PMID- 19515730 OWN - NLM STAT- MEDLINE DCOM- 20090916 LR - 20201209 IS - 1460-2091 (Electronic) IS - 0305-7453 (Linking) VI - 64 IP - 2 DP - 2009 Aug TI - 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. PG - 398-410 LID - 10.1093/jac/dkp198 [doi] AB - 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. FAU - Molina, Jean-Michel AU - Molina JM AD - Service des Maladies Infectieuses et Tropicales, Hopital Saint-Louis and University of Paris Diderot, Paris 7, 1 Avenue Claude-Vellefaux, 75475 Paris Cedex 10, France. jean-michel.molina@sls.aphp.fr FAU - Ait-Khaled, Mounir AU - Ait-Khaled M FAU - Rinaldi, Roberto AU - Rinaldi R FAU - Penco, Giovanni AU - Penco G FAU - Baril, Jean-Guy AU - Baril JG FAU - Cauda, Roberto AU - Cauda R FAU - Soriano, Vicente AU - Soriano V FAU - Pialoux, Gilles AU - Pialoux G FAU - Wire, Mary Beth AU - Wire MB FAU - Lou, Yu AU - Lou Y FAU - Givens, Naomi AU - Givens N FAU - Craig, Charles AU - Craig C FAU - Nichols, W Garrett AU - Nichols WG FAU - Barbosa, Ines AU - Barbosa I FAU - Yeo, Jane AU - Yeo J CN - TRIAD Study Group LA - eng PT - Journal Article PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20090610 PL - England TA - J Antimicrob Chemother JT - The Journal of antimicrobial chemotherapy JID - 7513617 RN - 0 (Anti-HIV Agents) RN - 0 (Carbamates) RN - 0 (Furans) RN - 0 (Organophosphates) RN - 0 (Sulfonamides) RN - O3J8G9O825 (Ritonavir) RN - WOU1621EEG (fosamprenavir) SB - IM MH - Adult MH - Aged MH - Anti-HIV Agents/administration & dosage/adverse effects/*therapeutic use MH - Carbamates/administration & dosage/adverse effects/*therapeutic use MH - *Drug Resistance, Viral MH - Female MH - Furans MH - HIV Infections/*drug therapy/virology MH - HIV-1/*drug effects MH - Humans MH - Male MH - Middle Aged MH - Organophosphates/administration & dosage/adverse effects/*therapeutic use MH - Ritonavir/administration & dosage/adverse effects/*therapeutic use MH - Sulfonamides/administration & dosage/adverse effects/*therapeutic use MH - Treatment Outcome MH - Viral Load FIR - Cooper, David IR - Cooper D FIR - Clumeck, Nathan IR - Clumeck N FIR - Trottier, Sylvie IR - Trottier S FIR - Smith, Graham IR - Smith G FIR - Logue, Ken IR - Logue K FIR - Conway, Brian IR - Conway B FIR - Tsoukas, Christos IR - Tsoukas C FIR - Partisiani, Maria-Louisa IR - Partisiani ML FIR - Sereni, Daniel IR - Sereni D FIR - Lafeuillade, Alain IR - Lafeuillade A FIR - Bergmann, Jean-Francois IR - Bergmann JF FIR - Khuong-Josses, Marie-Aude IR - Khuong-Josses MA FIR - Bouchaud, Olivier IR - Bouchaud O FIR - Plettenberg, Andreas IR - Plettenberg A FIR - Gargalianos-Kakolyris, Panagiotis IR - Gargalianos-Kakolyris P FIR - Chrysos, George IR - Chrysos G FIR - Sighinolfi, Laura IR - Sighinolfi L FIR - Mazzotta, Francesco IR - Mazzotta F FIR - Filice, Gaetano IR - Filice G FIR - Caramello, Pietro IR - Caramello P FIR - Blanco, Francisco IR - Blanco F FIR - Domingo, Pere IR - Domingo P FIR - Estrada, Vicente IR - Estrada V FIR - Pulido, Federico IR - Pulido F FIR - Terron, Jose Alberto IR - Terron JA FIR - Gorgolas, Miguel IR - Gorgolas M FIR - Coll, Blai IR - Coll B FIR - Portilla, Joaquin IR - Portilla J FIR - Johnson, Margaret IR - Johnson M FIR - Huengsberg, Mia IR - Huengsberg M FIR - Easterbrook, Phillipa IR - Easterbrook P FIR - Winston, Alan IR - Winston A EDAT- 2009/06/12 09:00 MHDA- 2009/09/17 06:00 CRDT- 2009/06/12 09:00 PHST- 2009/06/12 09:00 [entrez] PHST- 2009/06/12 09:00 [pubmed] PHST- 2009/09/17 06:00 [medline] AID - dkp198 [pii] AID - 10.1093/jac/dkp198 [doi] PST - ppublish SO - J Antimicrob Chemother. 2009 Aug;64(2):398-410. doi: 10.1093/jac/dkp198. Epub 2009 Jun 10.