Co-formulated elvitegravir, cobicistat, emtricitabine, and tenofovir disoproxil fumarate versus ritonavir-boosted atazanavir plus co-formulated emtricitabine and tenofovir disoproxil fumarate for initial treatment of HIV-1 infection: A randomised, double-blind, phase 3, non-inferiority trial

Edwin DeJesus, Jürgen K. Rockstroh, Keith Henry, Jean Michel Molina, Joseph Gathe, Srinivasan Ramanathan, Xuelian Wei, Kitty Yale, Javier Szwarcberg, Kirsten White, Andrew K. Cheng, Brian P. Kearney

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328 Scopus citations

Abstract

Background: The HIV integrase strand transfer inhibitor elvitegravir (EVG) has been co-formulated with the CYP3A4 inhibitor cobicistat (COBI), emtricitabine (FTC), and tenofovir disoproxil fumarate (TDF) into a once-daily, single tablet. We compared EVG/COBI/FTC/TDF with a ritonavir-boosted (RTV) protease inhibitor regimen of atazanavir (ATV)/RTV+FTC/TDF as initial therapy for HIV-1 infection. Methods: This phase 3, non-inferiority study enrolled treatment-naive patients with an HIV-1 RNA concentration of 5000 copies per mL or more and susceptibility to atazanavir, emtricitabine, and tenofovir. Patients were randomly assigned (1:1) to receive EVG/COBI/FTC/TDF or ATV/RTV+FTC/TDF plus matching placebos, administered once daily. Randomisation was by a computer-generated random sequence, accessed via an interactive telephone and web response system. Patients, and investigators and study staff who gave treatments, assessed outcomes, or analysed data were masked to the assignment. The primary endpoint was HIV RNA concentration of 50 copies per mL or less after 48 weeks (according to the US FDA snapshot algorithm), with a 12% non-inferiority margin. This trial is registered with ClinicalTrials.gov, number NCT01106586. Findings: 1017 patients were screened, 715 were enrolled, and 708 were treated (353 with EVG/COBI/FTC/TDF and 355 with ATV/RTV+FTC/TDF). EVG/COBI/FTC/TDF was non-inferior to ATV/RTV+FTC/TDF for the primary outcome (316 patients [89·5%] vs 308 patients [86·8%], adjusted difference 3·0%, 95% CI -1·9% to 7·8%). Both regimens had favourable safety and tolerability; 13 (3·7%) versus 18 (5·1%) patients discontinued treatment because of adverse events. Fewer patients receiving EVG/COBI/FTC/TDF had abnormal results in liver function tests than did those receiving ATV/RTV+FTC/TDF and had smaller median increases in fasting triglyceride concentration (90 μmol/L vs 260 μmol/L, p=0·006). Small median increases in serum creatinine concentration with accompanying decreases in estimated glomerular filtration rate occurred in both study groups by week 2; they generally stabilised by week 8 and did not change up to week 48 (median change 11 μmol/L vs 7 μmol/L). Interpretation: If regulatory approval is given, EVG/COBI/FTC/TDF would be the first integrase-inhibitor-based regimen given once daily and the only one formulated as a single tablet for initial HIV treatment.

Original languageEnglish (US)
Pages (from-to)2429-2438
Number of pages10
JournalThe Lancet
Volume379
Issue number9835
DOIs
StatePublished - Jun 2012

Bibliographical note

Funding Information:
EDJ has received research grant support from Abbott Laboratories, Achillion Pharmaceuticals, Avexa, Boehringer Ingelheim, Bristol-Myers Squibb, Gilead Sciences, GlaxoSmithKline, Hoffmann LaRoche, Idenix, Janssen, Merck, Pfizer, Sangamo, Taimed, Tobira, and Vertex; and consulting fees as a member of advisory boards for Bristol-Myers Squibb, Gilead Sciences, Janssen, Merck, and Vertex. JR has received lecture fees and advisory board honoraria from Abbot Laboratories, Bionor, Gilead Sciences, Boehringer Ingelheim, Bristol-Myers Squibb, Merck, Novartis, Pfizer, Roche, Tibotec, and Viiv Healthcare. KH has received research grant support from Gilead Sciences, GlaxoSmithKline, US Centers for Disease Control, and the US National Institutes of Health; consulting fees as an advisory board member for Gilead Sciences. J-MM has acted as a consultant, participated in advisory boards, has received speaker fees, and has been an investigator for clinical trials for Abbott, Boehringer Ingelheim, Bristol-Myers Squibb, Gilead Sciences, Merck, Tibotec, and ViiV Healthcare. JG has received research grant support from Abbott Laboratories, Boehringer Ingelheim, Gilead Sciences, GlaxoSmithKline, Janssen, and receives consulting fees from Abbott Laboratories and Boehringer Ingelheim. SR, XW, KY, JS, KW, AC, and BPK are employees of Gilead Sciences.

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