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Clinical Trial
. 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

Joseph J Eron  1 , Chloe Orkin  2 , Joel Gallant  3 , Jean-Michel Molina  4 , Eugenia Negredo  5 , Andrea Antinori  6 , Anthony Mills  7 , Jacques Reynes  8 , Erika Van Landuyt  9 , Erkki Lathouwers  9 , Veerle Hufkens  9 , John Jezorwski  9 , Simon Vanveggel  9 , Magda Opsomer  9 ; AMBER study group
Affiliations
Clinical Trial

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

Joseph J Eron et al. AIDS. .

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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Figures

Fig. 1
Fig. 1
Patient disposition through 48 weeks.
Fig. 2
Fig. 2
Week-48 Food and Drug Administration-snapshot analysis (<50 copies/ml).
Fig. 3
Fig. 3
Mean change from baseline to week 48 in kidney and bone parameters.
See this image and copyright information in PMC

References

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