A week-48 randomized phase-3 trial of darunavir/cobicistat/emtricitabine/tenofovir alafenamide in treatment-naive HIV-1 patients.
AIDS
; 32(11): 1431-1442, 2018 07 17.
Article
in En
| MEDLINE
| ID: mdl-29683855
ABSTRACT
OBJECTIVES:
To investigate efficacy and safety of a single-tablet regimen of darunavir/cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF) 800/150/200/10âmg 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 (1ââ1) 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 50âcopies/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; Pâ<â0.0001), with 4.4 vs. 3.3% of patients, respectively, having viral load greater or equal to 50âcopies/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. -10.34âmg/g, Pâ=â0.033). Mean percentage change in bone mineral density with D/C/F/TAF vs. control was 0.21 vs. -2.73%, Pâ<â0.0001 (hip), -0.68 vs. -2.38%, Pâ=â0.004 (lumbar spine), and -0.26 vs. -2.97%, Pâ<â0.0001 (femoral neck). Median change from baseline in total cholesterol/HDL-cholesterol ratio was 0.20 vs. 0.08, Pâ=â0.036.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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
HIV Infections
/
Anti-HIV Agents
Type of study:
Clinical_trials
/
Incidence_studies
/
Prognostic_studies
Limits:
Adolescent
/
Adult
/
Aged
/
Aged80
/
Female
/
Humans
/
Male
/
Middle aged
Language:
En
Journal:
AIDS
Journal subject:
SINDROME DA IMUNODEFICIENCIA ADQUIRIDA (AIDS)
Year:
2018
Document type:
Article
Affiliation country:
United States
Publication country:
ENGLAND
/
ESCOCIA
/
GB
/
GREAT BRITAIN
/
INGLATERRA
/
REINO UNIDO
/
SCOTLAND
/
UK
/
UNITED KINGDOM