PACTG(PEDIATRIC AIDS CLINICAL TRIAL GROUP) 1058 : PHARMACOKINETIC STUDIES

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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. Antiretroviral therapy for HIV-infected children has become highly complex and individualized due to extensive antiretroviral treatment experience, the availability of 20 different antiretroviral drugs, and the ability to define complex resistance patterns by genotypic and phenotypic testing. Rather than using a small number of tested fixed drug combinations, clinicians are basing treatment decisions on factors such as palatability, tolerability, safety, convenience, and most prominently, resistance patterns. Cross-resistance between antiretrovirals leads to situations where it is not possible to construct a regimen likely to achieve and maintain an undetectable viral load without using combinations, often of 4 or more drugs, that have not been studied in children (and often not in adults). Because all of the available non-nucleoside reverse transcriptase inhibitors (NNRTIs) and HIV protease inhibitors (PIs) are metabolized by and affect hepatic cytochrome systems (through induction, inhibition, or both mechanisms), combinations of two or more of these drugs produce complex pharmacokinetic interactions. In addition to the deficit of information on interacting drug combinations, many of the licensed antiretrovirals do not have FDA-approved labeling for children or for children below a certain age. This study proposes to investigate the pharmacokinetic (PK) interactions in children of several popular drug regimens for which no PK data is currently available.