Background: Darunavir/cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF) 800/150/200/10 mg is a once-daily, single-tablet regimen approved in Europe and under regulatory review in the US for the treatment of HIV-1 infection. In the pivotal AMBER trial in antiretroviral treatment (ART)-naïve, HIV-1infected adults, D/C/F/TAF achieved a high virologic response rate at Week 48 that was non-inferior to control (D/C+F/tenofovir disoproxil fumarate); favorable renal/bone outcomes were seen with D/C/F/TAF versus control. These results were consistent across age, gender, and race subgroups. Here we report Week 48 results in subgroups based on viral load (VL), CD4+ count, and WHO clinical staging of HIV/AIDS at baseline.
Methods: The phase 3, randomized (1:1), blinded, non-inferiority AMBER trial enrolled ART-naïve, HIV-1infected adults. The primary endpoint was the proportion of patients with virologic response (VL <50 copies/mL; FDA snapshot) at Week 48. Adverse events (AEs) and laboratory parameters were monitored throughout the study. Results were evaluated in subgroups based on VL (≤ vs >100,000 copies/mL), CD4+ count (< vs ≥350 cells/µL), and WHO clinical stage (1 vs 2 vs 3 vs 4) at baseline.
Results: Of the 725 patients randomized and treated, the majority had VL ≤100,000 copies/mL (82% of patients), CD4+ count ≥350 cells/µL (72%), and WHO clinical stage 1 (84%) at baseline. Overall virologic response rates were 91.4% with D/C/F/TAF and 88.4% with control; results were similar across baseline VL, CD4+ count, and WHO clinical stage subgroups (Figure). Overall rates of serious AEs, grade 3-4 AEs, and AE-related discontinuations were similar for D/C/F/TAF (n=17 [4.7%], n=19 [5.2%], and n=7 [1.9%], respectively) and control (n=21 [5.8%], n=22 [6.1%], and n=16 [4.4%]), as well as across subgroups (Table).
Conclusion: D/C/F/TAF achieved high (91.4%), non-inferior virologic response rates versus control (88.4%) in ART-naïve, HIV-1infected adults. Consistent and robust efficacy and safety results were found with D/C/F/TAF versus control based on VL, CD4+ count, and WHO clinical stage at baseline.
C. D. Spinner,
C. Mcdonald, Gilead: Various , Personal fees . Merck: Various , Personal fees . ViiV: Various , Personal fees . Janssen: Various , Personal fees .
C. Mussini, None
D. Luo, Janssen: Employee , Salary .
J. Jezorwski, Janssen: Employee , Salary .
K. Brown, Janssen: Employee , Salary .
E. Y. Wong, Janssen: Employee , Salary .