title: 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.
  
  
  METHODS
  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 unboosted PI, 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 and one developed the V32I+I47V combination. No virus from patients with VF receiving FPV/r had reduced FPV susceptibility (RS), whereas virus 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: GlaxoSmithKline, Research Triangle Park, North Carolina 27709, USA. lisa.l.ross@gsk.com
authors.forename: Lisa
authors.initials: L
authors.lastname: Ross
authors.forename: Cindy
authors.initials: C
authors.lastname: Vavro
authors.forename: Brian
authors.initials: B
authors.lastname: Wine
authors.forename: Qiming
authors.initials: Q
authors.lastname: Liao
mesh_terms: D019380:Anti-HIV Agents / Q000494:pharmacology*; D023241:Antiretroviral Therapy, Highly Active; D002219:Carbamates / Q000494:pharmacology*; D004347:Drug Interactions; D024882:Drug Resistance, Viral / Q000235:genetics*; D005663:Furans; D015658:HIV Infections / Q000188:drug therapy; D016333:HIV Protease / Q000235:genetics* / Q000378:metabolism; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics; D006801:Humans; D009154:Mutation / Q000235:genetics; D010755:Organophosphates / Q000494:pharmacology*; D012641:Selection, Genetic; D013449:Sulfonamides / Q000494:pharmacology*; D016896:Treatment Outcome
chemical_list: D019380:Anti-HIV Agents; D002219:Carbamates; D005663:Furans; D010755:Organophosphates; D013449:Sulfonamides; D016333:HIV Protease; C426859:fosamprenavir