title: Long-term safety study of fosamprenavir-containing regimens in HIV-1-infected patients.
abstract: BACKGROUND
  Safety and efficacy of the protease inhibitor fosamprenavir (FPV) ± ritonavir (r) was evaluated in 3 pivotal 48-week phase III studies. A follow-on study provides long-term data on FPV-based regimens.
  
  
  METHODS
  International, multicenter, uncontrolled open-label study APV30005 provided FPV as part of combination therapy to HIV-1-infected patients aged ≥13 years who had participated in previous FPV and amprenavir studies. Regimens included FPV/r 1400/200 mg once daily, FPV/r 700/100 mg twice daily, or FPV 1400 mg twice daily. Safety and efficacy were evaluated every 12 weeks, including incidence and frequency of adverse events and laboratory abnormalities, plasma HIV-1 RNA levels, CD4+ cell counts, and frequency of HIV disease progression. Because this was a nonrandomized, observational study, no significance testing was performed.
  
  
  RESULTS
  Overall, 753 patients were enrolled. The most common reasons for premature discontinuation were lost to follow-up (88 [12%]) and insufficient viral load response (69 [9%]). The majority of patients had ≯192 weeks exposure to FPV, with 53 patients exposed for more than 8 years. Drug-related grade 2-4 adverse events were reported for 250 patients (33%), with the majority reported in the first 48 weeks of the study. Most commonly reported grade 3/4 laboratory parameters were increased lipase, triglycerides, and elevated liver enzymes. The observed proportions of patients with plasma HIV-1 RNA levels <50 copies/mL remained ≯70% from week 48 onwards.
  
  
  CONCLUSIONS
  Extended treatment of up to 8 years with FPV-containing regimens revealed no new safety concerns and was associated with sustained antiviral responses.
authors.affiliation: Desmond Tutu HIV Centre, Institute of Infectious Disease and Molecular Medicine, Department of Medicine, University of Cape Town, Observatory, South Africa.
authors.forename: Robin
authors.initials: R
authors.lastname: Wood
authors.forename: Joseph C
authors.initials: JC
authors.lastname: Gathe
authors.forename: Naomi
authors.initials: N
authors.lastname: Givens
authors.forename: Sangeeta
authors.initials: S
authors.lastname: Sedani
authors.forename: Katharine
authors.initials: K
authors.lastname: Cheng
authors.forename: Jörg
authors.initials: J
authors.lastname: Sievers
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D019380:Anti-HIV Agents / Q000009:adverse effects* / Q000627:therapeutic use*; D002219:Carbamates / Q000009:adverse effects* / Q000627:therapeutic use*; D005260:Female; D005663:Furans; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D015497:HIV-1; D006801:Humans; D008297:Male; D008875:Middle Aged; D010755:Organophosphates / Q000009:adverse effects* / Q000627:therapeutic use*; D012367:RNA, Viral; D013449:Sulfonamides / Q000009:adverse effects* / Q000627:therapeutic use*; D019562:Viral Load; D055815:Young Adult
chemical_list: D019380:Anti-HIV Agents; D002219:Carbamates; D005663:Furans; D010755:Organophosphates; D012367:RNA, Viral; D013449:Sulfonamides; C095108:amprenavir; C426859:fosamprenavir
keywords: fosamprenavir; long-term safety; protease inhibitors