1 Pediatric HIV Infection HAIVN Harvard Medical School AIDS Initiative in Vietnam

2 Learning Objectives By the end of this session, participants should be able to: Explain how to diagnose children with HIV Describe WHO clinical staging for children Explain when and how to initiate cotrimoxazole prophylaxis in children List the 6 vaccines that are contraindicated in children with AIDS

3 Overview of Pediatric HIV >90% of global pediatric HIV due to mother-to-child transmission (MTCT) During pregnancy During delivery Most common time for infection After delivery Breastfeeding increases transmission risk by 5-20%

4 Overview of MTCT What is the risk of transmission without intervention? The overall MTCT rate is approximately 25-40% without intervention However, with current prophylactic strategies, the risk of transmission can be reduced to less than 2%

5 Pregnancy 5-10% Delivery 10-15% Breastfeeding 5-20% When Does MTCT Occur? In an untreated breastfeeding population, the total transmission rate is 25-40%

6 Management of HIV-Exposed Infants and Children Make diagnosis as soon as possible Give appropriate vaccines and prophylaxis Start antiretroviral therapy when indicated (for HIV-infected infants) Recognize and treat opportunistic infections Support growth and development

7 Diagnosis of HIV Infection: > 18 Months Confirmed by the same HIV antibody test used for adults HIV infection is diagnosed when the serum gives 3 positive results in 3 tests with 3 different bioproducts Only laboratories certified by MoH are authorized to confirm HIV positive test results before reporting the result to patients Guidelines for the Diagnosis and Treatment of HIV/AIDS. Ministry of Health, 2009.

8 Diagnosis of HIV Infection: < 18 months (1) Because an infant up to 18 months of age may carry maternal HIV antibodies, regular HIV antibody test will be positive whether baby has HIV or not Test will either be detecting baby’s antibodies or mother’s This leads to difficulties interpreting an HIV antibody positive test result in children < 18 months

9 Diagnosis of HIV Infection: < 18 months (2) Diagnosis is based on PCR for viral DNA or RNA < 9 months: 2 positive PCR (performed after 4-6 weeks of life) 9 to 18 months: if HIV antibody test is positive then need PCR to confirm ( as for < 9 month old) If breastfeeding, stop for 6-8 weeks before testing Guidelines for the Diagnosis and Treatment of HIV/AIDS. Ministry of Health, 2009.

MOH 2009 HIV exposed children (<9 months old) PCR testing PCR testing not available PCR positive PCR negative No HIV infection Breastfed within 6 weeks of PCR test? Repeat PCR 6 weeks after last breastfeeding Continued Care at HIV outpatient clinic 2nd PCR HIV infection confirmed HIV antibody test at 18 months NO YES POS NEG POS NEG HIV Diagnosis for HIV Exposed Children <9 months

Antibody testing Antibody testing (+) Antibody testing(-) Antibody testing (-) PCRtesting PCR testing (as < 9 months old) HIV exposed children (9-18 months old) MOH 2009 NoHIV infection No HIV infection HIV Diagnosis for HIV Exposed Children 9-18 months old

12 Clinical Diagnosis of Severe HIV/AIDS Disease in < 18 months Stage 4 clinical disease PCP Toxoplasmosis Cryptococcus Wasting syndrome Esophageal candidiasis EPTB (excluding axillary LN – BCG disease) At least 2 of the 3 findings: Oral thrush (if > 1 month of age) Severe bacterial pneumonia Severe sepsis HIV Antibody test positive, plus: OR

13 Staging of Pediatric HIV Infection

14 WHO Pediatric Clinical Staging Clinical staging should be performed for infants and children with confirmed HIV infection If HIV infection cannot be confirmed in infants <18 months, a presumptive diagnosis may be made in those with severe disease Accurate staging is important for deciding when to start ART

15 WHO Pediatric Stages (1) Stage 1 Child is asymptomatic May have persistent generalized lymphadenopathy Stage 2 Characterized by: Hepatosplenomegaly Recurrent or chronic upper respiratory tract infections Papular pruritic eruption Herpes zoster

Linear gingival erythema Stage 2 Diseases (1) Zona

PPE: lower arms and legs, leaves scarring after resolution Stage 2 Diseases (2)

Bilateral parotid enlargement Stage 2 Diseases (3)

19 WHO Pediatric Stages (2) Stage 3 Characterized by: Unexplained moderate malnutrition Unexplained diarrhea >14 days Unexplained fever for >1 month Pulmonary, lymph node TB Stage 4 Characterized by: Unexplained severe wasting/malnutrition PCP Recurrent severe bacterial infection Extrapulmonary TB HIV encephalopathy

Oral hairy leukoplakia: Side of tongue, can’t scrape off Stage 3 Diseases (1) Oral candidiasis

Stage 3 Diseases (2) Pulmonary TB TB Lymphadenitis

22 Lymphocytic interstitial pneumonitis: Typical nodular infiltrates in mid and lower lungs Stage 3 Diseases (3)

Stage 4 Diseases (1) Herpes Simplex chronic infection (>1 month)

Penicillium Marneffei skin lesions: Flesh-color, umbilicated papules concentrating mainly on face Stage 4 Diseases (2)

Quiz: Which stage? ScenariosStage ? A 5 year old boy who has: had an unexplained fever for over a month now and also has a skin rash consistent with papular pruritic eruption (PPE) A 1 year old girl who has TB meningitis A 7 year old boy who with generalized lymphadenopathy but otherwise appears well with no other symptoms 3 4 1

26 Immunological Staging (1) The degree of immunosuppression in HIV infected children is assessed by the percentage (%) of CD4 cells CD4 percentage is used for children under 5 years of age, whereas CD4 number is used for children 5 years and older

27 Immunological Staging (2) <11 months months months ≥ 5 yrs Not significant > 35%> 30%> 25%> 500 cells Mild30 – 35% 25 – 30% 20 – 25% 350−49 9 cells Advanced25 – 29% 20−24 % 15−20%200−34 9 cells Severe<25% <1500 cells <20% <750 cells <15% <350 cells <15% <200 cells

28 Overview on Care and Treatment of Children with HIV/AIDS

29 Cotrimoxazole Prophylaxis for HIV- Exposed and -Infected Children HIV-exposed children Confirmed HIV-infected children Start 4–6 weeks after birth Continue until exclusion of HIV infection < 24 months 24 – 60 months> 60 months All Clinical stages 2, 3 and 4 regardless of CD4 count or CD4 < 25% or ≤ 750 cells/mm 3 regardless of clinical stage Clinical stage 3 or 4 regardless of CD4 count or CD4 ≤ 350 regardless of clinical stage

30 Immunization Children with HIV and C.S 4 should not be given live vaccines VaccineHIV-exposed infants, before diagnosis is known HIV + with clinical stages I, II, III HIV + with clinical stage IV Nationally-supported vaccines BCGAs scheduledDO NOT GIVE DPTAs scheduled Poliomyelitis oral As scheduled IM vaccine only Hepatitis BAs scheduled MeaslesAs scheduled DO NOT GIVE JEAs scheduled Optional vaccines HIBAs scheduled VaricellaAs scheduled DO NOT GIVE MumpsAs scheduled DO NOT GIVE RubellaAs scheduled DO NOT GIVE

31 ARV Indications Children with confirmed HIV infection : AgeStarting ART < 24 months Start ART as soon as possible (regardless of clinical stage or CD4) months Clinical stage 3 or 4 regardless of CD4 count CD4% ≤ 25% or CD4 ≤ 750 cells/mm3 regardless of clinical stage > 60 monthsIndications as per HIV-infected adults

32 Common Opportunistic Infections in HIV-infected Children

33 Pneumocystis carinii Pneumonia (PCP) Most common OI in young children Interstitial, diffuse pneumonia Characterized by: Fever Cough Progressive dyspnea Tachypnea Hypoxia Peaks at 2-8 months of age Infant mortality after treatment up to 40%

34 AIDS-Defining Conditions by Age at Diagnosis for Perinatally-Acquired AIDS Cases Reported through 1999, United States Age in Months Number of Cases Other AIDS-defining conditions Pneumocystis jiroveci pneumonia

35 Tuberculosis Diagnosis of TB in children in VN High index of suspicion needed Suspect in any child with prolonged cough, low grade fevers, failure to thrive BK smear, PPD (tuberculin skin test), CXR Gastric aspirates used in small infants Look for LN, peripheral and mediastinal FNA to evaluate for lymph node infection Differential Diagnosis: Lymphoid interstitial pneumonia, PCP, bacterial pneumonia

36 Support for Growth and Development Growth High rates of growth failure due to decreased intake and/or increased nutrient demands Give multivitamins containing Vitamin A Treat iron-deficiency anemia Maximize caloric intake Development Watch for spastic limbs and gait, encephalopathy, other neurological deficits Review developmental milestones Delay or loss of developmental milestones indicate HIV encephalopathy

37 Key Points Most children get HIV through mother- to child transmission Children > 18 months are tested with antibody test Younger children may still carry mother’s antibodies, need different testing strategy Use clinical and immunological staging to determine ART eligibility Important to look closely at child’s growth and development markers for clues about health

38 Thank you! Questions?