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AIDS. 2018 Jul 17;32(11):1431-1442. doi: 10.1097/QAD.0000000000001817.

A week-48 randomized phase-3 trial of darunavir/cobicistat/emtricitabine/tenofovir alafenamide in treatment-naive HIV-1 patients.

Author information

1
The University of North Carolina School of Medicine, Chapel Hill, North Carolina, USA.
2
Department of Infection and Immunity, Royal London Hospital and Queen Mary University, Barts Health NHS Trust, London, UK.
3
Southwest CARE Center, Santa Fe, New Mexico, USA.
4
Department of Infectious Diseases, St-Louis Hospital APHP, University of Paris Diderot, Paris, France.
5
Lluita contra la Sida Foundation, Germans Trias i Pujol University Hospital, Barcelona, Spain.
6
National Institute for Infectious Diseases, L. Spallanzani IRCCS, Rome, Italy.
7
Southern California Men's Medical Group, Los Angeles, California, USA.
8
Montpellier University Hospital, Montpellier, France.
9
Janssen Pharmaceutica NV, Beerse, Belgium.

Abstract

OBJECTIVES:

To investigate efficacy and safety of a single-tablet regimen of darunavir/cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF) 800/150/200/10 mg vs. darunavir/cobicistat plus emtricitabine/tenofovir disoproxyl fumarate (TDF) (control) in antiretroviral-treatment-naive, HIV-1-infected adults.

DESIGN:

Phase-3, randomized, active-controlled, double-blind, international, multicenter, noninferiority study (NCT02431247).

METHODS:

Seven hundred and twenty-five participants were randomized (1 : 1) to D/C/F/TAF (362) or control (363). The primary objective was to demonstrate noninferiority of D/C/F/TAF vs. control for percentage viral load less than 50 copies/ml (FDA-snapshot analysis) at 48 weeks (10% margin).

RESULTS:

At week 48, D/C/F/TAF was noninferior to control (91.4 vs. 88.4% achieved viral load <50 copies/ml, respectively; difference 2.7%; 95% CI -1.6 to 7.1; P < 0.0001), with 4.4 vs. 3.3% of patients, respectively, having viral load greater or equal to 50 copies/ml. No treatment-emergent mutations associated with darunavir or TAF/TDF resistance were observed in either group. One patient (D/C/F/TAF) was identified with M184I/V conferring resistance to emtricitabine. Incidences of grades 3 and 4 adverse events (5 vs. 6%), serious adverse events (5 vs. 6%) and adverse event-related discontinuations (2 vs. 4%) were low and similar between groups. Mean decrease in urine protein/creatinine ratio was greater with D/C/F/TAF than control (-22.42 vs. -10.34 mg/g, P = 0.033). Mean percentage change in bone mineral density with D/C/F/TAF vs. control was 0.21 vs. -2.73%, P < 0.0001 (hip), -0.68 vs. -2.38%, P = 0.004 (lumbar spine), and -0.26 vs. -2.97%, P < 0.0001 (femoral neck). Median change from baseline in total cholesterol/HDL-cholesterol ratio was 0.20 vs. 0.08, P = 0.036.

CONCLUSION:

D/C/F/TAF achieved a high virologic suppression rate (91.4%) and was noninferior to darunavir/cobicistat with F/TDF. D/C/F/TAF also demonstrated the bone and renal safety advantages of TAF in combination with darunavir/cobicistat.

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