This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. PACTG P1021 is a Phase I/II open label study which will evaluate the long-term safety and antiviral activity of a once-daily triple combination regimen (FTC, EFV, and ddI) in HIV-1 infected pediatric subjects (90 days to 21 years of age) who are nanve to antiretroviral therapy (<56 days perinatal prophylaxis, <7 days of cumulative antiretroviral treatment) and have screening plasma HIV-1 RNA levels >5000copies/mL. The study will enroll 36 to 42 evaluable HIV-1 infected pediatric subjects who will receive treatment for a minimum of 48 wks. Subjects will be stratified based on their age at entry; at least 6 subjects will be enrolled per age group (90 days to <3 years of age; 3 to 12 years of age; and 13 to 21 years of age) to allow adequate pharmacokinetic data to be collected in each age group. PACTG P1021 will characterize the disposition of FTC, will determine the PK data for ddI-EC QD, and compare the bioavailability of the enteric coated formulation with the ddI pediatric powder for oral solution. Intensive PK studies at Week 2 of treatment will be used to determine if dose adjustments of the initial doses of one, two, or all three study medications are needed. Dose adjustments will be implemented at the subject's next study visit. P1021 will evaluate the association between virologic and immunologic responses and PK levels, adherence measures, genotypes of cytochrome P4503A drug metabolizing enzymes, recent thymic emigrants, and HIV RNA determinants. Detailed studies of immunologic function changes during therapy will be performed. The HIV resistance mutation profile of each subject will be correlated with virologic, pharmacologic and immunologic response markers in order to evaluate the role of resistance in virologic failure.
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