1 Antiretroviral Therapy in HIV-infected Children HAIVN Harvard Medical School AIDS Initiative in Vietnam

2 Learning Objectives By the end of this session, participants should be able to: Outline criteria for starting an HIV+ child on ARVs Identify first line ARV regimens for children in Vietnam Describe how to prepare ARV doses for children based on age, weight, and BSA Propose recommendations to improve ARV adherence in children

3 Diagnosis of HIV Infection in Infants and Children The earlier the better! Early diagnosis, and early ART, greatly reduce mortality All PLWHA with children should be encouraged to test their children for HIV Diagnostic protocol is divided into 3 age groups: 0-18 months 9-18 months > 18months

4 Flow Chart for PCR Testing in Infants < 9 Months First PCR at 4-6 weeks of age Second PCR as soon as possible ELISA at 18 months Child is infected with HIV If infant is breastfeeding, repeat PCR after infant has stopped breastfeeding for 6 weeks – – + +

5 Diagnosing Children 9 to 18 Months and > 18 Months For children 9-18 months: Perform ELISA first If positive, perform PCR as for children under 9 months If negative, repeat ELISA at 18 months If breastfeeding, stop for 6 weeks before ELISA testing. If ELISA positive, perform PCR For children >= 18 months: Perform ELISA

6 Cotrimoxazole Preventive Therapy

7 Cotrimoxazole Prophylaxis (1) 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 AllClinical 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

8 Cotrimoxazole Prophylaxis (2) Discontinuation: Alternative therapy: If allergic to cotrimoxazole, use dapsone 2mg/kg/day once a day (100mg pill) ART/no ARTAction If not on ARTlifelong therapy If on ARTdiscontinue when: CD4 > 25% for 1-5 year-olds CD4 > 350 for > 5 year-olds

9 Indications for the Initiation of ARV Therapy

10 Classification of Immunodeficiency Level of Immuno- deficiency CD4% or cells/mm 3 ≤11 months 12–35 months 36 –59 months ≥ 5 years None>35 %>30 %>25 % > 500 cells/mm 3 Mild30-35 %25-30 %20-25 % 350 – 499 cells/mm 3 Moderate25-29 %20-24 %15-19 % 200 – 349 cells/mm 3 Severe <25 % <1500 cells/mm 3 <20 % <750 cells/mm 3 <15 % <350 cells/mm 3 <15% <200 cells/mm 3

11 Criteria for ART Initiation 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

12 First-line ARV Regimens AgeStarting ART < 24 months NNRTI exposed: AZT + 3TC + LPV/r NNRTI un-exposed: AZT + 3TC + NVP months AZT + 3TC + NVP > 36 months AZT + 3TC + NVP/EFV In case of intolerance to AZT, change to ABC. If there is contraindication of ABC, use d4T

13 ARV Regimens Co-administered with TB Drugs Children >3 years old and > 10kg Children < 3 years old and < 10kg AZT + 3TC + EFV or AZT+ 3TC + ABC AZT + 3TC + NVP or AZT+ 3TC + ABC Rifampicin lowers NVP levels; it’s preferable to use EFV when possible

14 ARV Dosing

15 ARV Dosing for Children BSA (m 2 ) = √ Weight (kg) x Height (cm)/3600 Two common ways: Weight-band dosing Body Surface Area (BSA) * Weight and height should be recorded at every visit

16 Stavudine and Lamivudine Lamivudine (3TC) Suspension 10mg/ml Tablet 150mg 4 mg/kg twice daily Max 150mg twice daily Stavudine (Zerit, D4T) Suspension 1mg/ml Tablet 15, 20, 30mg 1 mg/kg twice daily Max 30 mg twice daily

17 Zidovudine (AZT) Suspension 10mg/ml Tablet 100, 300mg mg/m2 twice daily Max 300 mg/dose twice daily

18 Nevirapine (NVP) Suspension 10mg/ml, Tablet 200mg Lead-in Dose mg/m2 daily x 14 days Maintenance Dose < 8 years: 200 mg/m2 twice daily ≥ 8 years: mg twice daily

19 Efavirenz (EFV) Use EFV in children > 3 years & weight ≥ 10kg 10 – 15 kg 200 mg once daily 15 – 20 kg 250 mg once daily 20 – 25 kg 300 mg once daily 25 – 33 kg 350 mg once daily 33 – 40 kg 400 mg once daily > 40 kg 600 mg once daily

20 D4T Fixed Dose Combinations (FDC) d4T-FDCs twice daily d4T-6: tablet d4T 6mg/ 3TC 30mg/ NVP 50mg (Triomune Baby) used for children < 15kg d4T-12: tablet d4T 12mg/ 3TC 60mg/ NVP 100mg (Triomune Junior) used for children < 30mg and > 12kg d4T-30: tablet d4T 30mg/ 3TC 150mg/ NVP 200mg used for children ≥ 30mg

21 AZT Fixed Dose Combination (FDC) AZT-FDCs twice daily AZT-60: tablet (AZT 60mg, 3TC 30mg, NVP 50mg) used for children< 25kg AZT-300: tablet (AZT 300mg, 3TC 150mg, NVP 200mg) used for children≥ 25kg

22 Preparing ARVs for Children Syringes that can be snugly connected to the bottles can be used to draw up the exact amount of medication needed. Use syringe to measure drugs. Do not use cups

23 Pediatric ARV Monitoring Clinical Physical growth, nutritional status - use growth chart Development – neurologic, cognitive, social, psychological Social Support for caretakers Evaluate adherence to PCP prophylaxis and/or ARV

24 Laboratory Monitoring Tests Baseline (at ART initiation) Follow-up At 4 weeks At 6 months At 12 months Every 6 months thereafter CD4, CD4% CBC, ALT CBC if use AZT ALT if use NVP Pregnancy test for adolescent girls If suspected Viral load If available

25 Case Study 1 19-month-old HIV positive child is eligible for ART His weight is 6 kg Write a correct prescription for this child using a d4T-based regimen

26 D4T-Based Regimen: Weight 6 kg Weight d4T Syrup 1 mg/ml 3TC Syrup 10 mg/ml NVP Syrup 10 mg/ml 5.0 – 6.5 kg6 ml twice a day3 ml twice a day6 ml once a day Initial 14 days: Lead-in dose, Use individual drugs Then, change to FDC: Weight FDC d4T-6: d4T 6mg, 3TC 30mg, NVP 50 mg Triomune Baby 6.0 – 6.5 kg1½ tablets in morning and 1 tablet at night

27 Case Study 2 4 year old HIV positive child is eligible for ART His weight is 18 kg Write a correct prescription for this child using a AZT-based regimen

AZT-Based Regimen: Weight 18 kg Weight AZT Tablet 300 mg 3TC Tablet 150 mg or Syrup 10 mg/ml NVP Tablet 200 mg kg ½ tablet twice per day ½ tablet twice a day or 8 ml syrup twice a day 1 tablet once per day Initial 14 days: Lead-in dose, Use individual drugs Then, change to FDC: Weight FDC AZT-60: AZT 60mg, 3TC 30mg, NVP 50mg kg 2½ tablets twice per day

29 Case Study 3 6 year old HIV positive child, weight 22 kg Has pulmonary TB and is on TB treatment Write a correct prescription for this child using a AZT-based regimen

30 AZT and EFV - Based Regimen: Weight 22 kg Weight AZT Tablet 100 mg 3TC Tablet 150 mg EFV Capsule 50mg, 200 mg kg 2 tablet twice per day 1 tablet in morning, ½ tablet in evening 1 capsule of 200mg and 2 capsules of 50mg once per day Use EFV for patients on TB therapy (> 3 years old and ≥ 10 kg)

31 Adherence Techniques for Children

32 Adherence for Missed Doses Clarify the history with the caretaker Suggest solutions Follow up Adherence 3 Steps to Address “Missed Doses”

33 Missed Doses: Clarify the History with Caretaker Question to clarify: WHAT medicine(s) were missed ? HOW many dose(s) were missed ? WHEN were the dose(s) missed ? WHO was responsible to deliver the medicines ? WHY did the caretaker think it happened ?

34 Missed Doses: Suggested Solutions (1) Hard to take medicines: Complaint/ Problem Suggested Solution Tastes terrible give with food, fruit jam or honey substitute crushed pills for suspension Hard to swallow pills/capsules crush pills GI side effects combine with food consider taking anti-nausea medicine

35 Missed Doses: Suggested Solutions (2) Ways for caretaker to remember to give the medicine to the child: Pick an event that is easy to link the medicine to Give family a pill-box for tablets, when appropriate Suggest they use an alarm clock for alerting when taking the medicines

36 Missed Doses: Follow up Adherence Schedule a time for counseling staff to check adherence with the family and make plans for ongoing adherence support by: Phone calls Clinic visits Home-care visits

37 Key Points ARVs can be initiated in a child with a confirmed HIV infection Preferred first line regimen in children is same as in adults: AZT/3TC/NVP All medications in children are dosed according to child’s age and weight Good pediatric adherence requires a team approach

38 Thank you! Questions?