Optimizing Pediatric HIV-1 Treatment in Infants With Prophylactic Exposure to Nevirapine, Nairobi, Kenya

Summary

Globally, children who acquire HIV-1 increasingly do so in the context of maternal antiretroviral prophylaxis. It is important to determine whether maternal antiretroviral prophylaxis should alter infant treatment regimens. Nevirapine (NVP) is commonly used for PMTCT and is also a commonly used first-line drug for treatment of pediatric HIV-1. Approximately half of infants exposed to NVP have detectable NVP resistance early in infancy, with loss of detectable resistance over time. Thus, if an HIV-1 infected child was exposed to single-dose NVP prophylaxis, the question remains whether NVP or any NNRTI can be used effectively in therapeutic regimens. Alternative PI-based regimens are associated with heat-lability, poor palatability, cumulative toxicity, and fewer salvage options. This poses challenges for pediatric PI-based highly active antiretroviral therapy (HAART) in settings without refrigeration and limited antiretroviral repertoire. It is plausible that in older NVP-exposed infants (older than 6 months since exposure) who are genotypically NVP-susceptible, that nevirapine will be effective and useful.

We propose to study resistance in a pediatric HIV-1 clinical trial involving 100 children. Among children enrolled at between 6 and 18 months of age, we will provide real-time field-based genotypic NVP-resistance testing, and randomize 100 NVP-susceptible children to NVP-containing versus NVP-sparing HAART to compare therapeutic response, adverse events, and morbidity in the 2 arms during 2-year follow-up. Follow-up in these studies will be closely monitored by an external Data Safety and Monitoring Board (DSMB).

Conditions

• HIV Infections

Interventions

DRUG

AZT/3TC/NVP (zidovudine/lamivudine/nevirapine)

First line regimen

DRUG

d4T/3TC/NVP (stavudine/lamivudine/nevirapine)

First line regimen

DRUG

AZT/3TC/ABC (zidovudine/lamivudine/abacavir)

First line regimen

DRUG

d4T/3TC/ABC (stavudine/lamivudine/abacavir)

First line regimen For children who have anaemia(Hb of\<8g/dl), AZT will be substituted for d4T.

DRUG

ddI/ABC/LPV/r (didanosine/abacavir/lopinavir-ritonavir)

Second line regimen

DRUG

ABC/ ddI or TDF / NVP or EFV (abacavir / didanosine or tenofovir / nevirapine or efavirenz)

Second line regimen - Among children randomized to NVP sparing HAART, who will be initiated on a regimen containing lopinavir/ritonavir, zidovudine and lamivudine will be substituted with abacavir and didanosine or tenofovir (TDF) and lopinavir/ ritonavir will be replaced with nevirapine or efavirenz (EFV) in case of treatment failure of the LPV/r containing regimen.

DRUG

ABC/3TC/NVP (abacavir/lamivudine/nevirapine)

First line regimen

Sponsors & Collaborators

• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

  collaborator NIH

• University of Washington

  lead OTHER

Principal Investigators

• Grace C John-Stewart, MD, PhD · University of Washington

• Dalton Wamalwa, MMed, MPH · Department of Paediatrics and Child Health, Kenyatta National Hospital, University of Nairobi

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

6 Months

Max Age

18 Months

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2007-09-30

Primary Completion

2009-05-31

Completion

2009-12-31

FDA Drug

Yes

Countries

• Kenya

Study Locations