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Optimizing Pediatric HIV-1 Treatment in Infants With Prophylactic Exposure to Nevirapine, Nairobi, Kenya (6-12 Month RCT)
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).
Details
| Lead sponsor | University of Washington |
|---|---|
| Phase | Phase 3 |
| Status | TERMINATED |
| Enrolment | 34 |
| Start date | 2007-09 |
| Completion | 2009-12 |
Conditions
- HIV Infections
Interventions
- AZT/3TC/NVP (zidovudine/lamivudine/nevirapine)
- d4T/3TC/NVP (stavudine/lamivudine/nevirapine)
- AZT/3TC/ABC (zidovudine/lamivudine/abacavir)
- d4T/3TC/ABC (stavudine/lamivudine/abacavir)
- ddI/ABC/LPV/r (didanosine/abacavir/lopinavir-ritonavir)
- ABC/ ddI or TDF / NVP or EFV (abacavir / didanosine or tenofovir / nevirapine or efavirenz)
- ABC/3TC/NVP (abacavir/lamivudine/nevirapine)
Primary outcomes
- Incidence of Mortality — 2 years
Death during follow-up - Immunologic Failure — 2 years
Immunologic treatment failure was defined as CD4% dropping below 15%, after a previous result greater than or equal to 15% (following along WHO Guidelines). - Viral Failure — 2 years
Virologic treatment failure was defined as follow-up (at least 24 weeks after enrollment date) viral load \> 400 copies.
Countries
Kenya