AMPRENAVIR/LOPINAVIR/RITONAVIR IN HIV-INFECTED PATIENTS

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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. Several studies have documented negative interactions between APV and LPV/r and between FPV and LPV/r. The drug interaction for FPV + LPV/r appears to be greater in magnitude than the interaction between APV +LPV/r. In addition, there is the perception that the APV + LPV/r interaction can be overcome by increasing doses of both drugs; whereas, the same strategy is not successful for FPV + LPV/r. However, results from a recently completed study by our group, found that APV (delivered as Agenerase) plasma Cmin plus LPV/r 533mg/133mg BID was comparable to what has been reported by Wire et al. using FPV (delivered as Lexiva)1400mg BID plus LPV/r 533mg/133mg bid. Cross-study comparisons of plasma APV and LPV pharmacokinetics suggest that FPV 1400mg + LPV/r 533mg/133mg BID would deliver bioequivalent plasma LPV exposure compared to LPV/r 400mg/100mg BID and similar plasma APV exposure compared to APV 750mg + LPV 533mg/133mg BID. Since robust comparisons between APV and FPV in combination with LPV/r are lacking, we are proposing open-label study to compare the pharmacokinetics, safety, and efficacy of the prodrug of amprenavir (fosamprenavir; FPV) with the parent drug (amprenavir; APV) when both are coadminstered with LPV/r (with or without EFV).