Darunavir/cobicistat/emtricitabine/tenofovir alafenamide in treatment-naïve patients with HIV-1: subgroup analyses of the phase 3 AMBER study

Abstract

Background: The once-daily, single-tablet regimen darunavir/cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF) 800/150/200/10 mg is approved for the treatment of HIV-1 infection. The 48-week efficacy and safety of D/C/F/TAF versus darunavir/cobicistat + emtricitabine/tenofovir disoproxil fumarate (control) in treatment-naïve adults were demonstrated in the phase 3 AMBER study. Objective: To describe AMBER outcomes across patient subgroups based on demographic and clinical characteristics at baseline. Methods: AMBER patients had viral load (VL) ≥1000 copies/mL, CD4⁺ cell count >50 cells/µL, and genotypic susceptibility to darunavir, emtricitabine, and tenofovir. Primary endpoint was the proportion of patients with virologic response (VL <50 copies/mL; FDA snapshot). Safety was assessed by adverse events, estimated glomerular filtration rate (cystatin C; eGFR_cystC), and bone mineral density. Outcomes were assessed by age (≤/>50 years), gender, race (black/non-black), baseline VL (≤/>100,000 copies/mL), baseline CD4⁺ cell count (</≥200 cells/µL), and baseline WHO clinical stage of HIV infection (1/2). Results: For the 725 AMBER patients (D/C/F/TAF: 362; control: 363), virologic response rates at week 48 were similar with D/C/F/TAF (91%) and control (88%), and this was consistent across all subgroups. Adverse event rates were similar in both arms, although numerically higher among patients >50 years and women, relative to their comparator groups, regardless of treatment arm (notably, sample sizes were small for patients >50 years and women). Improvements in eGFR_cystC and stable bone mineral density were observed with D/C/F/TAF overall, and results were generally consistent across subgroups. Conclusions: For treatment-naïve patients in AMBER, initiating therapy with the D/C/F/TAF single-tablet regimen was an effective and well-tolerated option, regardless of demographic or clinical characteristics.

Trial registration: ClinicalTrials.gov NCT02431247.

Keywords: HIV-1; antiretroviral; darunavir; protease inhibitor; single-tablet regimen; tenofovir alafenamide; treatment initiation.