title: Fosamprenavir/ritonavir in advanced HIV disease (TRIAD): a randomized study of high-dose, dual-boosted or standard dose fosamprenavir/ritonavir in HIV-1-infected patients with antiretroviral resistance.
abstract: BACKGROUND
  APV102002 was an open-label study comparing a dual-boosted HIV-1 protease inhibitor (PI) [fosamprenavir/lopinavir/ritonavir (FPV/LPV/RTV; 1400 mg/533 mg/133 mg twice daily)] and a high dose of FPV/RTV 1400 mg/100 mg twice daily (HD-FPV/RTV) versus the standard FPV/RTV 700 mg/100 mg twice-daily (STD-FPV/RTV) regimen for 24 weeks.
  
  
  METHODS
  Adult patients with prior failure to two or more PI-based regimens and on a failing PI regimen were randomized to STD-FPV/RTV (n = 24), HD-FPV/RTV (n = 25) or FPV/LPV/RTV (n = 25). The primary aim was to test week 24 superiority of HD-FPV/RTV and FPV/LPV/RTV over STD-FPV/RTV as measured by plasma HIV-1 RNA average area under the curve minus baseline (AAUCMB).
  
  
  RESULTS
  There was no difference in the week 24 AAUCMB between the regimens. The proportion of patients with <50 copies/mL of plasma HIV RNA was 21%, 24% and 20%, respectively, by time to loss of virological response (TLOVR) analysis. High baseline drug resistance provided some explanation for the low efficacy. A lower baseline background drug resistance and higher fosamprenavir genotypic inhibitory quotient led to better antiviral responses. The plasma amprenavir trough concentartion (C(tau)) was 49% higher in the HD-FPV/RTV arm than in the STD-FPV/RTV arm and similar in the FPV/LPV/RTV and STD-FPV/RTV arms. The plasma lopinavir C(tau) was similar to historical data with standard LPV/RTV 400 mg/100 mg twice daily. All regimens were relatively well tolerated, although diarrhoea was more frequent in the HD-FPV/RTV and FPV/LPV/RTV arms, and hypertriglyceridaemia and increased total cholesterol were more common in the FPV/LPV/RTV arm.
  
  
  CONCLUSIONS
  While the strategies of higher dose FPV/RTV and dual FPV/LPV/RTV were relevant at the time of study initiation, new therapies for antiretroviral-experienced patients make such strategies of limited interest. In addition, this study failed to demonstrate antiviral superiority of the HD-FPV/RTV or FPV/LPV/RTV regimen over the STD-FPV/RTV twice-daily regimen in highly treatment-experienced patients.
authors.affiliation: Service des Maladies Infectieuses et Tropicales, Hôpital Saint-Louis and University of Paris Diderot, Paris 7, 1 Avenue Claude-Vellefaux, 75475 Paris Cedex 10, France. jean-michel.molina@sls.aphp.fr
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Molina
authors.forename: Mounir
authors.initials: M
authors.lastname: Ait-Khaled
authors.forename: Roberto
authors.initials: R
authors.lastname: Rinaldi
authors.forename: Giovanni
authors.initials: G
authors.lastname: Penco
authors.forename: Jean-Guy
authors.initials: JG
authors.lastname: Baril
authors.forename: Roberto
authors.initials: R
authors.lastname: Cauda
authors.forename: Vicente
authors.initials: V
authors.lastname: Soriano
authors.forename: Gilles
authors.initials: G
authors.lastname: Pialoux
authors.forename: Mary Beth
authors.initials: MB
authors.lastname: Wire
authors.forename: Yu
authors.initials: Y
authors.lastname: Lou
authors.forename: Naomi
authors.initials: N
authors.lastname: Givens
authors.forename: Charles
authors.initials: C
authors.lastname: Craig
authors.forename: W Garrett
authors.initials: WG
authors.lastname: Nichols
authors.forename: Inês
authors.initials: I
authors.lastname: Barbosa
authors.forename: Jane
authors.initials: J
authors.lastname: Yeo
mesh_terms: D000328:Adult; D000368:Aged; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D002219:Carbamates / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D024882:Drug Resistance, Viral; D005260:Female; D005663:Furans; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010755:Organophosphates / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D019438:Ritonavir / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D013449:Sulfonamides / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome; D019562:Viral Load
chemical_list: D019380:Anti-HIV Agents; D002219:Carbamates; D005663:Furans; D010755:Organophosphates; D013449:Sulfonamides; D019438:Ritonavir; C426859:fosamprenavir