Randomized, phase 2 evaluation of two single-tablet regimens elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate versus efavirenz/emtricitabine/tenofovir disoproxil fumarate for the initial treatment of HIV infection

被引:93
作者
Cohen, Calvin [1 ]
Elion, Richard [1 ]
Ruane, Peter [1 ]
Shamblaw, David [1 ]
DeJesus, Edwin [1 ]
Rashbaum, Bruce [1 ]
Chuck, Steven L. [1 ]
Yale, Kitty [1 ]
Liu, Hui C. [1 ]
Warren, David R. [1 ]
Ramanathan, Srinivasan [1 ]
Kearney, Brian P. [1 ]
机构
[1] Gilead Sci Inc, Foster City, CA 94404 USA
关键词
booster; GS-9137; GS-9350; integrase inhibitor; JTK-303; quad; treatment-naive; TREATMENT-NAIVE PATIENTS; ANTIRETROVIRAL THERAPY; COMBINATION THERAPY; INTEGRASE INHIBITOR; DOSE-RESPONSE; EFAVIRENZ; PHARMACOKINETICS; RALTEGRAVIR; TRIAL; ELVITEGRAVIR;
D O I
10.1097/QAD.0b013e328345766f
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Objective: To assess the safety and efficacy of two, single-tablet regimens for the initial treatment of HIV infection. Design: Phase 2, randomized, double-blind, double-dummy, multicenter, active-controlled study. Methods: Antiretroviral treatment-naive adults with a screening HIV-1 RNA at least 5000 copies/ml and a CD4 cell count more than 50 cells/mu l were randomized 2 : 1 to receive fixed-dose combination tablets of elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate (EVG/COBI/FTC/TDF; N = 48) or efavirenz/emtricitabine/tenofovir disoproxil fumarate (EFV/FTC/TDF; n = 23) for 48 weeks. The primary endpoint was proportion of participants with HIV-1 RNA less than 50 copies/ml at week 24. Results: Participants receiving EVG/COBI/FTC/TDF exhibited a more rapid decline in HIV-1 RNA and a greater proportion suppressed viral load to less than 50 copies/ml than participants receiving EFV/FTC/TDF. Both EVG/COBI/FTC/TDF and EFV/FTC/TDF resulted in high rates of viral suppression and increases in CD4 cell count. Ninety and 83% of participants suppressed HIV-1 RNA to less than 50 copies/ml both at the 24-week and 48-week visits for EVG/COBI/FTC/TDF and EFV/FTC/TDF, respectively. Once-daily administration of EVG/COBI/FTC/TDF provided a mean EVG trough concentration 10-fold over its protein binding-adjusted IC95 across study visits. EVG/FTC/TDF/GS-9350 was generally well tolerated with a lower rate of drug-related central nervous system (17%) and psychiatric (10%) adverse events versus EFV/FTC/TDF (26 and 44%, respectively). Decreases in estimated glomerular filtration rate occurred within the first few weeks of dosing in participants receiving EVG/COBI/FTC/TDF, remained within the normal range and did not progress at week 24 or 48; no participant experienced a clinical adverse event or discontinued study drug due to changes in serum creatinine or renal function. Conclusion: Once-daily EVG/COBI/FTC/TDF achieved and maintained a high rate of virologic suppression with fewer central nervous system and psychiatric adverse events compared to a current standard-of-care regimen of EFV/FTC/TDF. (c) 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins
引用
收藏
页码:F7 / F12
页数:6
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