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Antiretroviral Therapy in HIV-infected Children

HAIVNHarvard Medical School AIDS

Initiative in Vietnam

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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

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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

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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 monthsChild is infected with

HIV

If infant is breastfeeding, repeat PCR after infant has stopped breastfeeding for 6 weeks

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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

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Cotrimoxazole Preventive Therapy

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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

All Clinical stages 2, 3 and 4 regardless of CD4 count orCD4 < 25% or ≤ 750 cells/mm3 regardless of clinical stage

Clinical stage 3 or 4 regardless of CD4 count or CD4 ≤ 350 regardless of clinical stage

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Cotrimoxazole Prophylaxis (2)

Discontinuation:

Alternative therapy: • If allergic to cotrimoxazole, use dapsone

2mg/kg/day once a day (100mg pill)

ART/no ART ActionIf not on ART lifelong therapy

If on ART discontinue when:• CD4 > 25% for 1-5 year-olds• CD4 > 350 for > 5 year-olds

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Indications for the Initiation of

ARV Therapy

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Classification of Immunodeficiency

Level of Immuno-deficienc

y

CD4% or cells/mm3

≤11 months

12–35 months

36 –59 months

≥ 5 years

None >35 % >30 % >25 %> 500

cells/mm3

Mild 30-35 % 25-30 % 20-25 %350 – 499 cells/mm3

Moderate 25-29 % 20-24 % 15-19 %200 – 349 cells/mm3

Severe<25 %<1500

cells/mm3

<20 %<750

cells/mm3

<15 %<350

cells/mm3

<15%<200

cells/mm3

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Criteria for ART Initiation

Age Starting ART

< 24 monthsStart ART as soon as possible

(regardless of clinical stage or CD4)

24 - 60 months

Clinical stage 3 or 4 regardless of CD4 count

CD4% ≤ 25% or CD4 ≤ 750 cells/mm3 regardless of clinical stage

> 60 months Indications as per HIV-infected adults

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First-line ARV Regimens

Age Starting ART

< 24 monthsNNRTI exposed: AZT + 3TC + LPV/r

NNRTI un-exposed: AZT + 3TC + NVP

24 - 36 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

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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

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ARV Dosing

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ARV Dosing for Children

BSA (m2) = √ 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

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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

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Zidovudine (AZT)

Zidovudine (AZT)

Suspension 10mg/ml

Tablet 100, 300mg

180-240 mg/m2

twice daily

Max 300 mg/dose twice

daily

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Nevirapine (NVP)

Nevirapine (NVP)Suspension 10mg/ml, Tablet 200mg

Lead-in Dose 160-200 mg/m2 daily x 14 days

Maintenance Dose

< 8 years: 200 mg/m2 twice daily

≥ 8 years: 160-200 mg twice daily

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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

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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

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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

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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

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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

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Laboratory Monitoring

TestsBaseline (at ART

initiation)

Follow-up

At 4 weeksAt 6

monthsAt 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

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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

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D4T-Based Regimen: Weight 6 kg

Weightd4T

Syrup 1 mg/ml

3TCSyrup 10

mg/ml

NVPSyrup

10 mg/ml5.0 – 6.5 kg 6 ml twice a day 3 ml twice a day 6 ml once a day

Initial 14 days: Lead-in dose, Use individual drugs

Then, change to FDC:

WeightFDC d4T-6:

d4T 6mg, 3TC 30mg, NVP 50 mg Triomune Baby

6.0 – 6.5 kg 1½ tablets in morning and 1 tablet at night

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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

WeightAZT

Tablet 300 mg

3TCTablet 150 mg

orSyrup 10 mg/ml

NVPTablet 200 mg

17.0 - 19.9 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:

WeightFDC AZT-60:

AZT 60mg, 3TC 30mg, NVP 50mg14.0 - 19.9

kg2½ tablets twice per day

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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

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AZT and EFV - Based Regimen: Weight 22 kg

WeightAZT

Tablet 100 mg

3TCTablet 150 mg

EFVCapsule 50mg, 200

mg

20.0 - 24.9 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)

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Adherence Techniques for Children

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Adherence for Missed Doses

Clarify the history with the caretaker

Suggest solutions

Follow up Adherence

3 Steps to Address “Missed Doses”

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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 ?

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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

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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

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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

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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

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Thank you!

Questions?