage 4 condition or the CD4 count below the
age­related level of severe immunodeficiency.

II. CLINICAL MANAGEMENT OF HIV EXPOSED INFANTS AND CHILDREN WITH

CONFIRMED HIV INFECTION

1. Initial assessment:

1.1. Clinical and laboratory assessment

1.1.1. Taking present history and previous medical history:

− HIV history of the parents and measures to prevent mother­to­child
transmission
− History of ARV use of mother and infant (reasons for use, duration,
specific regimen, treatment adherence)
− If the infant is diagnosed with HIV infection, ask for place of test, testing
time and method used
− History of prophylaxis with co­trimoxazole and immunization
− History of opportunistic infections and history of TB in the family
− History of drug allergy to antibiotics such as cotrimoxazole and ARVs, etc.
− History of feeding (breastfeeding or use of formula, nutritional issues);
physical and mental development.
− Recently occurred signs and symptoms
1.2.2. General and physical examination:
− Assess general condition, physical development (age­related height,
weight, head circumference, motion), mental development and
awareness.
− Overall vital signs, skin and mucocutaneous lesions

 
98

 − Assessthe status of respiratory, circulatory, neurologic organs and

….visual acuity (ear­nose­throat conditions), etc…
1.1.3. Laboratory:
− For infants under 18 months born to mother with HIV infection and infants
with HIV suspected but unconfirmed HIV status:
• Perform HIV testing in accordance with the age of children and as
soon as possible (HIV virological and serological testing)
• Provide pre­test counseling: benefits of HIV testing, procedures and
timing of HIV testing. If infant is breastfed, provide appropriate
counseling on HIV testing and its results during breastfeeding.
• Take the specimen and send to the laboratory for testing as
regulated
• Provide counseling when the test result comes back, and manage
per protocol.
− For infants with confirmed HIV diagnosis or infants with presumptive
clinical diagnosis of severe HIV/AIDS, the following test should be
performed:
• Complete blood count, total lymphocyte count, liver enzymes (ALT).
• TB screening (such as chest X ray, ESR, Mantoux test, sputum
AFB, etc.), or other necessary investigations for diagnosis of other
OIs
• CD4 count (if available).
− If infants present with opportunistic infections or other diseases,
appropriate test should be indicated.
1.1.4. Diagnosis of OIs and clinical staging:
− Diagnosis of active tuberculosis: (see Section V “Diagnosis and treatment
of common OIs in children with HIV infection”).
− Diagnosis of other OIs: see Section IV (Approach to common clinical
syndromes in children) and Section V (Diagnosis and Treatment of
common opportunistic infections in children).
− Clinical staging (see Section I, Section 2.1).
1.2. Management:
− Instruct replacement feeding with formula, if available or breastfeeding
and other nutritional cares according to age­related needs. For breastfed
infants with positive virological test, instruct the mother to continue
breastfeeding.
− Provide prophylaxis with co­trimoxazole and immunization as indicated.

 
99

 − Provide treatment for opportunistic infections, for symptoms and other

conditions as well as management of drug side effects (if any).
− Consider indication of ARV treatment if the infants are eligible. If infants
have OIs, treat those first. Start ART when condition stabilizes. If infants
have first PCR positive, preparation for ART should be done. For infants
with severe HIV/AIDS, provide ART without waiting for PCR test results.
− If the children are on ART, assess the regimen in use, and if the regimen
is not proper, seek for consultation.
− Admit to hospital the cases with severe OIs or serious side effects
− Seek for consultation from and refer patients to relevant specialized
facilities (dermatology & venereology, TB, etc.) or refer to higher levels if
beyond treatment capacity of the facility.
1.3. Counseling and support:

Counseling should be provided to the infants’ family on following issues:

− Evolution of HIV infection, importance of long­term care and treatment,
needs of following­up and HIV confirmative testing for the infants.
− Determine who are the main and supportive care givers for the infants.
− Immunization and prophylaxis for OIs.
− Nutrition issues, including benefits of breast milk and risks of HIV
transmission through breast milk, age­related feeding, avoid mixing of
breastfeeding and formula feeding, and weaning practices when infants
reach 6 months of age to avoid HIV transmission.
− Personal and food hygiene.
�
− School care, confidentiality and disclosure of HIV infection status of the
�
infants, preventive measures for HIV transmission, safe behavior practice.
− Psycho­social issues and treatment adherence
− Referal of the infants and their family to HIV care and treatment services.
− Supportive solutions for orphaned and abandoned infants
1.4. Follow­up plan and other necessary supports

− Schedule follow­up visit for each patient: every 1­3 months depending on
health status of the infant, ability to adhere to CTX prophylaxis, ability of
care givers to take care the infants, and on clinical and immunological
staging of the infants.
− For infants missing appointments, find out the reasons and establish
supportive measures such as further counseling, reminding calls, peer
supports, home visits, etc.

 
100

 − Schedule visits whenever abnormalities occur.

�
− Dispense drugs as prescribed.
�
− Coordinate the supports from family and community with available
�
services.
2. Follow­up visit:

HIV infected or exposed children should visit the clinic on regular basis or
whenever abnormalities occur. The following should be considered in addition to
the above­mentioned requirements:
2.1. Clinical examination and laboratory testing:
− Taking history: symptoms newly occurred since the last visit, such as
�
fever, weight loss, cough, diarrhea, eruption, etc.; psycho­social issues,
�
treatment adherence.
�
− Clinical examination: assess overall physical and mental development,
�
general and regional examination to detect opportunistic infections and
�
other conditions, side effects of prophylactic and therapeutic medications.
�
Re­assess clinical staging.
�
− Perform routine tests for infants with confirmed HIV infection (including
�
infants with severe HIV/AIDS), : CD4 cell count every 6 month; diagnostic
�
tests for OIs and tests for drug side effects as well as treatment failure as
�
needed. Regular assessment of treatment outcome in infants on ART
�
should be done as indicated.
�
2.2. Management:
Management will be provided depending on clinical condition and test
results of the children
− Treat OIs and manage drug side effects if any.
− Give ART treatment if the children are eligible.
− Provide nutritional, psycho­social counseling and support for treatment
adherence.
− Refer to other relevant services or consult with specialists when needed.
III. PROPHYLAXIS FOR OPPORTUNISTIC INFECTIONS, IMMUNIZATION SCHEDULE

1. Prophylaxis with co­trimoxazole (CTX)

a. Objective

Co­trimoxazole prophylaxis is effective to prevent PCP, Toxoplasma

encephalitis as well as diarrhea and respiratory tract infection due to some
kinds of bacteria.

b. �Indications of primary prophylaxis

 
101

 Table 4: Indications of prophylaxis with co­trimoxazole for HIV exposed

�
and HIV­ infected children
�

HIV exposed children HIV confirmatively infected children

< 1 year 1­5 years ≥ 5 years

If CD4 is available:
Clinical stage 3, 4
• CTX prophylaxis is
regardless of CD4
universally
indicated, starting • Clinical stages 2, 3 count.
at 4–6 weeks after and 4 regardless
Clinical stage 1, 2
birth and continued • Prophylaxis of CD4 count
with CD4 < 200
until exclusion of is indicated
Or cells/mm3
HIV infection for all
infected • CD4 < 25%
• If children are children regardless of
diagnosed with If CD4 is not
clinical stage
HIV, see next available:
columns
Clinical stage 2, 3,
4

c. Dosage of prophylactic CTX:

Cotrimoxazole consists of trimethoprim (TMP) and sulfamethoxazole (SMX).
Prophylaxis dose is 5 mg TMP/kg/day, once a day orally. Dosage can be
calculated as in following table:
Table 5: Dose of co­trimoxazole prophylaxis for HIV exposed and
infected children
Syrup (ml)
Body weight or body surface Tablet
area of the children (8 mg TMP/40 mg
(80 mg TMP/400 mg SMX)
SMX/1ml)
3.5 ­ 4.9 kg (0.21­ 0.28 m2) 2.5 ml

5.0 ­ 6.5 kg (0.28­ 0.33 m2) 4

6.6 ­ 8.0 kg (0.34­ 0.40 m2) 5 1/2

8.1 ­ 10. kg (0.41­ 0.47 m2) 6 1/2

10.1 ­11.9 kg (0.48­ 0.54 m2) 7 1/2

 
102

 12.0 ­ 14.9 kg (0.55­ 0.64 m2) 8 1

15.0 ­ 16.9 kg (0.65­ 0.71 m2) 10 1

17.0 ­ 19.9 kg (0.71­ 0.83 m2) 11 1

20.0 ­ 24.9 kg (0.83­ 0.98 m2) 1,5

25 ­ 29.9 kg (0.99­ 1.15 m2) 2

30.0 ­ 35.0 kg (> 1.15 m2) 2

d. Alternative drugs: Dapson 2mg/kg/day taken everyday or 4mg/kg/time, once

a week for the children with allergy to CTX. Dapson is less effective than Co­
trimoxazole in preventing PCP and has no effect on preventing toxoplasma.
e. When to stop CTX prophylaxis: When children on ART with CD4 higher
than 25% for children 1­5 years old and CD4 > 200 cells/mm3 for children
older than 5 years old, for 6 month continuosly.
g. Re­start CTX prophylaxis: when CD4 reduced and reaching the criteria for
prophylaxis according to age of infants.
h.Contraindication: Hypersensitivity to sulphonamides including CTX,
sulphadoxine­ pyrimethamine).
i. Side effects of CTX:
Nausea, vomiting and rash can occur during first 1­ 2 weeks after initiation of
prophylaxis; severe adverse reactions such as anemia, granulocytopenia, rash
and hepatotoxicity can also be seen.
Counsel the care givers and the children on side affects for self monitoring and
to seek consultation when suspected signs of severe adverse events occur.
Do complete blood count, liver enzymes measuring when anemia or
hepatotoxicity is suspected.
Rash due to CTX and how to manage
Table 6: Grading of rash due to CTX and management

Grade Clinical description Management

� Continue CTX prophylaxis with careful

Grade I Erythema
observation and follow up.
(Mild)
� Provide symptomatic treatment and
anti histamines.

 
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 � Continue CTX prophylaxis with careful

Grade II Diffuse maculopapular
observation and follow up.
rash, dry desquamation
(Moderate)
� Provide symptomatic treatment and
anti histamines.

Grade III Bulla, mucosal ulceration � Hospitalization with supportive

(Severe) treatment
� CTX should be permanently
Grade IV Exfoliative dermatitis,
discontinued
Stevens­Johnson
(Very
syndrome or erythema
severe)
multiforme, moist
desquamation

2. Immunization
�

HIV infected children, HIV infected

Exposed
Vaccines clinical stages 1, 2 children, clinical
infants
and 3 stage 4

Vaccines under the National Expanded Program on Immunization (EPI)

BCG1 As scheduled Do not give Do not give

Diphtheria­Pertussis­ As scheduled As scheduled As scheduled

Tetanus

Poliomyelitis, orally As scheduled As scheduled Only use injectable

vaccine, if available

Hepatitis B As scheduled As scheduled As scheduled

Measles As scheduled As scheduled Do not give

Japanese As scheduled As scheduled As scheduled

Encephalitis

Optional Vaccine
Haemophilus As scheduled As scheduled As scheduled
influenzae B
Varicella As scheduled As scheduled Do not give

Mumps As scheduled As scheduled Do not give

Rubella As scheduled As scheduled Do not give

 
104

Note:
­ Give BCG to all HIV­exposed children. Postpone vaccination until HIV
infection is excluded in following situations :
• High risk of HIV infection: The mother and the infant not receiving
PMTCT or
• The infant presents with signs or symptoms suggestive of HIV
infection. Or
• Low birth weight (under 2500 g) and pre­termed children.
­ BCG­associated disease can occur after BCG vaccination, presents with
swollen left axillary or left supraclavicular lymphnode, enlarged liver and
spleen, and cachexia. Consultation with TB specialists is needed for
assessment and treatment.

 
105

 IV. APPROACH TO COMMON CLINICAL SYNDROMES IN CHILDREN

WITH HIV/AIDS
1. Prolonged fever

Prolonged fever (a, b)

Give antipyretics, rehydration, good
nutrition
­ Take history (c) Examine
physically (d)

Suggestive causes of fever (e): Routine and cause­guiding

­ Respiratory findings: TB, PCP, bacterial investigations (e):
pneumonia ­ CBC, CD4 (if available)
­ Neurologic findings: Bacterial, TB, cryptococcal ­ Respiratory findings: CXR,
meningitis, Toxoplasma encephalitis, malaria sputum for AFB
­ Skin lesions: Penicilliosis, Cryptococcosis
­ Neurologic findings: PL
­ Lymphadenopathy: TB, MAC, fungal septicemia
­ Septicemia, penicilliosis: blood
­ Diarrhea: Salmonellosis, TB enteritis, MAC
­ Anemia: TB, MAC, fungal septicemia
� culture
­ History with medication: allergy
� ­ Lymphadenopathy: aspiration
­ Etc.... ­ Abdomen ultrasound, etc...

Empirical treatment (e):

­ Septicemia: appropriate antimicrobials Diagnosis confirmed by
­ Penicilliosis: itraconazole investigations, and/or

­ PCP: co­trimoxazole The child responds to empirical

­ TB: Anti­TB drugs therapy
­ Bacterial or cryptococcal meningitis: proper
antimicrobials
­ Toxoplasma encephalitis: co­trimoxazole
­ Etc... ­ Continue and complete
treatment.

­ Maintenance treatment if
Diagnosis not confirmed by indicated
investigations, the child does not
respond to empirical treatment

­ Re­evaluate clinically, consider other

causes, especially TB, MAC or fever due to
HIV itself
­ Do corresponding lab tests and
investigations; consider lymphnode biopsy,
bone marrow analysis and biopsy...
­ Treat presumptively for TB; MAC
­ Consider ARV treatment
 
106

Instructions:

(a) Definition: prolonged fever is defined as a fever over 3705 lasting for more
than 14 days.
(b) Common causes of prolonged fever
­ Common causes in HIV infection with severe immunodefficiency:
o TB, MAC, candidiasis, penicilliosis, cryptococcal meningitis and
fungal septicemia, systemic salmonellosis and septicemia due to
other bacteria, CMV diseases, etc...
o HIV related neoplasms: lymphoma,
o Fever due to HIV itself, malaria
­ Drug reaction: hypersensitivity to CTX or ARVs (NVP, ABC, etc.).
(c) History taking:
­ Duration of illness, characteristics of onset (acute, subacute)
­ Symptoms from organs and systems: headache, diarrhea, cough, skin
eruption...
­ Medications used: CTX, ARV, other drugs
­ Previous history of OIs and other HIV associated conditions (potential
recurrence of OIs if secondary prophylaxis or ARV treatment not
given).
­ Previous history of drug allergy and other conditions.
­ Family history: TB and other communicable diseases
(d) Clinical examination:
­ Examine all organs and body systems; focus on affected organs.
­ If the children have low CD4 count, consider examination of the eyes
for lesions suggestive of CMV, toxoplasma.
(e) Find out causes of opportunistic infections, request lab tests and other
investigations to establish diagnosis and treatment (also see Section V:
Diagnosis and treatment of common opportunistic infections in HIV infected
children).

 
107

2. Respiratory findings

Respiratory findings: cough, fever +/­ dyspnea (a)

Acute onset Yes Consider bacterial
Fever, productive cough pneumonia
Chest X ray: bilateral patchy opaque Antibiotic therapy (d)
No

No fever or mild fever, dyspnea, dyspnea, often

no rales, SpO2 <90%. Yes Consider PCP, treat
Take history and assess clinically (b)  CXR: diffuse infiltration with CTX (d)
Perform diagnostic tests (c)  Acute progression/severe immunodeficiency
­ Routine tests  
­ CXR, sputum exam and culture for AFB,  No
bacteria   Chronic or subacute onset
­ Other lab tests and investigations  Yes
Contact with TB source Primary lung TB (d)
CXR: enlarged nodes in hila or paratracheal
space, or lung infiltration, apical infiltration
No
Find out the cause No
Dry cough, clubbing finger, enlarged lymph Yes
Treat presumptively as
nodes, hypoxemia lymphocytic interstitial
CXR: interstitial, nodular and reticular infiltration pneumonitis (d)
Yes
No
Treat accordingly (d)
High fever, dyspnea, dyspnea, unremarkable Yes Viral pneumonia:
crackles or bronchial rales Supportive care
CXR: interstitital lesions

No improvement observed:
­ Re­assess clinically and repeat essential
tests (Chest XR, sputum, node aspirate
  etc...)
108

­ Consider TB treatment
­ Consult or refer to a higher level
Instructions:
(a) Causes:
­ Common causes: Bacterial pneumonia, PCP, primary lung TB, lymphocytic
interstitial pneumonitis, viral pneumonia
­ Other causes: fungal diseases, non­infectious causes
(b) Considerations in history taking and clinical examination:
Taking history: Clinical examination:
­ Acute, subacute onset ­ Respiratory failure: dyspnea, cyanosis
­ Dry or productive cough ­ General conditions: fever, weight loss,
­ Accompanied findings: eruption, enlarged lymph nodes, clubbing
fever, weight loss, cold fingers, etc...
sweating… ­ Respiratory examination: crackles,
­ TB history of the patient fremitus…
and his/her family ­ Other findings: mental­physical
development, manifestations of
immunodeficiency such as oral thrush,
cachexia…

(c) Diagnostic tests: Based on clinical signs & symptoms and history
­ Routine tests, CD4 cell count,
­ Chest X ray; sputum AFB; sputum microscopy and culture for
other bacteria.
­ Blood culture in cases of fever
­ Pleural tapping in cases of pleural effusion and lymph node
aspirate in cases of lymphadenopathy for lab tests
­ Chest CT scan if available
(d) See also Section V: “Diagnosis and treatment of common opportunistic
infections in HIV infected children”

 
109

3. Neurologic findings
�

Children with neurologic

abnormalities (a)

Yes
Static or Treat as HIV encephalopathy
progressive motor Static or
progressive HIV Supportive care
or cognitive ART
encephalopathy

No
CSF suggests specific
infections (c): Yes
Yes
Acute Yes Bacterial meningitis Treat for the cause (d)
Lumbar
episode Cryptococcal meningitis
puncture ? TB meningitis
Other causes
No
No No
Yes
Suspect brain hemorrhage
Refer to a higher Increased or occupying mass lesions
level or treat CSF pressure
presumptively as
bacterial meningitis
(d) No
Supportive care

Treat as HIV encephalopathy

(d) and start ART

 
110

Instructions:
(a) Definition: Neurologic diseases in children include:
­ Progressive encephalopathy: Progressive decline in motor, cognitive or
language functions, evidence of loss or increasing delay in achieving
developmental milestones; onset can be as early as the first year of life
but can occur at any time.
­ Static encephalopathy: Motor dysfunction and other developmental
deficits of varying severity that is non­progressive as documented on
serial neurological and developmental examination.
­ HIV static encephalopathy is defined when no other causes of
developmental deficits/neurologic dysfunction found, such as premature
delivery, asphyxia at birth, use of drugs or alcohol in pregnancy.
­ Acute infection: acute onset with seizures, focal motor deficits and
meningeal syndrome (such as in bacterial meningitis, cryptococcal
meningitis, TB meningitis).

(b) Acute manifestations can occur in previously healthy HIV infected children
or superimposed on HIV encephalopathy.
(c) Relied on lab results of CSF for biochemistry, cytology, bacterial and fungal
examination and culture to determine
(d) Causes and treatment: See also Section V: “Diagnosis and treatment of
common opportunistic infections in HIV infected children”.

 
111

4. Persistent diarrhea (a)

Take history, examine

clinically (b, c)
Rehydrate and correct electrolytes’
disturbance; counsel for proper diet; treat
malnutrition if exists

Stool exam&culture for Yes Yes

causes, other Find out the Treat according
tests&investigations (d) cause the cause (e)

No No

Suggestion of bacterial
invasive agents: bloody Treat
stool exploratively for 5
No days
Yes
Suggestion of viral diarrhea Treat supportively Yes
Complete
Improved
the
No treatment
Yes
No
Suggestion
No of Treat supportively,
malabsorption, improvement proper diet
with antisecretary treatment Investigate
further for
No causes
Yes Consider causal
Suggestion of diarrhea due Treat with drugs
against the parasites treatment
to parasites or protozoa
or protozoa ART
Prophylaxis with
CTX

 
113
Instructions:

(a) � Definition: Chronic diarrhea is defined as liquid stools of more than thrice
per day, lasting for over 14 days

(b) � Taking history:

­ Frequency of bowel each day, characteristics of stools
­ Accompanied symptoms: fever, abdominal pain, location and
characteristics of pain
�
­ Nutritional history of the child.
�
­ History of TB and other communicable diseases in the family
�
(c) � Clinical examination:
­ Evaluate general condition and dehydration and nutrition

­ Evaluate developmental status

­ Systemic findings: fever, lymphadenopathy, weight loss;

­ Examine respiratory and circulatory systems

­ Examine the abdomen: tenderness, ascites, hepatosplenomegaly,

enlarged lymph nodes in the abdomen

(d) � Lab tests and investigations:

­ Stool microscopy; look for
o Red and white blood cells (invasive diarrhea due to shigella
and other kinds of bacteria); protozoan parasites (amoeba,
giardia, larvae of strongyloides, hookworm, helminthes eggs);
AFB (TB and MAC),
o cryptosporidium by formalin­ether concentration method and
modified acid­base staining , microsporidium and isospora by
trichromatic stain; if available
­ Blood culture if the child is febrile and diarrhea associated with
septicemia due to bacteria suspected
­ Chest X ray, sputum examination if respiratory findings or suspected
TB
­ Abdominal ultrasound to confirm hepatosplenomegaly,
lymphadenopathy and ascites:

(e) � Causes and treatment: See also Section V: “Diagnosis and treatment of
common opportunistic infections in HIV infected children”

 
114

5. Wasting and Failure to Thrive

�

Definition: Moderate failure to thrive: weight = 60­80% of normal for age/height; severe failure to thrive: weight = <60% of normal
for age/height, or weight 60­80% of normal for height if edema present
Common causes: recurrent or occult infections; oral or esophageal candidiasis, or other pharyngeal infections, inability to provide
adequate amounts of food/calories; malabsorption and diarrhea, vomiting, chronic HIV infection, TB or MAC peritonitis
History: Severity of weight loss, signs of occult infection, history of diarrhea or vomiting, feeding practice.
Clinical Exam: Weight and height, complete exam looking for signs of occult infection 
Initial support: Hydration and nutritional support. Begin evaluation for ARV if the child is eligible.

History of inadequate History of thrush Child critically History of fever

caloric intake? or oral ulcers? malnourished or or diarrhea?
dehydrated?

Give feeding trial for 7 Treat for candida or Hospitalize to give

days with increased HSV (if ulcers) nutritional support,
caloric and vitamin fluid replacement,
supplementation vitamins and minerals

If improved, continue
Perform complete blood count with differential WBC,
treatment with close
albumin, blood cultures, CXR, rule out TB, stool
monitoring
studies for bacteria, ova and parasites. Evaluate as
No improvement for patients with diarrhea, fever. Abdominal ultrasound
may reveal enlarged liver and spleen.

­ Consider hospitalization for dietary support.

�
Treat for
­ Re­evaluate for occult infection.
� No Causes found? Yes causes
­ Consider ARV treatment if eligible
�  
115
 V. DIAGNOSIS AND TREATMENT OF COMMON OPPORTUNISTIC INFECTIONS IN HIV INFECTED CHILDREN
�

OI Clinical features Diagnosis Treatment*

Fungal diseases

Candidiasis The disease usually occurs in • Based on clinical features Oral candidiasis:
severe stage of immunodeficiency
with severe, refractory course and • Esophagoscopy: indicated if the • Oral Fluconazole 3­6 mg/kg once daily
is prone to relapse. symptoms not improved with for 7­14 days;
antifungal treatment
• Oral, pharyngeal and esophageal • Topical application: Daktarin oral gel
candidiasis: multiple white, easily • Microscopic exam for fungi when (miconazole) or Nystatin 5 times daily for
removable patches, the patient not responding to the 7­14 days.
pseudomembranous plaques treatment.
Esophageal candidiasis:
located on the tongue, gums,
• Culture if the clinical features are
buccal and pharyngeal mucosa. If ­ Fluconazole 3­6 mg/kg once daily for 14 ­ 21
atypical.
the lesions spread to the pharynx days or
and esophagus, the child often
has dysphagia and/or painful ­ Ketoconazole 5mg/kg/day orally in 1­2
swallowing. divided doses for 2­3 weeks

Invasive candidiasis: Amphotericin B 0.5­1.5

mg/kg/day for 2­3 weeks

Cryptococcosi Cryptococcosis is rare in children, • CSF: clear, with high opening • Induction treatment: indicated for severe
s and is more common in children > 6 pressure; glucose and protein can meningitis (patients with altered
years be normal; cell count slightly consciousness, brain edema, positive CSF
elevated with lymphocytes microscopy for fungi, etc)
• Meningitis: fatigue, fever, predominate. Staining with India
persistent headache, nausea, ink for fungi. Preferred regimen: Amphotericin B 0.7­1.5
vomiting, alteration of mental mg/kg/day x 2 weeks

 
116

 status, epilepsy, coma; occult • CSF, blood and tissues culture for • Consolidation phase: Fluconazole 5 – 6
meningeal signs, possible visual fungi. mg/kg/day x 8 weeks
disturbance, hearing loss, etc...
• Skin biopsy for microscopy and • Maintenance therapy: Fluconazole 3
• Skin eruption: nodules­papules culture for fungi. mg/kg/day or Itraconazole 3 mg/day.
with central necrosis, ulcerative
papules, pustules. • Cryptococcal antigen in serum. • Discontinue when the patient on ART and
CD4 count > 200 cells/mm3 ≥ 6 months
• Pneumonia: diffuse interstitial
pneumonia. Mild cases can be started immediately with
oral fluconazole
• Other organs involvement: bone,
kidney, liver, lymph nodes.

Penicilliosis The disease usually occurs when • Based on clinical features if patients Combined therapy: Amphotericin B
the patient is severely present with fever and typical skin intravenously, 0.7­1.5mg/kg/day for 2 weeks,
immunocompromised. Features: lesions followed by itraconazole 5­ 6 mg/kg twice
daily 8 weeks.
• Fever, enlarged lymphnodes, • Direct microscopy for fungi with
hepatosplenomegaly, weight specimens taken from the skin, • Maintenance treatment: Itraconazole 3
loss, anemia. bone marrow, lymph nodes. mg/day lifelong. Discontinue the
maintenance therapy when the patient on
• Skin rash: umbilical necrotic • Blood culture and culture of above ART and CD4 count > 200 cells/mm3 ≥ 6
papules; mainly distributed on specimens in Sabouraud media at 25­ months.
the head, face, upper trunk or 37oC.
throughout the body.
• Skin biopsy.

Pneumocystis The disease commonly occurs in Characteristic clinical features • Preferred regimen: TMP ­ SMX
Pneumonia infants aged less than 1 year, 20mg/kg/day (based on TMP) in 3­4
(PCP) usually with severe clinical course Definitive diagnosis: microscopy of divided doses (every 6­8 hours) for 21
sputum (induced sputum for high
 
117

 and high mortality risk. sensitivity) or days

bronchial/bronchioaveolar lavage fluid
• Acute or subacute onset with for P.jiroveci; staining methods: • Alternative regimen: Clindamycin 20 – 40
fever, cough, tachypnea, Giemsa, silver impregnation, mg/kg/day in 4 divided doses
cyanosis; physical exam reveals immunofluorescence. intravenously + Primaquin 15­ 30mg/day
crackles in the base of both orally.
sides. Atypical symptoms may
be present as cough without • Supportive treatment with steroids in
fever, dyspnea, anorexia, weight case of respiratory failure (PaO2< 70 mm
loss. Hg). Prednisone 2mg/kg/day in 2 divided
doses for 5 days, then 1 mg/kg/day for 5
• Lab tests: commonly moderate days, followed by 0.5 mg/kg/day from day
to severe hypoxemia (low PaO2), 11 to day 21, then stopped if the child is
leukocytosis, elevated LDH > 2 stable.
UNL.

• Chest XR: bilateral diffuse

interstitial infiltration, may
present with lobar infiltration,
miliary pattern or normal.

Protozoan diseases
Toxoplasmal Toxoplasmal infection in children • Serology for IgM, IgA, IgE in the Initial treatment
encephalitis may be antenatal (congenital) or first 6 months and for IgG in
postnatal. children over 12 months of age. • Congenital toxoplasmosis: Co­trimoxazole
Serology can be negative in 10­15 mg TMP/kg/day intravenously or
Early symptoms of toxoplasmosis children with toxoplasmal orally, or Pyrimethamine 2 mg/kg/day orally
include fever, sore throat, myalgia, once daily for 2 days, then 1 mg/kg/day
encephalitis.
enlarged lymph nodes, skin eruption daily for 2­6 months, then 1 mg/kg/day 3
and hepatosplenomegaly; • Isolation of the agent or PCR of times per week + Sulfadiazine 50 mg/kg/day

 
118

 blood, CSF, amniotic fluid or orally in 2 divided doses + Acid folinic 10­25
tissues involved. mg/ day. Duration of treatment is decided by
Late symptoms include physicians experienced in treatment of
encephalopathy, fever, confusion, • Diagnostic imaging (cerebral CT, toxoplasmosis.
seizures and retinal involvement. MRI) can show specific lesions of
abscess • Postnatal toxoplasmosis:

Preferred regimen: Co­trimoxazole 10­15

mg TMP/kg/day intravenously or orally, or
Pyrimethamine orally, induced dose
2mg/kgBW/day for 3 days, the decreased
dose 1mg/kg/day + acid folinic orally 10­25
mg/day + sulfadiazin orally, 120mg/kg/day in
4 divided doses for 3­6 weeks.

Alternative regimen: Pyrimethamine +

clindamycin

Maintenance treatment:

• Cotrimoxazole 5mg/kg/day (based on TMP)

• Pyrimethamine 1 mg/kg/day + folinic acid 5

mg/kg 3 times/week + sulfadiazin 85­120
mg/kg/day in 2­4 divided doses or

• Pyrimethamine + folinic acid + clindamycin

Crypto­ Subacute or chronic watery diarrhea Modified acid­fast staining of stool ART is the only effective treatment that
sporidiosis often associated with cramps, reveals small oocyst (4–6 µm in controls persistent cryptosporidiosis.
nausea and vomiting. diameter).
Supportive care includes rehydration,
 
119

 correction of electrolyte abnormalities and

nutritional supplementation.

Nitazoxanide is approved for treatment (aged

1–3 years: 100 mg twice daily, aged 4–11
years: 200 mg twice daily)

Bacterial diseases

Tuberculosis ­ Carefully history taking for + Tuberculin test (Mantoux): TB treatment for HIV infected children:
course of illness, source of positive reaction (≥ 5mm)
infection ­ Regimen: 2RHZE/4RH (per National TB
+ Imaging diagnosis: Chest X­ray, program’s protocol)
­ Clinical examination: CT, MRI, ultrasound , etc
­ Severe tuberculosis (miliary TB, meningitis
+ Prolonged cough, prolonged + Lymphnode, abscess aspiration TB, bone/joint TB), supplement of
fever for > 2 weeks, weight or biopsy: Streptomycin for 2 months of intensive
loss (or no weight increase), treatment and prolong period of
sweating, …. + CSF, pleural, peritoneal tapping maintenance therapy.
andanalyses
+ Cervical lymphadenopathy, ­ Consider interaction between rifampicine
no pain, with/without fistula + M.tb detection (by different and nevirapine (replace with Efavirenz),
methods, such as microscopy for monitor ALT level during treatment
+ Subacute meningitis, with AFB, PCR, culture, etc.) in
increased intracranial specimen , such assputum, ­ TB drugs
preasure, not responding to gastric /bronchial wash, body
conventional antibiotics fluids, lymphnode aspiraton, pus Drugs Dose
from abscess, etc
+ Pleural, peritoneal, or Daily 3 times/week
pericardial effusion
mg/kg mg/kg
+ Arthritis, spondilitis

 
120

 Isoniazid 5 (4­6) 10 (8­12)

Rifampicin 10 (8­12) 10 (8­12)

Pyrazinamid 25 (20­30) 35 (30­40)

Ethambutol 20 (15­25) 30 (25­35)

Streptomycin 15 (12­18) 15 (12­18)

Side effects of ­ Abscess at injection site, Aspiration of lymphnodes for ­ Treat with at least 4 drugs: Isoniazid,
BCG in HIV enlarged lymphnodes at histopathology, culture if possible Rifampicin, Pyrazinamid, Ethambutol,
infected vaccination side. Systemic Ofloxacin or Ciprofloxacin.
children manifestations with high
(BCGit) mortality rate (75%) ­ Treat for at least 9 month and consider
ARV treatment.

Atypical Fever, night sweats, weight loss, Isolation of the causative Combination treatment:
Mycobacterial fatigue, chronic diarrhea and microorganism or histopathology
complex abdominal pain. Clarithromycin 7.5 – 15mg/kg twice daily
(MAC) (maximum 500mg/dose) + Ethambutol 15 –
Laboratory findings: neutropenia, 25mg/kg once daily (maximum 1000mg) +
increased alkaline phosphatase or Rifampicin 10­20 mg/kg once daily.
lactate dehydrogenase (LDH)

Severe and Pneumonia is a common cause of Characteristic clinical features. Frequently used antibiotics as below:
recurrent deaths in children with HIV/AIDS. Investigations: elevated WBC and
bacterial Septicemia, empyema, neutrophils; chest X ray, sputum ­ Ceftriaxone 80–100mg/kg/day in 1­2 divided
infections osteomyelitis, purulent adenitis, microscopy and culture, blood doses
cellulitis, meningitis, etc. can occur. culture, pleural tapping and pleural ­ Cefotaxime 150–200mg/kg/day in 3­4 divided
fluid microscopy and culture for doses

 
121

 • Clinical features: bacteria if available. � When enteric Gram negative bacteria are
suspected, use:
Fever accompanied by
manifestations from involved ­ Ceftazidime 150 – 200mg/kg/day in 3­4
organs such as cough, dyspnea, divided doses
meningeal signs, red swelling
lymphnodes… ­ Ciprofloxacin 20 – 30 mg/kg/day in 2 divided
doses
• Lab findings: WBC often not
� When methicilline resistant staphylococcal
elevated, diagnostic tests for organ
infection is suspected:
involved as chest x ray, CSF
­ Vancomycin 40 – 60 mg/kg/day in 3­4 divided
Blood, CSF and pleural fluid
doses
should be cultured for causative
agents. ­ Clindamycin 10 – 20 mg/kg/day in 3­4 divided
doses

� CTX must be combined if PCP cannot be

ruled out

� If no improvement after 7–10 days, lab tests

for TB and fungal infections must be
performed

Lymphocytic Commonly seen in older children Characteristic clinical manifestations Transient improvement occurs with
interstitial with HIV infection, rarely causing prednisolone 1­2mg/kg/day (if PaO2 < 85­90
pneumonitis mortality but has persistent course Chest X ray: pulmonary infiltrations mm Hg); taper the dose after clinical response.
(LIP) and can cause chronic dyspnea. as in TB or PCP
Gradual onset with following − Symptoms usually recur quickly after
manifestations: discontinuation of corticosteroid unless the
patient has been given ART.

 
122

 − Dry cough, dyspnea, finger − Do not use prednisolone in case

clubbing, parotitis, concomitant conditions for which
lymphadenopathy corticosteroids are contraindicated

− Hypoxemia, especially with

concomitant respiratory infections

− Lab findings: CXR with bilateral

reticulonodular interstitial infiltrates,
bronchiectasis

Viral diseases

Herpes zoster Zoster may occur when the TCD4 Clinical features often typical and not Acyclovir 20mg/kg orally 4 times per day for 7­
infection cell count is still relatively high. require supportive lab tests. 10 days.
(Zona)
Clustered vesicular eruptions with Apply topical antiseptics such as methylene
central crust, distributed within a blue, millian for controlling superinfection.
dermatome in one side of the body,
commonly on the intercostal areas,
chest, back and face, along the
path of a nerve.

The child often experiences burning

pain in affected area, sometimes
persistent even after the lesions
already resolve, also called
postherpetic neuralgia. Fever may
present.

 
123

 The condition is often difficult to

treat and frequently relapsed, may
appear in both sides and affect
multiple areas of the body

Herpes Skin and mucosa manifestations: • Based on clinical manifestations • Acyclovir orally 20 mg/kg 3 times per day
simplex vesicular eruptions in crops, quickly for 5­10 days for mild cases;
progressing to ulcerations; • Tzanck preparation for gigantic
frequently localized in or around the cells, viral culture or fluorescent • Intravenous Acyclovir 5 ­10mg/kg every 8
genital organs, can be found in antibody test, PCR, if possible. hours for 10 days for severe cases
rectum and colon, oral cavity and including encephalitis; or
perioral areas, occasionally
• Famciclovir 125 mg orally twice daily for 5­
spreading to esophagus causing
10 days;
dysphagia, odynophagia;
sometimes expanding to trachea • Topical application of methylene blue or
and bronchi. The disease is gentian violet for controlling superinfection.
generally more severe with frequent
relapses compared with HIV­
negative persons.

Herpes encephalitis: manifestations

are often nonspecific with focal
lesions in frontal­temporal lobes.

Cytomegalo­ Cytomegalovirus (CMV) disease Fundoscopy if retinitis suspected. • Preferred regimen for systemic disease and
virus (CMV) often occurs when CD4 < 50 retinitis: Gancyclovir 10 ­ 15 mg/kg/day
Brain biopsy, CSF, skin lesion, blood
cells/mm3. intravenously in 2 divided doses for 14 ­ 21
for viral culture or PCR.
days, then 5 ­ 10 mg/kg/day x 5­7
 
124

 Major manifestations of CMV Children with low CD4 count should days/week.
disease in children: retinitis, have eyes carefully examined to
esophagitis, hepatitis, pneumonia, assist in considering treatment for • Alternative regimen: Foscarnet 180
encephalitis, colitis; fever, failure to CMV or ARV and to prevent immune mg/kg/day in 3 divided doses for 14­21
thrive, developmental retardation, reconstitution syndrome days, then maintain 90­120 mg/kg/day.
hearing loss; anemia, • Retinitis in children > 3 years of age:
thrombocytopenia, elevated LDH. intraocular ganciclovir combined with
gancyclovir orally 90 mg/kg/day in 3 divided
doses.

• Maintain lifelong ganciclovir 5 mg/kg/day

intravenously after systemic disease.
Maintenance therapy for retinitis is
ganciclovir intraocular every 6­9 months +
ganciclovir orally 90 mg/kg/day in 3 divided
doses.

• Discontinue the treatment if ARV treatment

has been started and CD4 percentage >
15% for more than 6 months

* Pay attention to interaction between OI drugs and ARVs (see Annex 6)

�

 
125

VI. ANTIRETROVIRAL THERAPY

1. Goals and principles of ART

1.1. Goals of ART for HIV infected children:

­ To suppress the virus replication and maintain the viral load at a possible
lowest level in the blood.
­ To restore immunological function and help decrease the prevalence of
opportunistic infections (OI).
­ To improve the quality of life for the children and increase the survival.
­ To maintain normal growth for children physically and mentally.
1.2. Principles of ARV treatment:
− ART is part of comprehensive package of medical care and socio­
psychosocial supports for children living with HIV/AIDS.
− Any ART regimen should must include at least 3 drugs.
− ART is lifelong treatment and the children should adhere absolutely to
therapy to ensure treatment efficacy and avoid drug resistance.
− HIV infected children commencing ART should continue prophylaxis for
opportunistic infection (OI) when the immune system has not been
reconstructed.
1.3. ARV drug classes used in Vietnam:
− Nucleoside and nucleotide reverse transcriptase inhibitor (NRTI)
�
− Non­nucleoside reverse transcriptase inhibitor (NNRTI)
�
− Protease inhibitor (PI)
�
Details for common ARV drugs and their usage, see Annex 3.
�
2. Criteria for initiating ART

Antiretroviral Therapy is initiated on the basis of diagnostic status of HIV

diagnosis, age, clinical and immunological staging of the children.

1. �Children with confirmed HIV infection:

• Children < 12 months: ART should be provided immediately regardless

clinical staging and CD4 cell count

• Children > 12 months, ART is indicated when:

�

­ Clinical stage 4, regardless of CD4 count.

�

126

 
 ­ Clinical stage 3, regardless of CD4 count; children with TB, LIP,
oral hairy leukoplakia (OHL) and thrombocytopenia, should be
treated for these conditions first and ART can be delayed if CD4
count is still above level of “severe immunodeficiency” by age. If
CD4 count is unavailable, consider ART.

­ Clinical stage 2 and CD4 cell count (or TLC) below the level of
“severe immunodeficiency” by age

­ Clinical stage 1 and CD4 cell count below level of “severe

immunodeficiency” by age

2. Children under 18 months of age who have not diagnosed as HIV

infected by virological testing, but are clinically diagnosed with severe
HIV/AIDS disease.

3. Preparation for readiness to commence Antiretroviral Therapy

The preparation for readiness to commence ART must be started from

the time the patient first presents to the treatment facility. The contents of the
readiness preparation should proceed at every patient visit so that the ART
can be initiated immediately should the patient fulfill the criteria for initiating
the treatment.
3.1. Pre­ART assessment:
The following is the content of the Pre­ART assessment for the HIV
infected children who fulfill the clinical and/or immunological criteria for
initiating ART:
­ Re­assess clinical stage and immunologic status (% of CD4 cell count or
total lympho count if CD4 is unavailable).
­ Screen for TB and other opportunistic infections; consult with other
specialized services (TB, dematology, etc…) if needed. Provide treatment
for TB and acute OIs, if present.
­ Perform basic laboratory tests and those necessary for selecting ART
regimens: CBC/Hgb and liver enzymes (ALT).
­ Take previous ART history of the mother and her child, if any, the reason
for use (as prevention of mother­to­child transmission or treatment for the
mother), specific regimen, treatment adherence, and the course of disease
with the treatment.
­ Assess nutritional status, family situation of the children, treatment
willingness of the family/care givers.
­ Choose the suitable ARV regimen for the children
127

 
­ Inform the family/care givers about the plan for ART­readiness preparation
­ Provide Co­trimoxazole prophylaxis, other prophylaxis if indicated and
available.

3.2. Education and Counseling prior to ART

Provide counseling to the parents/care givers and the children (if grown up
enough) on “Understanding of Antiretroviral therapy” including:
­ Course of HIV infection, ARVs and benefits of the treatment

­ Importance of treatment adherence and measures for strengthening

adherence

­ Treatment regimen, how to divide or measure the drugs, how to store drugs

­ How to manage vomiting after taking drugs, drug side effects and its
management

­ Plan for care and follow­up at the treatment facility or at home

3.3. Assessment for treatment readiness

­ Assess the parents/care givers about “Understanding of Antiretroviral
therapy” to ensure that the children will be given drugs exactly as
requirements of treatment. Provide training and counseling again if the
parents/care givers show inadequate understanding. Counseling period can
be shortened in case of severe conditions requiring early initiation of ART.

­ Verify other issues such as place of residency, ability to contact as needed,

community supports.

­ The parents/care givers sign in the informed consent forms for ART
participation of the children.

­ Note: If the children need to be given treatment immediately, dispense

ARVs for treatment and plan counseling for subsequent follow­up visits, or
hospitalize the children.

3.4. Initiation of Antiretroviral Therapy

­ Prescribe a first­line regimen for all children newly starting antiretroviral

therapy; take into consideration history of exposure to NVP (the mothers or
the infants have been given PMTCT with NVP containing regimen within
previous 12 months) to ensure appropriate choice of regimen.
128

 
­ Dispense the ARVs and instruct the parents/care givers about the
treatment drugs, how to take the drugs, the schedule of drug dispensing
and follow­up visits. Ensure that the parents/care givers have a plan to
comply with therapy and know how to manage if facing difficulties.
­ Instruct the parents/care givers how to store drugs at home. Cold storage is
required exclusively for suspensions of d4T and LPV/r.
­ Choice of Pediatric formula of ARVs (suspension or tablet) is based on age
or body weight of children. Infants under 10 kg of body weight should be
given syrup; tablet formula with fixed dose combination can improve
treatment adherence of the children
­ Dosage calculation is based on body weight or surface area of children
(see Annex 4). Calculation is needed for choosing appropriate dosage in
accordance with infant's body weight; an ARV tablet should not be divided
into less than a half of the tablet.
­ Consider drug interactions when selecting regimen (see Annex 5).
4. First­line Antiretroviral Regimens:

4.1. Regimen for infant newly starting ART (exclude those have exposed
to NVP through PMTCT intervention wihin previous 12 months)
4.1.1 Preferred regimen:
AZT + 3TC + NVP
Indications: for all chidren initiating ART, who have never exposed to NVP or
have exposed to NVP (through PMTCT intervention) for more than 12 months
Note:
o Lead­in NVP dose should be half of normal dose, increase to normal
dose after 2 weeks of treatment
o Take drugs every 12 hours. Drug can be taken before or after meal
o Measure Hgb and ALT level prior to ART, after 1 month and then every
6 months or whenever anemia or hepatitis is suspected.
o Do not start this regimen when children have Hgb < 80 g/l; If during
treatment Hgb < 70 g/l, AZT should be replaced
o Cautious when using NVP for children with ALT > 2,5 upper normal
limit and children on TB treatment with rifampicin

4.1.2. Alternative regimens:

a. d4T + 3TC + NVP
129

 
Indications: children who have contraindications for or intolerance with AZT.
Note:
o Lead­in NVPdose should be half of normal dose, increase to normal
dose after 2 weeks of treatment
o Take drugs every 12 hours. Drug can be taken before or after meal
o Measure Hgb and ALT level prior to ART, after 1 month and then every
6 months.
o Cautious when using NVP for children has ALT > 2,5 upper normal
limit and children on TB treatment with rifampicin

b. AZT + 3TC + EFV

Indications: children with contraindications for or intolerance with d4T and
NVP, or on TB treatment with rifampicin, children over 3 years of age and
weighed > 10 kg .
Note:
o Take AZT + 3TC every 12 hours, EFV should be taken one time at
night, 2­3 hours after meals.
o Measure Hgb prior to ART, after 1 month and then every 6 months or
whenever anemia is suspected.
o Do not start this regimen when children has Hgb < 80 g/l; If during
treatment Hgb < 70 g/l, AZT should be replaced
o Do not start this regimen for children under 3 years of age or weighed
less than 10 kg or pregnant adolescent at first trimester, children with
mental disorders (present or previous problems).

c. d4T + 3TC + EFV

Indications: children over 3 years of age and weighed > 10 kg with
contraindications for or intolerance with NVP, or on TB treatment with
rifampicin.
Note:
o Take AZT + 3TC every 12 hours, EFV should be taken one time at
night, 2­3 hours after meals.

130

 
 o Do not start this regimen for children under 3 years of age or weighed
less than 10 kg, or pregnant adolescent at first trimester, children with
mental disorders (present or previoushistory of).

d. Triple NRTIs Regimen: AZT/ d4T + 3TC + ABC

Indications: use only for children with intolerance with or allergic to NVP and
EFV, or because of drug interaction (rifampicin). This regimen should be used
restrictively.

4.2. Infants under 12 months of age who have exposed to NVP (the
mothers or the infants have received NVP containing PMTCT regimen):
4.2.1. Preferred regimen: AZT + 3TC + LPV/r
Indications: Use this regimen to all children under 12 month of age who have
exposed to NVP through PMTCT intervention.
4.2.2. Alternative regimens:
a. d4T + 3TC + LPV/r
�
Indications: children with contraindications for or intolerance with AZT.
�
b. ABC + 3TC + LPV/r
�
Indications: children with contraindications for or intolerance with AZT, d4T
�
c. AZT + 3TC + NVP or d4T + 3TC + NVP
�
Indications: if LPV/r is unavailable
�
5. ARV drug side effects and its management

5.1. ARV toxicity: The severity of ARV­related drug toxicity in children is

divided into 4 grades: mild, moderate, severe and severe life­threatening, as in
adults. Grading of ARV side effects in children is displayed in the Annex 7.
­ Grade 1 (Mild): symptomatic treatment, change of therapy not required.

­ Grade 2 (Moderate):

o If children have lipodystrophy or peripheral neuropathy (d4T),

substitute the offending drug

o Other side effects: consider continuation of ART and symptomatic

treatment, consider substitution of drug if condition is not improved.

­ Grade 3 (Severe): Do not stop ARV, substitute drug that cause side
effects.
131

 
 ­ Grade 4 (Severe life­threatening):

o Immediately discontinue ARV drugs, manage the medical event

o Restart ART, when condition is stabilized, substitute the offending

ARV with other.

Note when managing ARV drug toxicity:

1. Determine the severity of the toxicity based on clinical signs/symptoms

and laboratory testing

2. Evaluate concurrent medications and verify if the toxicity is attributable

to an ARV or other drugs taken at the same time.

3. Exclude other disease’ processes that can result in worsened situation.

4. Manage the adverse event according to severity:

5. Emphasize importance of treatment adherence.

5.2. Management of common side effects of ARV drugs

The severity of side effects should be assessed depending on clinical
manifestation and laboratory test in order to provide appropriate management.
Table 8: Management of some ARV serious side effects in children
Clinical manifestations Laboratory Management

Severe rash/Stevens–Johnson syndrome (NNRTI class, particularly NVP, less

common with EFV)

­ Rash usually occurs ­ Elevated ­ If mild or moderate rash, ART

during the first 6­8 aminotransferase can be continued without
weeks of treatment evels (see Annex interruption but under close
7) observation
­ Rash at grade 1,2
­ For severe rash: substitute
­ Rash at grade 3 toxic drug, provide
­ Rash at grade 4 ­ life­ symptomatic treatment
threatening (Stevens– ­ For life­threatening rash:
Johnson syndrome or discontinue all ARVs and
toxic epidermal provide symptomatic
necrolysis treatment.

Once symptoms resolve,

132

 
 restart ART, substitute NVP
with a PI­based regimen or
triple NRTI (see Section IV,
item 4). NEVER using NVP for
children again.

Severe anemia, leucopenia (AZT)

Assess status of: ­ Decreased Give blood transfusion if needed;

hemoglobin and discontinue AZT if Hb < 70g/l and
­ Skin lesions, neutrophil cell substitute with d4T or ABC
membrance count (see
­ Heart beat Annex 7)

­ Functional status
(fatigue)

Severe and chronic CNS toxicity: due to EFV

Sleep disturbance, Lasting for 2­4 Substitute with NVP

depression, behavior weeks
change

Acute hepatitis due to NNRTI class, particularly NVP, more rarely EFV; NRTIs
or PIs

Usually occurs within 6­8 ­ Increased Depending on severity:

weeks transaminase
and bilirubin ­ Monitor and provide
­ Jaundice level (see symptomatic treatment if at
Annex 7) grade 1 or 2
­ Liver enlargement
­ Substitute toxic drug if at
­ Gastrointestinal grade 3 (see Section VI, item
symptoms 10)
­ Fatigue, anorexia ­ If at grade 4 – life­threatening,
­ May have discontinue all ARVs and
hypersensitivity monitor; once symptoms
component (rash, resolve, either
fever, systemic o Restart ART by changing
symptoms) to an alternative ARV
(substitute NVP by EFV)
or

o Restart current ART

regimen under close
observation; if symptoms
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 recur, substitute the
offending drug with an
alternative ARV

Acute pancreatitis (NRTIs, particularly d4T, ddI; rarely 3TC)

Assess for: ­ Increased If at grade 4 – life threatening:

pancreatic amylase
­ Nausea and vomiting and lipase level ­ Discontinue all ARVs until
(see Annex 7) symptoms resolve
­ Abdominal pain
­ If possible, monitor serum
­ May accompany lactic pancreatic amylase, lipase
acidosis
­ When symptoms resolve,
restart ART, substitute the
offending drug with an
alternative NRTI, preferably
one without pancreatic toxicity

Hypersensitivity reaction (ABC or NVP)

­ ABC: progressive ­ Increased If at grade 3: replace toxic drug

worsening of transaminase and provide symptomatic
symptoms soon after levels and treatment
starting ABC, usually eosinophil count
within 6–8 weeks. (see Annex 7) If at grade 4 – life threatening:
Children present with ­ Immediately discontinue all
fever, fatigue, ARVs and provide
myalgia, nausea, symptomatic treatment
vomiting, diarrhea,
abdominal pain, ­ When symptoms resolve,
pharyngitis, cough, restart ART, substite toxic
dyspnea; rash ARV (ABC or NVP) by others.
(usually mild)
­ NVP or ABC should NEVER
­ NVP: Systemic be readministered to the
symptoms of fever, patient
myalgia, arthralgia,
hepatitis, with or
without rash

Lipodystrophy (d4T; PIs)

Fat loss and/or fat ­ Elevated serum Monitor closely, especially after 6­
accumulation in specific triglycerides; 12 months of treatment

134

 
parts of the body: ­ Elevated serum If lipodystrophy occurs, substitute
cholesterol; d4T with ABC or AZT
­ Fat deposit in
abdomen, buffalo ­ Low HDL levels Substitute an PI with NVP or EFV
hump, breast
hypertrophy ­ Hyperglycemia

­ Fat loss from limbs,

buttocks and face
occurs to a variable
extent

Severe peripheral neuropathy (d4T, ddI; rarely 3TC)

­ Pain, tingling, ­ None Monitor closely, especially after 6­

numbness of hands or 12 months of treatment
feet; inability to walk
Substitute d4T with AZT or ABC
­ Distal sensory loss

­ Mild muscle weakness

and areflexia can
occur

Lactic acidosis (NRTI class, particularly d4T)

­ Generalized fatigue ­ Increased anion Severe: replace toxicity drug and

and weakness gap provide symptomatic treatment

­ Gastrointestinal ­ Lactic acidosis Life­threatening:

symptoms (nausea,
vomiting, diarrhea, ­ Raised ­ Discontinue all ARVs and
abdominal pain, aminotransferas provide symptomatic
hepatomegaly, e, CPK, and treatment
anorexia, poor weight LDH levels
­ When symptoms resolve,
gain and/or sudden restart ART, substitute d4T
unexplained weight with ABC or AZT
loss)

­ May present with

hepatitis or
pancreatitis

­ Neurological
symptoms (including
motor weakness)

135

 
6. Monitoring Antiretroviral Therapy

− Children with ART should be followed and dispensed drugs as

scheduled every 1­2 months.

− Children at the beginning of ART should have frequent follow­up visits

for more counseling, adherence support and drug toxicity monitoring.
When the children exhibit good adherence and tolerance with the
regimen, their clinical conditions improved, the time between the visits
can be prolonged. More frequent visits should be scheduled in case
children have new opportunistic infections, poor adherence, or need
drug substitution .

− At each follow­up visit, the children should be evaluated for clinical

course, mental and physical development, occurrence of infectious
diseases, drug side effects, and assessed for treatment adherence,
provided with necessary counseling, support and testing.

6.1. Clinical monitoring

At each follow­up visit, monitor the the children for clinical course, identify and
manage the drug side effects or the occurrence of new opportunistic infections
as specified follows:
− Assess milestones of physical and mental development
− Monitor clinical signs and symptoms associated with drug side effects,
detect new or recurrent opportunistic infections; differentiate immune
reconstitution or treatment failure. Hospitalize for monitoring and treatment
or seek for consultation and referral as needed.
− Assess possibility of pregnancy for substituting ARV if indicated in case of
female adolescents (not using EFV in the 1st trimester of pregnancy)
6.2. Laboratory monitoring
Table 9: Laboratory monitoring during ART in children
Before During treatment
Contents initiatio
4 6 12 Every
n of
week month month 6
ART
s s s month
s

CD4 and % of CD4 � � � �

CBC/Hb, ALT � � � �

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CBC if using AZT containing
regimen � � � � �

ALT if using NVP containing

regimen � � � � �

Pregnancy test for female

adolescents � If suspected

Viral load (if available)

Note:
During ART monitoring, if patients present with abnormal signs and symptoms,
request immediately other necessary tests to timely detect the disease, make
diagnosis and provide treatment.

6.3. Adherence monitoring

The adherence to treatment should be assessed at each follow­up visit, based
on the following:
− Reports of the parents/care givers on administering drugs; ask the
parents/care giver questions on how to administer drugs and how to
manage when missing doses
− Counting the number of tablets left, examination for clinical and laboratory
improvement.
If the children are poorly adhere to treatment, reasons should be investigated.
The parents/care givers should be provided with adequate counseling on how
to overcome barriers to adherence and how to get timely supports to ensure
good adherence.

Instructions for missing ARV doses in children:

Right after recognizing missing a dose, first take immediately the missed
dose. Then calculate the time remained from this moment to the next regular
dose (in hours):
− If the remained time is more than 4 hours, take the following dose at the
scheduled time;

− If the remained time is less than 4 hours, DO NOT take the following
dose at the scheduled time, but wait until it reaches at least 4 hours to
137

 
 take the next dose.

− If more than 2 doses are missed in a week, report to doctors in charge for
more instructions.

6.4. Monitoring ART effectiveness:

Signs of good response to ART:
­ Good physical and mental development: gaining weight and height, being
physically active, meeting milestones for intelligent development.

­ Lower morbidity or absence of opportunistic infections.

­ Increase in CD4 count and CD4 percentage (often during 24 weeks after
starting ART)

If children respond well to treatment:

­ Continue ART regimen, modify ARV doses according children’s weight and
height

­ Regular counseling on and support adherence and nutrition

­ Drug dispensing and follow­up schedule

If children do not respond to treatment or have new clinical events:

­ Counsel again on adherence, assess treatment adherence and apply
measures to support treatment adherence

­ Counsel on nutrition, provide measures to enhance nutrition

­ Identify causes of no response to treatment or occurrence of new clinical

events (distinguish between drug side effects or drug interactions,
manifestations of immune reconstitution syndrome or treatment failure), do
tests if necessary and provide appropriate treatment.

7. Immune Reconstitution Inflammatory Syndrome (IRIS)

7.1. Definition:
Immune reconstitution inflammatory syndrome (IRIS) is characterized by
paradoxical worsening in the overall status of HIV­infected patients after the
initiation of antiretroviral therapy, due to recovery of immune system.

138

 
 The nature of IRIS is the overt inflammatory response of newly
reconstituted immune system to live microorganisms in the body or the
antigens of these agents.
Common manifestations of IRIS may include:
­ The occurrence of OIs, which were not recognized before starting ART
(such as TB, MAC, Cryptococcus meningitis, etc.)
­ The deterioration of OIs, which have been treated before starting ART.
­ The worsening of co­infections (hepatitis B and C) and autoimmune
diseases (psoriasis, dermatitis, etc.).
Timing: IRIS typically occurs within 2­12 weeks of initiation of ART, but can do
so at later time.

7.2. Incidence and risk factors

IRIS occurs in about 10% of patients initiating ART. Risk factors for IRIS
include:
­ Low CD4 cell count before the initiation of ART.
­ History of OIs before initiation of ART. The closer the time of ART initiation
to OI treatment, the higher risk of getting IRIS.
­ Use of potent ARV regimen (e.g. PI/r based regimen).
To prevent IRIS, patients should be screened and treated for OIs before
starting ART, particularly TB.
7.3. Manifestations of IRIS
Opportunistic infections and non­ infectious diseases associated with IRIS:
�
­ Mycobacterial diseases: TB (most common), MAC.
�
­ Fungal infections: Cryptococcus neoformans, Penicillium marneffei, PCP.
�
­ Viral diseases: CMV, Herpes simplex and herpes zoster, HBV, HCV,
�
progressive multifocal leukoencephalopathy
­ Protozoal diseases: toxoplasmal encephalitis, leishmaniasis
­ Non infectious diseases: psoriasis, thyroiditis
7.4. Diagnosis of IRIS
­ IRIS should be considered in children at more than 2 weeks after initiation
of ART who adhere well to therapy but present with clinical deterioration,
especially if patients have been in advanced stage of immunodeficiency

139

 
 with low CD4 count or OIs before starting ART. It is necessary to
differentiate from:
+ Drug side effects, or drug interaction
+ Manifestations of new opportunistic infections
+ Treatment failure (if patients have been on ART for more than 6 months).
7.5. Management of IRIS
­ Some IRIS may be mild and resolve without treatment, and no treatment is
required.
­ Continue ART if patients can tolerate the regimen.
­ Treat unmasking OIs according to causes; modify ARV regimen and doses
if there is an interaction between ARV and OI drugs (e.g. replace NVP with
EFV if patients are on rifampicin based anti­TB therapy and EFV is
available). Resume the original regimen after completion of OI therapy.
­ Discontinue ART temporarily only if patients are severe and cannot tolerate
the regimen. Restart ARVs when inflammatory syndrome is improved and
patients can tolerate the drugs.
­ Consider corticosteroid therapy in moderate to severe cases of IRIS. Oral
or parenteral prednisolone or methyl­prednisolone can be given at 0.5­1.0
mg/kg/day until the patients’ condition improves, then taper over 1­2 weeks.
­ Provide other interventions if necessary, such as surgical drainage of lymph
node abscess, surgical relief of bowel or trachea obstruction.

8. First­line treatment failure and second­line regimens

8.1. Treatment failure assessment:

a. Principles
­ Only consider treatment failure if children are on ART with triple regimen at
least for 6 months and have had good adherence.
­ Exclude IRIS or drug side effects, or conditions leading to poor drug
absorption.
b. Criteria for treatment failure:
Clinical failure ­ Lack of or decline in growth rate in children who initially
respond to treatment

­ Loss of neurodevelopmental milestones or development

of encephalopathy

­ Occurrence of new OIs or malignancies or recurrence of

140

 
 bacterial or fungal infections that are refractory to
treatment

Immunological
− CD4 count falls to or below the level of severe
failure
immunodeficiency by age after initial recovery response
Or
− CD4 count falls rapidly below the level of severe
immunodeficiency by age as confirmed by at least two
consecutive times of testing for CD4 count
Or
− CD4 count falls to or below the baseline CD4 count.
Or
− CD4 count falls below more than 50% of the peak level
during ARV treatment.
Note: Some conditions of clinical stage 3 such as lymph node TB, pulmonary
TB, bacterial pneumonia may not be considered indicators of treatment failure,
and do not require to change the regimen.

8.2. Management when suspecting treatment failure with first line

regimen:
Continue the first line regimen and re­assess treatment outcome after 1
month, if:
− The children are not complying enough with the regimen, provide
counseling and support for their families and caregivers.
− The children develop IRIS, or face drug side effects, or conditions leading
to poor drug absorption, find out causes and manage accordingly.
• Assess OI and concurrent diseases, timely treat and adequately provide
prophylaxis.
• Integrate clinical and CD4 criteria (or measure viral load) and seek for
adequate consultation for determining treatment failure and limit as
much as possible early switching while 1st line regimen is still in effect.

Table 10: Decision to switch to second line regimen with integrated

clinical, immunological criteria

New or Laboratory
recurrent tests to assess
Management
clinical treatment
events failure
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Clinical stage CD4 not • Do not switch
1 or 2 available
CD4 available • Closely monitor clinical events and CD4
if CD4 is closed to severe
immunodeficiency level

• Consider switching only if at least 2 CD4

results are below severe
immunodeficiency level by age

Clinical stage CD4 not • Consider switching

3 available
CD4 available • Closely monitor clinical events and CD4
if CD4 is closed to severe
immunodeficiency level

• Switch if CD4 is below severe

immunodeficiency level, especially if
children have ever had good
immunological response to ART

Clinical stage CD4 not • Switch

4 available
CD4 available • Switch;

8.3. Choice of second line regimen

Table 11: Switching from 1st line to 2nd line regimens

Choice of switching regimen

First line regimens Second line regimens

• AZT or d4T + 3TC + NVP • ddI + ABC + LPV/r

• AZT or d4T + 3TC + EFV

• AZT or d4T + 3TC + ABC • ddI + EFV + LPV/r

• ddI + NVP + LPV/r

• ABC + 3TC + NVP or EFV • AZT + 3TC (can add ddI) + LPV/r
• d4T + 3TC + LPV/r

Note on usage of 2nd line regimen:

142
 
− Alternative PI for LPV/r is ATV, which is used only for children over 6 years of
age
− See drug side effects in Annex 3, dosages of 2nd line regimen in Annex 4 and
drug interactions in Annex 5
− Didanosine (ddI): once or twice a day p.o.. Take the drug on empty
stomach, at least 1 hour before or 2 hours after meal.
− Lopinavir/Ritonavir (LPV/r): twice a day, every 12 hours; LPV/r capsule
should be taken on full stomach; for LPV/r tablets, no diet restriction.
− Atazanavir/Ritonavir (ATV/r): once daily p.o.

8.4. Monitoring children on second line regimen:

− Re­counsel care givers and children (for grown up children) to consolidate

adherence
− Carefully counsel on new regimens
− Pay attention to drug side effects: hypersensitivity (abacavir), renal failure
(tenofovir), pancreatitis (didanosine), hyperlipidemia and insulin resistant
diabetes mellitus (PI drugs)
− Monitor drug interaction when using LPV/r
− Assess clinical and CD4 response similarly to that of 1st line regimen

9. ART for children with TB

9.1. TB is diagnosed before starting ART

­ TB treatment should be given for children 2 – 8 weeks before initiating
ART.
­ ARV treatment for children on TB therapy with rifampicin:

+ Children ≤ 3 years and < 10kg of body weight: AZT/d4T +3TC + ABC;
or consider AZT + 3TC + NVP (if ABC is unavailable);
+ Children > 3 years and > 10kg of body weight: AZT/d4T +3TC + EFV
Note: NVP based regimen can be used again, when TB treatment with
rifampicin is completed.
9.2. TB is diagnosed during ART:
­ Determine if TB occurrence is IRIS. If yes, assess and mange IRIS.

­ Continue with ART and treat TB

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­ Selection of regimens:

o If children are on 1st line regimen without NVP, continue the regimen

o If children are on 1st line regimen with NVP

� Substitute NVP by ABC if children ≤ 3 years or <10 kg of body

weight; change NVP to EFV if children > 3 years and > 10 kg of body
weight and return to the standard d4T + 3TC + NVP regimen after
completion of TB therapy

� If ABC and EFV are unavailable, continue with NVP

o If children are on second line regimen with LPV/RTV: increase

ritonavir dose to the same as lopinavir.

10. ARV treatment for children with hepatitis coinfection

­ Testing for viral hepatitis B and C coinfection should be done if possible.

­ Prior to ARV treatment, measure liver enzymes as regulated.
• If liver enzymes are elevated ≥ 2.5 times of upper normal limit, consider
as follows:
o For children > 3 years of age: Preferably, use AZT (or d4T) + 3TC +
EFV
o For children < 3 years of age or if EFV is unavailable, use AZT (or
d4T) + 3TC + NVP; closely monitoring ALT level.
• Do not treat with NVP based regimen when ALT > 5 times of upper
normal limit.
­ During ARV treatment, closely monitor clinical course and liver enzyme
levels as regulated.
• If ALT ≤ 5 times of upper normal limit, continue the treatment
• If ALT level is between 5­10 times of upper normal limit, continue the
regimen but monitor closely liver enzymes every 1­2 weeks ;
• If ALT level is > 10 times of upper normal limit, in combination with
jaundice, replace NVP with EFV or PI

144

 
− 3TC has some effects on hepatitis B. In case changing regimen is needed,
3TC should be continued in the new regimen to avoid flare of hepatitis B.
− ARVs have no effect on hepatitis C.

145

 
 ANNEX

Annex 1 ­ Clinical and definitive diagnosis criteria of HIV/AIDS­related diseases in adults and adolescents

Diseases Clinical diagnosis Definitive diagnosis

Clinical stage 1

Asymptomatic No HIV related symptoms and no signs on examination. Not required

Persistent generalized Lymph nodes >1 cm, in two or more non­contiguous sites, in absence of Confirmed by histology
lymphadenopathy known cause and last more than 3 months

Clinical stage 2

Moderate weight loss Unexplained weight loss. No weight gained in pregnancy Confirmed by documented loss <10%
body weight

Recurrent upper respiratory Symptom complex, e.g. unilateral face pain with one­side nasal discharge Sub­clinical laboratory, where
tract infection (two or more in (sinusitis) or painful swollen eardrum (otitis media), cough with purulent available, e.g. culture of suitable body
past 6 months) sputum (bronchitis), sore throat (pharyngitis) without the characteristics of fluid.
viral infection (e.g. cough or running nose)

Herpes zoster Painful rash of small fluid filled blisters in distribution of a nerve supply but Clinical diagnosis
does not cross midline.

Angular cheilitis Splits or cracks on lips at the angle of the mouth, not due to iron or Clinical diagnosis
vitamin deficiency and usually responds to antifungal treatment.

Recurrent oral ulcerations Aphthous ulceration, typically with a halo of inflammation and a yellow­ Clinical diagnosis

 
146

 Diseases Clinical diagnosis Definitive diagnosis

(occurring 2 or more in past 6 grey pseudomembrane.

Months)

Papular pruritic eruptions Papular pruritic vesicular lesions, often with marked post­inflammatory Clinical diagnosis
hyperpigmentation

Seborrhoeic dermatitis Itchy oily skin condition, particularly affecting hairly areas (forehead, Clinical diagnosis
underarms, upper trunk and perineum)

Fungal nail infections Fungal paronychia (painful red and swollen nail bed) or onycholysis Culture of nail scrapings.
(separation of the nail from the nail bed) of the fingernails (white
discoloration – especially involving proximal part of nail plate – with
thickening and separation of nail from nail bed)

Clinical stage 3

Severe unexplained weight Unexplained weight loss (> 10% of body weight) without trying, and Documented loss of more than
loss (more than 10% noticeable thinning of face, waist and extremities or body mass index <
measured body weight) 18.5kg/m2). In pregnancy weight loss may be masked 10% of body weight.

Unexplained chronic Chronic diarrhoea (loose or watery stools 3 or more times daily) reported Not required but confirmed if three or
diarrhoea for longer than one for longer than one month. more stools observed and
month documented as unformed, and two or
more stool tests reveal no pathogens

Unexplained persistent fever Reports of fever or night sweats for more than one month, either Documented fever >37.5 °C
(intermittent or constant and intermittent or constant with reported lack of response to antibiotics or
antimalarials. No other obvious foci of disease reported or found on with negative blood culture,

 
147

 Diseases Clinical diagnosis Definitive diagnosis

for longer than one month) examination. Malaria must be excluded in malarial areas. negative Ziehl­Nielsen (ZN)

stain, negative malaria smear,

normal or unchanged chest X­ray

(CXR) and no other obvious

focus of disease.

Persistent oral candidiasis Persistent or recurring creamy­white curd­like plaques which can be Clinical diagnosis
scraped off (pseudomembranous), or red patches on tongue, palate or
lining of mouth, usually painful or tender (erythematous form)

Oral hairy leukoplakia Fine white, small, linear or corrugated lesions onlateral borders of the Clinical diagnosis
tongue, which do not scrape off

Pulmonary TB Chronic symptoms lasting for more than 2­3 weeks: cough, haemoptysis, Isolation of M.tuberculosison sputum
shortness of breath, chest pain, weight loss, fever, night sweats and culture or histology of lung biopsy
(current) fatigue (together with compatible symptoms)

PLUS

either positive or negative sputum smear

AND

compatible chest radiograph (including but not restricted to upper lobe

infiltrates, cavitation, pulmonary fibrosis and shrinkage). No evidence of
extrapulmonary disease

 
148

 Diseases Clinical diagnosis Definitive diagnosis

Severe bacterial Fever accompanied by specific symptoms or signs that localize infection, Isolation of bacteria from appropriate
and response to appropriate antibiotic. clinical specimens (i.e. usually sterile
infection (e.g. pneumonia, sites)
meningitis, empyema,

pyomyositis, bone or joint

infection, septicemia and

severe pelvic inflammatory
disease)

Acute necrotizing ulcerative Severe pain, ulcerated gingival papillae, loosening of teeth, spontaneous Clinical diagnosis
bleeding, bad odour, and rapid loss of bone and/or soft tissue.
gingivitis or necrotizing

ulcerative periodontitis

Unexplained anaemia No presumptive clinical diagnosis. Diagnosed on laboratory testing and

(<8g/dl), neutropenia (<5 not explained by other non­HIV
x109/l) or chronic (more than conditions. Not responding to standard
one month) therapy
thrombocytopenia (<5 x109/l)
for more than one month with haematinics, antimalarials or
anthelmintics as outlined in relevant
national treatment guidelines, WHO
IMCI guidelines or other relevant
guidelines.

 
149

 Diseases Clinical diagnosis Definitive diagnosis

Clinical stage 4

HIV wasting syndrome Unexplained involuntary weight loss (over 10% of body weight) with Documented weight loss (> 10% of
obvious wasting or body mass index below 18.5 body weight);

PLUS PLUS

unexplained chronic diarrhoea (loose or watery stools three or more times Two or more unformed stools negative
daily) reported for longer than one month for pathogens

OR OR

Reported of fever or night sweats for more than one month without other Documented temperature
cause and lack of response to antibiotics or antimalarials. Malaria must be
excluded in malarial areas. > 37.5 °C with no other cause of
disease, negative blood culture,
negative malaria slide and normal or
unchanged CXR

Pneumocystis pneumonia Dyspnoea on exertion or nonproductive cough of recent onset (within the Cytology or immunofluorescent
past three months), tachypnoea and fever; microscopy of induced sputum or
bronchoalveolar lavage
AND
(BAL), or histology of lung
Chest X­ray evidence of diffuse bilateral interstitial infiltrates;
tissue.
AND

No evidence of bacterial pneumonia, bilateral crepitations on auscultation

with or without reduced air entry

 
150

 Diseases Clinical diagnosis Definitive diagnosis

Recurrent bacterial Current episode plus one or more episodes in last six months. Acute Positive culture or antigen test of a
pneumonia (this episode plus onset (under two weeks) of symptoms (e.g. fever, cough, dypsnoea, and compatible organism
one or more episodes in last chest pain) PLUS new consolidation on clinical examination or chest x­
six months) ray, response to antibiotics

Chronic herpes simplex virus Painful, progressive anogenital or orolabial ulceration; lesions caused by Positive culture or DNA (by PCR) of
(HSV) infection (orolabial, recurrent HSV infection and reported for more than one month. History of HSV or compatible cytology/histology
genital or anorectal) of more previous episodes. Visceral HSV requires definitive diagnosis.

than one month, or visceral of

any duration

Oesophageal candidiasis Recent onset of retrosternal pain or difficulty in swallowing (food and Macroscopic appearance at
fluids) together with oral candidiasis endoscopy or bronchoscopy, or by
microscopy/ histopathology

Extrapulmonary TB (EPTB) Systemic illness (e.g. fever, night sweats, weakness and weight loss). M. tuberculosis isolation or compatible
Other evidence of extrapulmonary or disseminated TB varies by site: histology from appropriate site,
pleural, pericardial, peritoneal involvement, meningitis, mediastinal or together with compatible
abdominal lymphadenopathy, osteitis. symptoms/signs (if culture/histology is
from respiratory specimen then must
Discrete cervical lymph node M. tuberculosis infection is usually have other evidence of
considered a less severe form of EPTB extrapulmonary disease)

Kaposi’s sarcoma Typical appearance in skin or oropharynx of persistent, initially flat Macroscopic appearance at
patches with a pink or bloodbruise colour, skin lesions that usually endoscopy or bronchoscopy, or by
develop into violaceous plaques or nodules histopathology

 
151

 Diseases Clinical diagnosis Definitive diagnosis

Definitive diagnosis must be made on

histopathology

CMV disease (organ other Retinitis only: may be diagnosed by experienced clinicians. Typical eye Compatible histology or CMV
than liver, spleen or lymph lesions on fundoscopic examination: discrete patches of retinal whitening demonstrated in CSF
nodes) with distinct borders, spreading centrifugally, often following blood
vessels, associated with retinal vasculitis, haemorrhage and necrosis. by culture or DNA (by PCR)

CNS toxoplasmosis Recent onset of a focal neurological abnormality or reduced level of Positive serum Toxoplasma antibody
consciousness AND response within 10 days to specific therapy AND (if available) single/multiple
intracranial mass lesions on
neuroimaging (CT scan or MRI)

HIV encephalopathy Clinical finding of disabling cognitive and/or motor dysfunction interfering Diagnosis of exclusion: and (if
with activities of daily living, progressing over weeks or months in the available) neuroimaging
absence of a concurrent illness or condition other than HIV infection which
might explain the findings (CT scan or MRI).

Extrapulmonary Meningitis: usually subacute fever with increasingly severe headache, Isolation of Cryptococcus neoformans
Cryptococcosis (including meningism, confusion, behavioural changes that respond to cryptococcal from extrapulmonary site or positive
meningitis) therapy cryptococcal antigen test (CRAG) on
CSF/blood

Disseminated non­ No presumptive clinical diagnosis. Diagnosed by finding atypical

tuberculous mycobacterial species from stool,
blood, body fluid or other body tissue,

 
152

 Diseases Clinical diagnosis Definitive diagnosis

mycobacteria infection excluding lung

Progressive multifocal No presumptive clinical diagnosis. Progressive neurological disorder

leukoencephalopathy (PML) (cognitive dysfunction, gait/speech
disorder, visual loss, limb weakness
and cranial nerve palsies) together
with hypodensity white matter lesions
on neuroimaging or positive
polyomavirus (JCV) PCR on CSF

Cryptosporidiosis (with No presumptive clinical diagnosis. Identification of Cryptosporidia

diarrhoea lasting

for more than one month)

Chronic isosporiasis No presumptive clinical diagnosis. Identification of Isospora with multiple

stool examinations

Disseminated mycosis No presumptive clinical diagnosis. Histology, antigen detection or culture

(coccidioidomycosis, from clinical specimen or blood culture
histoplasmosis)

Recurrent non­typhoid No presumptive clinical diagnosis. Blood culture.

Salmonella bacteraemia

 
153

 Diseases Clinical diagnosis Definitive diagnosis

Lymphoma (cerebral or B cell No presumptive clinical diagnosis. Histology of relevant specimen or

non­Hodgkin) or other solid neuroimaging techniques for CNS
HIV associated tumours

tumours

Invasive cervical carcinoma No presumptive clinical diagnosis. Histology or cytology

Visceral leishmaniasis No presumptive clinical diagnosis. Diagnosed by histology (amastigotes

visualized) or culture from any
appropriate clinical specimen

HIV­associated nephropathy No presumptive clinical diagnosis. Renal biopsy

HIV­associated No presumptive clinical diagnosis. Cardiomegaly and evidence of poor

cardiomyopathy left ventricular function confirmed by
echocardiography

 
154

 Annex 2 ­ Clinical and definitive diagnosis criteria of HIV/AIDS­related diseases in children

The following criteria are used for the children less than 15 years with confirmed HIV infection

Diseases Clinical diagnosis Definitive diagnosis

CLINICAL STAGE 1

Asymptomatic No HIV­related symptoms and no clinical signs on examination Not required

Persistent generalized Swollen or enlarged lymph nodes >1 cm at two or more non­contiguous Clinical diagnosis

lymphadenopathy sites (excluding inguinal), without known cause

CLINICAL STAGE 2

Unexplained persistent Enlarged liver and spleen without obvious cause Clinical diagnosis

hepatosplenomegaly

Papular pruritic Papular pruritic vesicular lesions Clinical diagnosis

Eruptions

Fungal nail infections Fungal paronychia (painful, red and swollen nail bed) or onycholysis Clinical diagnosis
(painless

separation of the nail from the nail bed). Proximal white subungual
onchomycosis is uncommon without immunodeficiency

Angular cheilitis Splits or cracks at the angle of the mouth not attributable to iron or vitamin Clinical diagnosis

deficiency, and usually responding to antifungal treatment

 
155

 Diseases Clinical diagnosis Definitive diagnosis

Lineal gingival Erythematous band that follows the contour of the free gingival line; may Clinical diagnosis
be
Erythema
associated with spontaneous bleeding

Extensive wart virus infection Characteristic warty skin lesions; small fleshy grainy bumps, often rough, Clinical diagnosis
flat on

sole of feet (plantar warts); facial, more than 5% of body area or

disfiguring

Extensive molluscum Characteristic skin lesions: small fleshcoloured or pink, dome­shaped or Clinical diagnosis

contagiosum infection umbilicated growths may be inflamed or red; facial, more than 5% of body
area or disfiguring. Giant molluscum may indicate more advanced
immunodeficiency

Recurrent oral Current event plus at least one previous episode in past six months. Clinical diagnosis
Aphthous ulceration, typically with a halo of inflammation and yellow­grey
ulceration pseudomembrane

Unexplained persistent Asymptomatic bilateral swelling that may spontaneously resolve and Clinical diagnosis
recur, in
parotid enlargement
absence of other known cause, usually painless

Herpes zoster Painful rash with fluid­filled blisters, dermatomal distribution, can be Clinical diagnosis
haemorrhagic on erythematous background, and can become large and
 
156

 Diseases Clinical diagnosis Definitive diagnosis

confluent. Does not cross the midline

Recurrent or chronic upper Current event with at least one episode in past 6 months. Symptom Clinical diagnosis
complex;
respiratory tract infection
fever with unilateral face pain and nasal discharge (sinusitis) or painful
swollen

eardrum (otitis media), sore throat with productive cough (bronchitis), sore

throat (pharyngitis) and barking crouplike cough (LTB). Persistent or

recurrent

ear discharge

CLINICAL STAGE 3

Unexplained moderate Weight loss: low weight­for­age, up to −2 standard deviations from Documented failure to gain weight or
weight loss: body weight of –2 SD,
mlnutrition or wasting the mean, not explained by poor or inadequate feeding and or other failure to gain weight on standard
infections,
management and no other cause
and not adequately responding to standard management identified during investigation

Unexplained persistent Unexplained persistent (14 days or more) diarrhoea (loose or watery Stools observed and documented as
diarrhoea stool, three unformed. Culture and microscopy
reveal no pathogens
or more times daily), not responding to standard treatment

 
157

 Diseases Clinical diagnosis Definitive diagnosis

Unexplained persistent fever Fever or night sweats for longer than one month, either intermittent or Documented fever of >37.5ºC with
constant, not responding to antibiotics or antimalarials. No other obvious negative blood culture, negative
(intermittent or foci of disease reported or found on examination. Malaria must be malaria smear and normal or
constant, for longer than one excluded in malarious areas unchanged CXR, and no other
month) obvious foci of disease

Persistent oral candidiasis Persistent or recurring creamy white to yellow soft small plaques which Microscopy or culture
can be
(after first 8 weeks of life)
scraped off (pseudomembranous), or red patches on tongue, palate or
lining

of mouth, usually painful or tender (erythematous form)

Oral hairy leukoplakia Fine small linear patches on lateral borders of tongue, generally Clinical diagnosis
bilaterally,

which do not scrape off

Acute necrotizing ulcerative Severe pain, ulcerated gingival papillae, loosening of teeth, spontaneous Clinical diagnosis
gingivitis or stomatitis, or bleeding, bad odour, and rapid loss of bone and/or soft tissue

acute necrotizing ulcerative

periodontitis

Lymph node TB Non­acute, painless “cold” enlargement of peripheral lymph nodes, Histology or fine needle aspirate
localized to positive for Ziehl–Neelsen stain or

 
158

 Diseases Clinical diagnosis Definitive diagnosis

One region. Response to standard anti­TB treatment in one month culture

Pulmonary TB Nonspecific symptoms, such as chronic cough, fever, night sweats, One or more sputum smear positive
anorexia and for acid­fast bacilli and/or
radiographic
weight loss. In the older child also productive cough and haemoptysis.
History of contact with adult with smear­positive PTB. No response to abnormalities consistent with active
standard broad TB and/or culture positive for
Mycobacterium tuberculosis
spectrum­antibiotic treatment

Severe recurrent bacterial Cough with fast breathing, chest in drawing, nasal flaring, wheezing, and Confirmed by isolation of bacteria
pneumonia grunting. Crackles or consolidation on auscultation. Responds to course from appropriate clinical specimens
of antibiotics. Current episode plus one or more in previous 6 months (induced

sputum, BAL, lung aspirate)

Symptomatic lymphocytic CXR: bilateral reticulonodular

interstitial pulmonary infiltrates
interstitial pneumonitis No presumptive clinical diagnosis present for more than two months
with no response to antibiotic
treatment and

no other pathogen found. Oxygen

saturation persistently <90%. May
present with cor pulmonale and may
have increased exercise­induced
fatigue.

 
159

 Diseases Clinical diagnosis Definitive diagnosis

Characteristic histology

Chronic HIV­associated History of cough productive of copious amounts of purulent sputum CXR may show honeycomb
(bronchiectasis only), with or without clubbing, halitosis, and crepitations appearance (small cysts) and/or
lung disease (including and/or persistent areas of opacification
bronchiectasis) and/or widespread lung
wheezes on auscultation
destruction, with fibrosis and loss of
volume

Unexplained anaemia No presumptive clinical diagnosis Laboratory testing not explained by

other non­HIV conditions, not
(<8 g/dl), neutropenia responding to standard therapy with
(< 109/l) or chronic haematinics, antimalarials or
thrombocytopenia anthelmintics as outlined in

(<50 x10 9/ l) WHO IMCI guidelines

CLINICAL STAGE 4

Unexplained a severe wasting, Persistent weight loss, stunting or wasting not explained by poor or Documented weight loss for age of
stunting or severe malnutrition inadequate feeding, other infections and not adequately responding in more than – 3SD from the mean with
not adequately responding to two weeks to standard therapy. Visible severe wasting of muscles, with or without oedema
or without oedema of both feet, and/or weight­for­height of – 3SD, as
standard therapy defined by WHO IMCI guidelines

 
160

 Diseases Clinical diagnosis Definitive diagnosis

Pneumocystis pneumonia Dry cough, progressive difficulty in breathing, cyanosis, tachypnoea Cytology or immunofluorescent
and fever; chest indrawing or stridor. (Severe or very severe microscopy of induced sputum or
(PCP) pneumonia as in IMCI.) Usually of rapid onset especially in infants bronchoalveolar lavage, or histology
under six months of age. Response to high­dose co­trimoxazole of lung tissue

with/without prednisolone. CXR typical bilateral perihilar diffuse

infiltrates

Recurrent bacterial infection, Fever accompanied by specific symptoms or signs that localize Culture of appropriate clinical
e.g. empyema, pyomyositis, infection. Responds to antibiotics. Current episode plus one or more in specimen
bone or joint infection, previous 6 months
meningitis but excluding
pneumonia

Chronic herpes simplex Severe and progressive painful orolabial, genital, or anorectal lesions Culture and/or histology
caused by HSV infection present for more than one month
infection (orolabial or

cutaneous of more than

1 month’s duration or

visceral at any site)

Oesophageal candidiasis Difficulty in swallowing, or pain on swallowing (food and fluids). In Macroscopic appearance at
young children, suspect particularly if oral candida observed and food endoscopy, microscopy of specimen
(or candidiasis of trachea, refusal occurs and/or difficulties/crying when feeding from tissue or

 
161

 Diseases Clinical diagnosis Definitive diagnosis

bronchi or lungs) macroscopic appearance at

bronchoscopy or histology

Disseminated/Extrapulmonary Systemic illness usually with prolonged fever, night sweats, weight loss. Positive microscopy showing acid­
TB Clinical features depend on organs involved, such as sterile pyuria, fast bacilli or culture of M.
pericarditis, ascitis, pleural effusion, meningitis, arthritis or orchitis. tuberculosis from blood or other
Responde to standard anti­TB treatment relevant specimen except

sputum or BAL. Biopy and histology

Kaposi sarcoma Typical appearance in skin or oropharynx of persistent, initially Not required but may be confirmed
flat, patches with a pink or blood­bruise colour, skin lesions that by:
usually develop into nodules
• typical redpurple lesions seen on
bronchoscopy or endoscopy;

• dense masses in lymph nodes,

viscera or lungs by palpation or
radiology;

• histology

CMV retinitis or CMV Retinitis only Definitive diagnosis required for

infection affecting another other sites. Histology. CSF
CMV retinitis may be diagnosed by experienced clinicians:
polymerase chain reaction (PCR)
organ, with onset at age typical eye lesions on serial fundoscopic examination; discrete
 
162

over 1 month patches of retinal whitening with distinct borders, spreading

centrifugally,

often following blood vessels, associated with retinal vasculitis,

haemorrhage and necrosis

Central nervous system Fever, headache, focal neurological system signs and Computed tomography (CT) scan (or
toxoplasmosis onset convulsions. Usually responds within 10 days to specific other neuroimaging) showing
therapy single/multiple lesions with mass
after age 1 month
effect/enhancing with contrast

Extrapulmonary Meningitis: usually subacute, fever with increasing severe CSF microscopy (India ink or Gram
cryptococcosis including headache, meningism, confusion, behavioural changes that stain), serum or CSF cryptococcal
respond to cryptococcal therapy antigen test or culture
meningitis

HIV encephalopathy At least one of the following, progressing over at least two Neuroimaging demonstrating atrophy
months in the absence of another illness: and basal ganglia calcification and
excluding other causes
• failure to attain, or loss of, developmental milestones, loss of
intellectual ability; or

• progressive impaired brain growth demonstrated by

 
163

 stagnation of head circumference; or

• acquired symmetrical motor deficit accompanied by two or

more of the following: paresis, pathological reflexes, ataxia,
gait disturbances

Disseminated mycosis No presumptive clinical diagnosis Histology: usually granuloma

formation
(histoplasmosis,
coccidioidomycosis, or Isolation: antigen detection from
affected tissue; culture or
penicilliosis)
microscopy from clinical specimen or
blood culture

Disseminated No presumptive clinical diagnosis Nonspecific clinical symptoms

nontuberculous including progressive weight loss,
fever, anaemia, night sweats, fatigue
mycobacterial
or diarrhoea;
Infection
plus culture of atypical mycobacteria

species from stool, blood, body fluid

or other body tissue, excluding lung

Chronic cryptosporidiosis No presumptive clinical diagnosis Cysts identified on modified ZN

microscopic examination of
unformed stool

 
164

Chronic isosporiasis No presumptive clinical diagnosis Identification of Isospora

Cerebral or B cell non­ No presumptive clinical diagnosis Diagnosed by central nervous

system neuroimaging, histology of
Hodgkin lymphoma
relevant specimen

Progressive multifocal No presumptive clinical diagnosis Progressive neurological disorder

(cognitive dysfunction, gait/speech
leukoencephalopathy
disorder, visual loss, limb weakness
and

cranial nerve palsies) together with

hypodense white matter lesions on
neuroimaging or positive
polyomavirus JC (JCV) PCR on CSF

Symptomatic HIV­ No presumptive clinical diagnosis Renal biopsy

associated

Nephropathy

Symptomatic HIV­ No presumptive clinical diagnosis Cardiomegaly and evidence of poor

associated left ventricular function confirmed by

Cardiomyopathy echocardiography

 
165

 Annex 3 ­ Summary of ARV drugs

�

Drug name Abbreviation Dosage Tablet/Day Interactionswithfood Side effects

Nucleoside Reverse Transcripatase Inhibitors (NRTIs) Nucleotide Reverse Transcriptase Inhibitors (NtRTIs)
Zidovudine AZT, 300 mg, twice daily 2 No interaction Leukopenia, anemia, fatigue, malaise,
ZDV headache
nausea, vomiting, hepatitis, myopathy actic
acidosis with hepatic steatosis

Stavudine d4T 30 mg, twice daily 2 No interaction Peripheral neuropathy

Nausea, vomiting, elevated liver enzymes

Lactic acidosis with hepatic steatosis

Didanosine ddI < 60kg: 125 mg, twice daily 4 Take 30 – 60 minutes Peripheral neuropathy, headache
before meals
≥ 60kg: 250 mg, twice daily Pancreatitis, nausea, diarrhea, abdominal pain

Rash, fever; lactic acidosis with hepatic

steatosis
Lamivudine 3TC 150 mg twice daily or 300mg 2 No interaction Minimal toxicity
once daily
Headache, insomnia; rash; lactic acidosis with
hepatic steatosis
Abacavir ABC 300 mg twice daily 2 No interaction; alcohol Hypersensitivity reaction (fever, rash, nausea,
increases ABC levels vomiting, abdominal pain ­­ can be fatal on
41% rechallenge)

Lactic acidosis with hepatic steatosis

Tenofovir TDF 300 mg once daily 1 No interaction Nausea, vomiting, diarrhea
Non­Nucleoside Reverse Transcripatase Inhibitors (NNRTIs)

 
166

Efavirenz EFV 600 mg at bed time 1 Avoid taking after high Rash, Stevens­Johnson syndrome
fat meals
CNS symptoms, including insomnia, nightmares,
hallucinations, mood disturbance

Elevated liver enzymes

Teratogenic. Contraindicated in pregnancy.

Nevirapine NVP 200 mg once daily in the first 2 No interaction Rash, Stevens­Johnson syndrom
2 weeks, then 200 mg twice
daily Elevated liver enzymes
Protease Inhibitors (PIs)
Atanazavir ATV/r 300 mg /100 mg, once daily 1 Gastrointestinal intolerance, nausea, vomiting,
+ ritonavir diarrhea, abdominal pain,, elevated bilirubin,
elevated liver enzymes
Lopinavir + LPV/r LPV/r: 133,3 mg/33 mg twice 3 tablets each time, twice daily GI intolerance, nausea, vomiting, diarrhea
ritonavir daily (400 mg/100 mg twice daily
4 tablet each time, twice daily Rash; headache; hyperglycemia, fat redistribution
when used with EFV or NVP and abnormal lipids
LPV/r: 200 mg/50 mg For the patients who have never
been on ARV
2 tablets/twice daily, even if taken
with EFV or NVP (400/100 mg
twice daily)
For the ARV patient
3 tablets twice daily, even if taken
with EFV or NVP (600/150 mg
twice daily)
Ritonavi RTV Mostly used to boost other GI intolerance, nausea, vomiting, diarrhea
PIs
Altered taste; Hepatitis; Hyperglycemia, fat
redistribution and abnormal lipids

 
167

 Annex 4 ­ Pediatric ARV dosages – Standardized with Developmental Indexes of Vietnamese Children

NRTIs

Weight (kg) Stavudine2 Zidovudine Lamivudine Didanosine3 Abacavir4

Surface
area1 (m2) (d4T, Zerit) (ZDV, Retrovir) (3TC, Epivir) (ddI, Videx) (ABC, Ziagen)

1 mg/kg 180­240mg/m2 x 4 mg/kg x <3 months: 50 mg/m2 x 2 times/day 8 mg/kg x

x 2 times/day 2 times/day 2 times/day 3 months ­13 years: 90­120 mg/m2x 2 2 times/day

times/day

≥13 years or > 60kg: 200 mg x 2

times/day

Syrup Capsule Syrup Tablet Syrup Tablet Syrup Tablet Syrup Tablet
1mg/ml 15,20,30m 10mg/ml 150mg
g 100, 300mg 10mg/ml 10mg/ml 25, 50,100mg 20mg/ml 300mg

3,5–4,9kg 5ml 5ml 2ml 3ml 2ml

0,21–
0,28m2

5,0–6,5kg 6ml 6ml 3ml 4ml 2.5ml

0,28–
0,33m2

6,6–8,0kg 8ml 8ml 3ml 5ml 2 tablets of 25mg 3ml

0,34–
0,40m2

 
168

8,1–10,0kg 8­9kg: 8­8,9kg: 9ml 1 tablet of 4ml 2 tablets of 25mg 4ml

0,40– 9ml 100mg
0,47m2
9­10kg:
10ml 9­10kg: 10ml

10,1– 1 capsule 1 tablet of 5ml 2 tablets of 25mg 5ml

11,9kg of 15mg 100mg
0,48–
0,54m2

12,0– 1 capsule 12­13,9 kg: 1 6ml (1 tablet of 50mg + 1 tablet of 6ml

14,9kg of 15mg tablet of 100mg 25mg)
0,55–
0,64m2 14­14,9 kg:

½ tablet of
300mg

15,0– 1 capsule ½ tablet of 7ml ½ tablet 2 tablets of 50mg morning ½ tablet

16,9kg of 20mg 300mg
0,65– 1 tablet of 50mg + 1 tablet of
0,72m2 25mg night

17,0– 1 capsule ½ tablet of 8ml ½ tablet 2 tablets of 50mg ½ tablet

19,9kg of 20mg 300mg
0,72–
0,83m2

20,0– 1 capsule 2 tablets of 1 tablet 20­22kg:2 tablets of 50mg 20­23 kg:½

24,9kg of 20mg 100mg morning tablet
0,83– 22­24,9kg: (1 tablet of
½ tablet 23,1­24,9 kg:1

 
169

0,98m2 night 100mg+1 tablet of 25mg) tablet morning,

½ tablet night

25,0– 1 capsule 2 tablets of 1 tablet (1 tablet of 100mg+1 tablet of 1 tablet morning

29,9kg of 30mg 100mg 25mg) x2 times/day
0,99– ½ tablet night
1,15m2

≥ 30,0kg 1 capsule 1 tablet of 1 tablet 30­60kg: (1 tablet of 1 tablet

of 30mg 300mg 100mg+1 tablet of 25mg)
≥1,15m2
>60kg: 2 tablets of 100mg

NNRTIs
�

Nevirapine5 (NVP, Viramune) Efavirenz6 (EFV, Sustiva, Stocrin)

Weight (kg)
Initial dose – once daily for 14 days Maintenance dose – 2 times/day
Surface area (m2)
160­200 mg/ m2 <8 years: 200 mg/ m2 Once daily at bedtime

≥8 years: 160­200 mg/ m2

Syrup Tablet Syrup Tablet Capsule

10 mg/ml 200 mg 10 mg/ml 200 mg 50, 200, 600 mg

3,5 – 4,9 kg 5 ml 5 ml

0,21 – 0,28 m2

 
170

5,0 – 6,5 kg 6 ml 6 ml Do not use for children < 3 years

0,28 – 0,33 m2

6,6 – 8,0 kg 7.5 ml 7.5 ml and

0,34 – 0,40 m2

8,1 – 10,0 kg 9 ml 9 ml Weight < 10 kg

0,40 – 0,47 m2

10,1 – 11,9 kg 10 ml ½ tablet ½ tablet 1 capsule of 200 mg once daily

0,48 – 0,54 m2

12,0 – 14,9 kg ½ tablet ½ tablet 1 capsule of 200 mg once daily

0,55 – 0,64 m2

15,0 – 16,9 kg ½ tablet 1 tablet morning (1 capsule of 200mg + 1 capsule of 50mg) once daily

0,65 – 0,72 m2 ½ tablet night

17,0 – 19,9 kg 1 tablet 1 tablet morning (1 capsule of 200mg + 1 capsule of 50mg) once daily

0,72 – 0,83 m2 ½ tablet night

20,0 – 24,9 kg 1 tablet 1 tablet morning (1 capsule of 200mg + 2 capsules of 50mg) once daily

0,83 – 0,98 m2 ½ tablet night

25,0 – 29,9 kg 1 tablet 1 tablet (1 capsule of 200mg + 3 capsules of 50 mg) once daily

0,99 – 1,15 m2

 
171

 ≥ 30,0 kg 1 tablet 1 tablet 30 – 39.9kg: 2 capsules of 200 mg once daily

≥ 1,15m2 ≥ 40.0 kg: 3 capsules of 200mg or 1 capsule of 600mg

once daily

PIs
�

Lopinavir/Ritonavir7 Trimethoprim/ sulfamethoxazole (TMP + SMX)

Weight (kg) (LPV/RTV, Kaletra, Aluvia) Cotrimoxazole (CTX)

Surface area (m2) 5­7.9 kg: 16 mg/kg x 2 times/day

8­9.9 kg: 14 mg/kg x 2 times/day TMP 5 mg /kg once daily

10­13.9 kg: 12 mg/kg x 2 times/day

14­39.9 kg: 10 mg/kg x 2 times/day

Syrup Coated tablet Aluvia Coated tablet Aluvia Syrup TMP 8 mg/SMX 40 mg/ Tablet
ml
(LPV 80mg/ RTV (LPV 100 mg/RTV 25 (LPV 200 mg/ RTV 50 mg) TMP 80 mg/ SMX 400 mg (single
20 m /ml) mg) (TMP 40 mg/ SMX 200ml/ 5 strength)
ml)

3,5 – 4,9 kg 1 ml 2.5ml once daily

0,21 – 0,28 m2

5,0 – 6,5 kg 1 ml 4 ml once daily

0,28 – 0,33 m2

 
172

6,6 – 8,0 kg 1.5 ml 5 ml once daily ½ tablet once daily

0,34 – 0,40 m2

8,1 – 10,0 kg 1.5 ml 1 tablet 6 ml once daily ½ tablet once daily

0,40 – 0,47 m2

10,1 – 11,9 kg 2 ml 2 tablets morning 7 ml once daily ½ tablet once daily

0,48 – 0,54 m2 1 tablet night

12,0 – 14,9 kg 2 ml 2 tablets 1 tablet 8 ml once daily 1 tablet once daily

0,55 – 0,64 m2

15,0 – 16,9 kg 2 ml 2 tablets 1 tablet 10 ml once daily 1 tablet once daily

0,65 – 0,72 m2

17,0 – 19,9 kg 2.5 ml 2 tablets 1 tablet 11 ml once daily 1 tablet once daily

(0,72 – 0,83 m2

20,0 – 24,9 kg 3 ml 2 tablets 1 tablet 1 ½ tablets once daily

0,83 – 0,98 m2

25,0 – 29,9 kg 3.5 ml 3 tablets 2 tablets morning 2 tablets once daily

0,99 – 1,15 m2 1 tablet night

≥ 30,0 kg 4 tablets 2 tablets 2 tablets once daily

≥ 1,15m2

 
173

 Fixed dose combination (FDC)

�

Use single ARVs for initial dose x 14 initial days Use fixed dose combinations (FDCs)8

Weight (kg) for maintenance dose x 2 times/day

Surface area d4T: 1 mg/kg 3TC: 4 mg/kg NVP: 160­20 Fixed dose combination d4T­6 Fixed dose combination Fixed dose
(m2) mg/m2 d4T­12 (Tablet d4T 12 combination d4T­30
(Syrup 1 mg /ml, (Syrup 10 mg / ml, (Tablet d4T 6 mg/ 3TC 30 mg/ mg/ 3TC 60 mg/ NVP 100
Capsule 15, 20, 30 (Syrup 10 mg / ml, NVP 50 mg) mg) (Tablet
mg) Tablet 150 mg)
Tablet 200 mg) d4T 30 mg/ 3TC 150
mg/ NVP 200 mg)
(Triomune Baby)
2 times/day (Fixed dose
2 times/day (Triomune Junior) combination for
Once daily adults)

3,5 – 4,9 kg 5 ml 2 ml 5 ml once daily Do not use fixed dose combinations (FDCs) for children < 5kg

0,21 – 0,28 (use single drugs)

m2

5,0 – 6,5 kg 6 ml 3 ml 6 ml once daily 5 – 5.9 kg: 1 tablet 6.0 – 6.5 kg:

0,28 – 0,33 1½ tablets morning, 1 tablet night

m2

6,6 – 8,0 kg 8 ml 3 ml 7.5 ml once daily 1½ tablets

0,34 – 0,40

 
174

m2

8,1 – 10,0 kg 8­8.9kg: 9 ml 9 ml once daily 1½ tablets

0,40 – 0,47 9­10kg: 10 ml 4 ml

m2

10,1 – 11,9 1 capsule of 15mg 5 ml ½ tablet once daily 2 tablets 1 tablet

kg

0,48 – 0,54
m2

12,0 – 14,9 1 capsule of 15 mg 6 ml ½ tablet once daily 2 tablets 1 tablet

kg

0,55 – 0,64
m2

15,0 – 16,9 1 capsule of 20 mg 7 ml or ½ tablet ½ tablet once daily 1½ tablets morning, 1

kg tablet night

0,65 – 0,72
m2

17,0 – 19,9 1 capsule of 20 mg 8 ml or ½ tablet 1 tablet once daily 1½ tablets morning, 1

kg tablet night

0,72 – 0,83
m2

20,0 – 24,9 1 capsule of 20 mg 1 tablet morning, ½ 1 tablet once daily 1½ tablets

kg tablet night

 
175

0,83 – 0,98
m2

25,0 – 29,9 1 capsule of 30 mg 1 tablet 1 tablet once daily 2 tablets

kg

0,99 – 1,15
m2

≥ 30,0 kg 1 capsule of 30 mg 1 tablet 1 tablet once daily 1 tablet

≥ 1,15m2

 
176

 Annex 5 ­ Interactions of ARVs

�

ARV drugs Interacted drugs Mechanism/effect Recommendations

LPV/r Clarithromycin Decreased metabolism, clarithromycin Adjust clarithromycin dose only in renal
concentration increased failure

EFV, NVP Clarithromycin Increased metabolism, clarithromycin The efficacy of MAC treatment and
concentration decreased prophylaxis may be decreased

EFV Rifabutin Increased metabolism, significant decrease Increase rifabutin dose to 450­600mg daily
in rifabutin levels/ Efavirenz level may or 600mg twice weekly.
decrease
No dosage change necessary for efavirenz.

NVP Itraconazole Can affect concentration of both NVP and Adjust dose of NVP and intraconazole
itraconazole

EFV Intraconazole Decrease 35­44% maximum & minimum Adjust dose of intraconazole
concentration of intraconazole and
intraconazole­OH

ddI Gancyclovir ddI level increased up to 100% Monitor for ddI­related adverse reactions.

LPV/r Ketoconazole Decreased metabolism, ketoconazole Use with caution at ketoconazole doses > 200
concentration increased mg/day

ddI Fluoroquinolone Mark decrease in quinolone drug levels Administer didanosine at least 2 hours after
antibiotics because of cationization quinolone.

 
177

RTV, LPV/r, Rifabutin Decreased metabolism, significant increase Decrease rifabutin to 150mg every other day
in rifabutin levels/ Increased metabolism, or 3 time per week. Consider increasing
saquinavir level may decrease indinavir to 1000mg every 8 hours if this is
the only PI administered; No dosage change
for other PIs.

NVP, LPV/r Rifampicin Increased metabolism, significant decrease

in NVP and PI levels

EFV, RTV, NVP Rifampicin Increased metabolism, decrease in PI or Possible combination use.
nevirapine levels

d4T, NVP, EFV, RTV, Methadone Decreased methadone concentration Withdrawal syndrome can occur; may
LPV require increase in methadone dose

ATV Contraceptives Increased concentration of contraceptives No need to adjust doses of contraceptives

Norethindrone,
Ethinyl estradiol

NVP, RTV, LPV Ethyl estradiol Significant decrease in Ethyl estradiol Use alternative or supportive contraception
concentration methods

ddI TDF Increased ddI levels Decrease ddI dose to 250mg a day

 
178

Annex 6 ­ Severity grading of ARV side effects in adults

�

Parameters GRADE 1 GRADE 2 GRADE 3 GRADE 4

(Mild) (Moderate) (Severe) (Life­
Mild Activity of Significant threatening)
symptoms, patients may limitation in Severe
no limitation be limited and patient's limitation in
of patients in need support, activity; patient's
action, no no treatment or medication activity,
treatment/ limited treatment is significant
intervention treatment is required, support
is required required hospitalization needed,
might be intensive
needed treatment is
required,
hospitalization
or palliative
care
HAEMATOLOGY GRADE 1 GRADE 2 GRADE 3 GRADE 4
Haemoglobin 8.0 − 9.4 g/dl 7.0 − 7.9 g/dl 6.5 − 6.9 g/dl <6.5 g/dl OR

Absolute neutrophil 1000 −1500/ 750 − 999/ 500 − 749/ <500/mm3

count mm3 OR 1.0 mm3 OR 0.75 mm3 OR 0.5 OR <0.5/G/l*

− 1.5/G/l* − 0.99/G/l* − 0.749/G/l*

Platelets 75000 − 50000 − 20000 − <20000/mm3

99000/mm3 74999/mm3 49999/mm3 OR <20/G/l*

OR 75 − 99/ OR 50 − OR 20 −

G/l* 74.9/G/l* 49.9/G/l*

CHEMISTRIES GRADE 1 GRADE 2 GRADE 3 GRADE 4
SODIUM
Hyponatraemia 130 − 135 123 − 129 116 − 122 <116 meq/l

meq/l OR meq/l OR meq/l OR OR <116

130 − 135 123 − 129 116 − 122 mmol/l

mmol/l mmol/l mmol/l

Hypernatraemia 146 − 150 151 − 157 158 − 165 >165 meq/l

meq/l OR meq/l OR meq/l OR OR >165

146 − 150 151 − 157 158 − 165 mmol/l

mmol/l mmol/l mmol/l

POTASSIUM

 
179

Hyperkalaemia 5.6 − 6.0 6.1 − 6.5 6.6 − 7.0 >7.0 meq/l

meq/l OR meq/l OR 6.1 meq/l OR 6.6 OR >7.0

5.6
− 6.5 mmol/l − 7.0 mmol/l mmol/l
− 6.0 mmol/l
Hypokalaemia 3.0 − 3.4 2.5 − 2.9 2.0 − 2.4 <2.0 meq/l

meq/l OR meq/l OR 2.5 meq/l OR 2.0 OR <2.0

3.0
− 2.9 mmol/l − 2.4 mmol/l mmol/l
− 3.4 mmol/l
BILIRUBIN
Hyperbilirubinaemia >1.0 − 1.5 x >1.5 − 2.5 x >2.5 − 5 x >5 x ULN

ULN ULN ULN

GLUCOSE
Hypoglycaemia 55 − 64 mg/ 40 − 54 mg/ 30 − 39 mg/ <30 mg/dl

dl OR 3.01 − dl OR 2.19 − dl OR 1.67 − OR <1.67

3.55 mmol/l 3.00 mmol/l 2.18 mmol/l mmol/l

Hyperglycaemia 116 − 160 161 − 250 mg/ 251 − 500 mg/ >500 mg/dl

(nonfasting and no mg/dl OR dl OR 8.91 − dl OR 13.89 − OR >27.76

6.44
prior diabetes) 13.88 mmol/l 27.76 mmol/l mmol/l
− 8.90
mmol/l
Triglycerides 200 – 399 400 − 750 751 − 1200 >1200 mg/dl

mg/dl OR mg/dl OR mg/dl OR OR

2.25 ­ 4.51 4.52 − 8.47 8.48 − 13.55 >13.55

mmol/l mmol/l mmol/l mmol/l

Creatinine >1.0 − 1.5 x >1.5 − 3.0 x >3.0 − 6.0 x >6.0 x ULN

ULN ULN ULN

Liver enzymes
AST (SGOT) 1.25 − 2.5 x >2.5 − 5.0 x >5.0 − 10.0 >10.0 x ULN

ULN ULN x ULN

ALT (SGPT) 1.25 − 2.5 x >2.5 − 5.0 x >5.0 − 10.0 >10.0 x ULN

ULN ULN x ULN

GGT 1.25 − 2.5 x >2.5 − 5.0 x >5.0 − 10.0 >10.0 x ULN

ULN ULN x ULN

Alkaline 1.25 − 2.5 x >2.5 − 5.0 x >5.0 − 10.0 >10.0 x ULN

phosphatase ULN ULN x ULN

PANCREATIC ENZYMES

 
180

Amylase >1.0 − 1.5 x >1.5 − 2.0 x >2.0 − 5.0 x >5.0 x ULN

ULN ULN ULN

Pancreatic >1.0 − 1.5 x >1.5 − 2.0 x >2.0 − 5.0 x >5.0 x ULN

amylase ULN ULN ULN

Lipase >1.0 − 1.5 x >1.5 − 2.0 x >2.0 − 5.0 x >5.0 x ULN

ULN ULN ULN

Lactate <2.0 x ULN >2.0 x ULN Increased Increased

without without lactate with lactate with pH

acidosis acidosis pH <7.3 <7.3 with life

threatening
without life
threatening consequences

consequences
GASTROINTESTINAL GRADE 1 GRADE 2 GRADE 3 GRADE 4
Nausea Mild OR Moderate Severe Hospitalization

transient; discomfort discomfort required

reasonable OR intake OR minimal

intake decreased for intake for >3

maintained <3 days days

Vomiting Mild OR Moderate OR Severe Hypotensive

transient; persistent; vomiting of all shock OR

2−3 episodes 4−5 episodes foods/fluids in hospitalization

per day OR per day OR 24 hours OR for

mild vomiting vomiting orthostatic intravenous

lasting <1 lasting >1 hypotension Rx required

week week OR

intravenous

Rx required
Diarrhoea Mild OR Moderate OR Bloody Hypotensive

transient; persistent; diarrhoea OR shock OR

3−4 loose 5−7 loose orthostatic hospitalization

stools per stools per day hypotension required

 
181

 day OR mild OR diarrhoea OR >7 loose

diarrhoea lasting >1 stools/day OR

lasting <1 week intravenous

week Rx required
RESPIRATORY GRADE 1 GRADE 2 GRADE 3 GRADE 4
Dyspnoea Dyspnoea on Dyspnoea Dyspnoea at Dyspnoea

exertion with normal rest requiring O2

activity therapy
URINALYSIS GRADE 1 GRADE 2 GRADE 3 GRADE 4
Proteinuria
Spot urine 1+ 2+ or 3+ 4+ Nephrotic

syndrome
24­hour urine 200 mg to 1 g 1 g to 2 g 2 g to 3.5 g Nephrotic

loss/day OR loss/day OR loss/day OR syndrome OR

<0.3% OR 0.3% to 1.0% >1.0% OR >3.5 g loss/

<3 g/l OR 3 g to 10 >10 g/l day

g/l
Gross haematuria Microscopic Gross, no Gross plus Obstructive

only clots clots

MISCELLANEOUS GRADE 1 GRADE 2 GRADE 3 GRADE 4
Fever (oral, >12 37.7 − 38.5oC 38.6 − 39.5oC 39.6 − 40.5oC >40.5oC

hours) for >12

continuous

hours
Headache Mild; no Rx Moderate OR Severe OR Intractable

required non­narcotic responds to

analgesia Rx initial narcotic

Rx
Allergy Itching, no Limited rash Diffuse Anaphylactic
rash maculopapular shock
rash, phu mao
mach

Rash Erythema, Diffuse Vesiculation ANY ONE

hypersesnitivity pruritus maculopapular OR moist OF: mucous

 
182

 rash OR dry desquamation membrane

desquamation OR ulceration involvement,

suspected

Stevens­

Johnson

(TEN),

erythema

multiforme,

exfoliative

dermatitis
Fatigue Normal Normal Normal activity Unable to

activity activity reduced by care for self

reduced by reduced by >50%; cannot

<25% 25−50% work

 
183

 Annex 7 ­ Severity grading of ARV side effects in children

�

SEVERE,
POTENTIALLY
PARAMETER MILD MODERATE SEVERE
LIFE­
THREATENING

GENERAL GUIDANCE TO ESTIMATE GRADE OF SEVERITY a

Characterization Symptoms Symptoms Symptoms Symptoms causing

causing
of symptoms causing causing inability to perform
no or minimal greater inability
and general basic self­care
interference than minimal to perform functionsc:
guidance on with
interference usual social Requires medical or
management usual social
and with usual and functional operative
social intervention
functional activities:
activitiesb: and functional to prevent
Requires permanent
No therapy activities:
medical care impairment,
needed, May require
minimal and possible persistent disability
monitor
intervention Hospitalization or death

and monitoring

HAEMATOLOGY Standard International Units are listed in italics

Absolute 750 – 500 – 749/mm3 250 – 500/mm3 <250/mm3

neutrophil <1.000/mm3 0.5 x109 – 0.25 x109 – <0.250x109/L
0.75 x109 – 0.749x109/L 0.5x109/L
count <1x109/L

  184

Haemoglobin 8.5 – 10.0 7.5 ­ <8.5 g/dL 6.5 – <7.5 g/dL < 6.5 g/dL
g/dL 1.16 – <1.32 1.01 – <1.16 < 1.01 mmol/L
(child >60 days 1.32 – 1.55 mmol/L mmol/L
mmol/L or severe clinical
of age)
symptoms due to

anaemia (e.g.
cardiac

failure) refractory to

supportive therapy

Platelets 100.000­ 50.000­ 25.000­ <25.000/mm3

<125.000/mm3 <100.000/mm3 <50.000/mm3
100x109 – 50x109 – 25x109 – < 25x109/L
125x109/L <100x109/L <50x109/L or bleeding

GASTROINTESTINAL

Laboratory

ALT (SGPT) 1,25 – 2,5 x 2,6 – 5,0 x 5,1 – 10,0 x > 10,0 x ULN
ULN ULN ULN

AST (SGOT) 1,25 – 2,5 x 2,6 – 5,0 x 5,1 – 10,0 x > 10,0 x ULN
ULN ULN ULN

Bilirubin (>2 1,1 – 1,5 x 1,6 – 2,5 x 2,6 – 5,0 x > 5,0 x ULN
ULN ULN ULN
weeks of age)

Lipase 1,1 – 1,5 x 1,6 – 3,0 x 3,1 – 5,0 x > 5,0 x ULN
ULN ULN ULN

Pancreatic 1,1 – 1,5 x 1,6 – 2,0 x 2,1 – 5,0 x > 5,0 x ULN
amylase ULN ULN ULN

Clinical

  185

Diarrhoea

≥1 year of age Transient or Persistent Grossly bloody Life­threatening

intermittent episodes
diarrhoea OR consequences (e.g.
episodes of of unformed to
increase of ≥7 hypotensive shock)
unformed watery stools
stools OR OR stools per day
increase of ≤3 or
stools over increase of 4–
6 i.v. fluid
baseline per replacement
day stools over
Indicated Liquid stools
baseline resulting

Liquid stools per day in severe

<1 year of age Liquid stools dehydration
(more Liquid stools
unformed than with with moderate with aggressive
increased rehydration
usual) but Dehydration
usual number indicated OR

number per of stools per hypotensive shock

day day

OR mild
dehydration

Nausea Transient (<24 Persistent Persistent Persistent nausea

nausea nausea
hours) or with no or minimal
intermittent resulting in resulting in
minimal oral intake resulting
nausea with decreased oral
oral intake in dehydration and
no or minimal intake for 24–
48 for >48 hours aggressive
interference OR rehydration
with Hours
aggressive Indicated (e.g. i.v.
oral intake rehydration fluids)

indicated

(e.g. i.v. fluids)

  186

Pancreatitis Symptomatic Symptomatic Life­threatening

AND
NA AND consequences (e.g.
hospitalization hospitalization
circulatory failure,
not indicated not indicated
(other haemorrhage,
(other than
emergency than sepsis)
emergency
Treatment)
treatment)

Vomiting Transient or Frequent Persistent Life­threatening

intermittent episodes vomiting
consequences (e.g.
vomiting of vomiting resulting
hypotensive shock)
with no or with no or mild in orthostatic
minimal
dehydration hypotension
interference OR
with
aggressive
oral intake rehydration

indicated

(e.g. i.v. fluids)

ALLERGIC/DERMATOLOGICAL

Acute systemic Localized Localized Generalized Acute anaphylaxis

urticaria urticaria
allergic reaction urticaria OR OR life­threatening
(wheals) with indication
lasting for a angioedema bronchospasm or
few hours for medical
intervention with indication laryngeal oedema

OR mild for medical

angioedema intervention
OR

symptomatic

mild
bronchospasm

  187

Cutaneous Localized Diffuse Diffuse Extensive or

macular, macular,
reaction – rash macular rash generalized bullous
maculopapular, maculopapular,
or lesions OR
or morbilliform Stevens–
morbilliform
rash rash Johnson syndrome

OR target with vesicles or OR ulceration of

lesions limited number mucous membrane

of bullae OR involving two

superficial or more distinct

ulcerations of mucosal sites OR

mucous toxic epidermal

membrane
necrolysis (TEN)
limited to one
site

NEUROLOGICAL

Alteration in Alteration Alteration Alteration Behaviour

causing causing potentially
personality, causing
no or minimal greater than inability harmful to
behaviour or in minimal
interference to perform self or others or
moodb interference
with usual usual social life­threatening
social with usual
social and functional consequences
and functional
and functional activitiesb AND
activitiesb
activitiesb intervention

Indicated

  188

Altered mental Altered mental Mild lethargy Onset of Onset of delirium,

staus causing confusion,
status or somnolence obtundation or
no or minimal memory
causing coma
interference greater impairment,

with usual than minimal lethargy, or

social
interference somnolence
and functional
with usual causing
b
activities social inability

and functional to perform

activitiesb usual social

and functional

activitiesb

Neuromuscular Asymptomatic Muscle Muscle Disabling muscle

with weakness weakness
weakness weakness causing
decreased causing causing
(including strength greater inability to perform
inability
myopathy and on than minimal basic self­care
examination to perform functions
neuropathy) interference
OR usual social OR respiratory
with usual
mild muscle and functional muscle weakness
weakness social

and functional activitiesb impairing ventilation

causing no or

minimal activitiesb
interference

with usual
social

and functional

activitiesb

  189

Neurosensory Asymptomatic Sensory Sensory Disabling sensory

with alteration
alteration alteration or alteration or
(including sensory or paraesthesia
alteration paraesthesia paraesthesia
painful causing
on causing causing
neuropathy) examination greater inability inability to perform
OR to perform basic self­care
than minimal
minimal usual social functions c
paraesthesia interference

with usual and functional

causing no or
social Activities
minimal
interference and functional

with usual Activities

social and

functional
activities

OTHER LABORATORY PARAMETERS Standard International Units are listed in

italics

Cholesterol 170 ­ < 200 200 – 300 > 300 mg/dL NA

mg/dL mg/dL > 7,77 mmol/L
(fasting, 4,40 – 5,15 5,16 – 7,77
paediatric mmol/L mmol/L
<18 years old)

Glucose, serum, 116 – < 161 161 – < 251 251 – 500 > 500 mg/dL
mg/dL mg/dL mg/dL > 27,75 mmol/L
high: non­ 6,44 – < 8,89 8,89 – < 13,89 13,89 – 27,75
fasting mmol/L mmol/L mmol/L

Glucose, serum, 110 – < 126 126 – < 251 251 – 500 > 500 mg/dL
mg/dL mg/dL mg/dL > 27,75 mmol/L
high: fasting 6,11 – < 6,95 6,95 – < 13,89 13,89 – 27,75
mmol/L mmol/L mmol/L

  190

Lactate <2.0 x ULN ≥ 2.0 x ULN Increased Increased lactate

without without lactate with pH with pH <7.3

acidosis acidosis
<7.3 without with life­threatening

life­threatening consequences

consequences (e.g. neurological

or related findings, coma) or

condition
Present related condition
present

Triglycerides NA 500 – < 751 751 – 1.200 > 1.200 mg/dL

mg/dL mg/dL > 13,56 mmol/L
(fasting) 5,65 – < 8,49 8,49 – 13,56
mmol/L mmol/L

Notes:

a. Values are provided for children in general except where age groups are specifically
noted.

b. Usual social and functional activities in young children include those that are culturally­
and

Age appropriate (e.g. social interactions, play activities, learning tasks, etc.).

c. Activities that are culturally­ and age­appropriate (e.g. feeding self with culturally
appropriate

eating implement, walking or using hands)

  191

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