PACTG P1021: EMTRICITABINE IN COMBINATION WITH EFAVIRENZ & DIDANOSINE IN ART

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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. Primary: 1) To determine the long-term safety and tolerance of a regime of FTC + EFV + ddI administered once daily in HIV-infected pediatric subjects who are nanve, or have very limited exposure, to anti-HIV therapy. 2) To determine the antiviral activity of a regimen of FTC + EFV + ddI administered once daily in treatment of nanve, or very limited antiretroviral exposed, pediatric subjects. Secondary: 1) To determine the steady state pharmacokinetic (PK) parameters for FTC in a pediatric population and examine potential age related differences in the disposition of FTC. 2) To obtain PK data for ddI following once daily administration of the enteric coated formulation (ddI-EC), and to determine its comparative bioavailability with the ddI pediatric powder for oral solution formulation. 3) To determine the EFV systemic exposure following administration of the currently recommended pediatric doses. 4) To examine in an exploratory analysis, the relationship between antiretroviral systemic exposure for each of the three drugs (FTC/EFV/ddI) and the antiretroviral outcomes as determined by the extent and duration of suppression of plasma HIV-RNA. 5) To determine the distribution of genotypes for cytochrome P450 3A (CYP3A) drug metabolizing enzymes in each subject. 6) To measure CD4 - mediated immune responses to HIV and other microbial antigens and describe their relationship with therapy-induced virologic responses and changes in circulating T cell numbers and phenotype. 7) To measure recent thymic emigrants and determine their relationship with the number of circulating nanve CD4 cells and with virologic response to therapy. 8) To determine the role of antiretroviral resistance in virologic failure of a once-daily treatment regimen of FTC + EFV + ddI, and to evaluate the use of ultrasensitive HIV-RNA determination as an early indicator of virologic failure in treatment-nanve pediatric subjects. 9) To examine in an exploratory analysis whether subjects with poorer adherence to study regimen, have worse virologic responses, or increased risk of virologic failure, or increased risk of developing antiretroviral resistance.