PACTG P1038: LOPINAVIR/RITONAVIR IN PEDIATRIC SUBJECTS WITH HIV PREVIOUSLY TREAT

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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. There are limited options available for HIV-infected children who have previously failed antiretroviral therapy (ART). This is a proof-of-concept study designed to examine the feasibility of treating HIV-infected children who have failed protease inhibitor (PI)-containing ART with high doses of Lopinavir/Ritonavir (LPV/r). The primary objectives are to estimate the pharmacokinetic parameters for LPV/r and saquinavir (SQV) and to examine the safety of LPV/r and SQV at higher doses. The primary endpoints are life threatening adverse events and dose-limiting toxicity. This is a phase I/II open-label study. Subjects who are failing their current therapy and have at least 4 of the required PI mutations and have a phenotype that shows >5-fold resistance than wild type will enter Step 1 and will be stratified by NNRTI use. Group 1 is LPV/r and 2 NRTIs and no NNRTI vs Group 2, which have NNRTI. After 2 weeks, LPV/r drug levels will be obtained. If the inhibitory quotient (IQ) is <15, the subjects add SQV. After 2 weeks, SQV drug levels will be obtained. If the level is <500 ng/ml, subjects proceed to Step 3 and increase the SQV dose. This is a very important study. There are limited options for these children, and this study explores the use of high doses of 2 PIs in order to achieve concentrations in the blood that will be effective in reducing the HIV viral load, which ultimately will slow the progression of this disease.