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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.
J Antimicrob Chemother. 2009 Aug; 64(2):398-410.JA

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+Show Affiliations

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.frNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

19515730

Citation

Molina, Jean-Michel, et al. "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." The Journal of Antimicrobial Chemotherapy, vol. 64, no. 2, 2009, pp. 398-410.
Molina JM, Ait-Khaled M, Rinaldi R, et al. 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. J Antimicrob Chemother. 2009;64(2):398-410.
Molina, J. M., Ait-Khaled, M., Rinaldi, R., Penco, G., Baril, J. G., Cauda, R., Soriano, V., Pialoux, G., Wire, M. B., Lou, Y., Givens, N., Craig, C., Nichols, W. G., Barbosa, I., & Yeo, J. (2009). 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. The Journal of Antimicrobial Chemotherapy, 64(2), 398-410. https://doi.org/10.1093/jac/dkp198
Molina JM, et al. 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. J Antimicrob Chemother. 2009;64(2):398-410. PubMed PMID: 19515730.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 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. AU - Molina,Jean-Michel, AU - Ait-Khaled,Mounir, AU - Rinaldi,Roberto, AU - Penco,Giovanni, AU - Baril,Jean-Guy, AU - Cauda,Roberto, AU - Soriano,Vicente, AU - Pialoux,Gilles, AU - Wire,Mary Beth, AU - Lou,Yu, AU - Givens,Naomi, AU - Craig,Charles, AU - Nichols,W Garrett, AU - Barbosa,Inês, AU - Yeo,Jane, AU - ,, Y1 - 2009/06/10/ PY - 2009/6/12/entrez PY - 2009/6/12/pubmed PY - 2009/9/17/medline SP - 398 EP - 410 JF - The Journal of antimicrobial chemotherapy JO - J Antimicrob Chemother VL - 64 IS - 2 N2 - 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. SN - 1460-2091 UR - https://www.unboundmedicine.com/medline/citation/19515730/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_ L2 - https://academic.oup.com/jac/article-lookup/doi/10.1093/jac/dkp198 DB - PRIME DP - Unbound Medicine ER -