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

• Status: Terminated
• Trial end date: 2009-12-01
• Target enrollment: 0
• Participant gender: All

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
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University of Washington
• Collaborator: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
• Treatments: Abacavir; Didanosine; Dideoxynucleosides; Efavirenz; Lamivudine; Lopinavir; Nevirapine; Ritonavir; Stavudine; Tenofovir; Zidovudine

Criteria

Inclusion Criteria:

• 6-18 months age

• HIV-1 DNA detection with confirmation (positive on two HIV-1 DNA filter paper tests)

• Mother exposed to NVP-containing PMTCT regimen during currently ended pregnancy and/or infant received NVP-containing PMTCT regimen

• Infant susceptible to NVP (i.e. no detectable NVP resistance on genotypic testing)

• Caregiver of infant plans to reside in Nairobi for at least 3 years

• Caregiver is able to provide sufficient location information

Exclusion Criteria:

• Infant has received any prior antiretroviral therapy (expect prophylaxis for PMTCT)

• Infant has evidence of active tuberculosis

• Mother currently receiving NVP-containing HAART and breastfeeding the infant