Optimizing Pediatric HIV-1 Treatment in Infants With Prophylactic Exposure to Nevirapine, Nairobi, Kenya
Status:
Terminated
Trial end date:
2009-12-01
Target enrollment:
Participant gender:
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).
Phase:
Phase 3
Details
Lead Sponsor:
University of Washington
Collaborator:
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)