Fosamprenavir Clinical Study Meta-Analysis in ART-Naïve Subjects: Rare Occurrence of Virologic Failure and Selection of Protease-Associated Mutations

Abstract

Background:In recent ritonavir-boosted protease inhibitor (PI) studies, high efficacy rates have been observed, with few PI mutations detected. Method: To better understand the types of mutations observed and their phenotypic impact and the likelihood of virologic failure (VF) on a regimen that includes either a ritonavir-boosted or unboostedPI, fosamprenavir, a meta-analysis of three studies (NEAT, SOLO, and KLEAN) of 922 ART-naïve participants receiving boosted (FPV/r) or unboosted fosamprenavir (FPV) plus abacavir/lamivudine was performed. 70% of participants by the missing and discontinuation equals failure analysis and 95% by the observed analysis had HIV-RNA <400 copies/mL through 48 weeks. Paired genotypes (baseline and follow-up) were obtained for 74/85 participants meeting VF analysis criteria. Results: FPV-associated resistance mutations were detected in 5/74 patients with VF, with 4/5 receiving unboosted FPV; in four patients viruses developed I54L or M andone developed the V32I+I47V combination. No virus from patients with VF receiving FPV/r had reduced FPV susceptibility (RS), whereasvirus from 3/4 of participants with VF who received unboosted FPV and who acquired FPV mutations had FPV RS. Little PI cross-resistance was detected in the VF virus; RS was observed for lopinavir, saquinavir, nelfinavir, atazanavir, and indinavir in 0, 0, 2, 0, and 1 of 5 subjects, respectively. Conclusion: These data suggest that inclusion of FPV as part of an initial HIV-treatment regimen is associated with low rates of VF. Selection of FPV resistance-associated mutations is unlikely, especially for FPV/r-containing regimens. If selection of FPV-associated mutations does occur, a second-line PI-containing regimen can be easily constructed.

Keywords:

• boosted PI
• fosamprenavir
• HIV
• mutations
• phenotype
• protease inhibitor
• resistance