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
Por:
Molina, JM, Ait-Khaled, M, Rinaldi, R, Penco, G, Baril, JG, Cauda, R, Soriano, V, Pialoux, G, Wire, MB, Lou, Y, Givens, N, Craig, C, Nichols, WG, Barbosa, I, Yeo, J, Domingo P., TRIAD Study Grp
Publicada:
1 ago 2009
Resumen:
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.
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).
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.
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.
Filiaciones:
Molina, JM:
Hop St Louis, Serv Malad Infect & Trop, F-75475 Paris 10, France
Univ Paris 07, F-75475 Paris 10, France
Ait-Khaled, M:
GlaxoSmithKline, Greenford UB6 0HE, Middx, England
Rinaldi, R:
Azienda Osped Padova, Div Malattie Infett & Trop, I-35128 Padua, Italy
Penco, G:
EO Osped Galliera, I-16128 Genoa, Italy
Baril, JG:
Clin Med Quartier Latin, Montreal, PQ H2L 5B1, Canada
Cauda, R:
Univ Cattolica Sacro Cuore, Ist Clin Malattie Infett, I-00168 Rome, Italy
Soriano, V:
Hosp Carlos III, Dept Infect Dis, Madrid 28090, Spain
Pialoux, G:
Hop Tenon, Serv Malad Infect, F-75970 Paris 20, France
Wire, MB:
GlaxoSmithKline, Res Triangle Pk, NC USA
Lou, Y:
GlaxoSmithKline, Res Triangle Pk, NC USA
Givens, N:
GlaxoSmithKline, Greenford UB6 0HE, Middx, England
Craig, C:
GlaxoSmithKline, Int Clin Virol, Stevenage SG1 2NY, Herts, England
Nichols, WG:
GlaxoSmithKline, Greenford UB6 0HE, Middx, England
Barbosa, I:
GlaxoSmithKline, Greenford UB6 0HE, Middx, England
Yeo, J:
GlaxoSmithKline, Greenford UB6 0HE, Middx, England
Domingo P.:
Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
Institut dInvestigació Biomèdica Sant Pau IIB Sant Pau, Barceona, Spain
Universitat Autònoma de Barcelona, Cerdanyola del Valles, Spain
Bronze
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