Darunavir/cobicistat/emtricitabine/tenofovir alafenamide in treatment-experienced, virologically suppressed patients with HIV-1: subgroup analyses of the phase 3 EMERALD study

Abstract

Background Darunavir/cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF) 800/150/200/10 mg is a once-daily, single-tablet regimen for treatment of HIV-1 infection. The efficacy/safety of switching to D/C/F/TAF versus continuing boosted protease inhibitor (bPI) + emtricitabine/tenofovir disoproxil fumarate (control) were demonstrated in a phase 3, randomized study (EMERALD) of treatment-experienced, virologically suppressed adults through week 48. The objective of this analysis was to evaluate EMERALD outcomes across subgroups of patients based on demographic characteristics, prior treatment experience, and baseline antiretroviral regimen. Methods EMERALD patients were virologically suppressed (viral load [VL] < 50 copies/mL for ≥ 2 months at screening). Prior non-darunavir virologic failure (VF) was allowed. Primary endpoint was proportion of patients with virologic rebound (confirmed VL ≥ 50 copies/mL) cumulative through week 48. Virologic response was VL < 50 copies/mL (FDA snapshot). Safety was assessed by adverse events, renal proteinuria markers, and bone mineral density. Outcomes were examined for prespecified subgroups by age (≤/> 50 years), gender, race (black/non-black), prior number of antiretrovirals used (4/5/6/7/> 7), prior VF (0/≥ 1), baseline bPI (darunavir/atazanavir or lopinavir), and baseline boosting agent (ritonavir/cobicistat). Results Among 1141 patients in the D/C/F/TAF (n = 763) and control (n = 378) arms, virologic rebound rates (2.5% and 2.1%, respectively) were similar, and this was consistent across all subgroups. Virologic response rates ranged from 91 to 97% (D/C/F/TAF) and 89 to 99% (control) across all subgroups, with differences between treatment arms of 0 and 6%. Adverse event rates were low in both arms and across subgroups. Improvements in renal and bone parameters were observed with D/C/F/TAF across demographic subgroups. Conclusions For treatment-experienced, virologically suppressed patients, switching to D/C/F/TAF was highly effective and safe, regardless of demographic characteristics, prior treatment experience, or pre-switch bPI. Trial registration ClinicalTrials.gov Identifier: NCT02269917. Registered 21 October 2014. https://clinicaltrials.gov/ct2/show/NCT02269917 Electronic supplementary material The online version of this article (10.1186/s12981-019-0235-1) contains supplementary material, which is available to authorized users.

Week 48 Resistance Analyses of the Once-Daily, Single-Tablet Regimen Darunavir/Cobicistat/Emtricitabine/Tenofovir Alafenamide (D/C/F/TAF) in Adults Living with HIV-1 from the Phase III Randomized AMBER and EMERALD Trials

“…Subgroup analyses by previous antiretroviral use and VF showed no effect on rebound rates, virologic response, and VF rates by the FDAsnapshot analysis. 11,34 There was no exclusion on the basis of tenofovir or emtricitabine RAMs. In EMERALD D/C/F/TAF participants with previous VF (n = 98) at baseline, 37% (n = 36) had HIV-1 not fully susceptible to emtricitabine and 22% (n = 22) not fully susceptible to tenofovir (based on the genoarchive assay); baseline archived RAMs to tenofovir (4 D/C/F/TAF participants) and emtricitabine (35 D/C/F/ TAF participants, mainly 31 with M184I/V) were observed.…”

Week 96 subgroup analyses of the phase 3, randomized AMBER and EMERALD trials evaluating the efficacy and safety of the once daily darunavir/cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF) single-tablet regimen in antiretroviral treatment (ART)-naïve and -experienced, virologically-suppressed adults living with HIV-1

“…Patient baseline characteristics 14,18 of the 763 patients in the D/C/F/TAF treatment arm at baseline are shown in Supplementary Table 1…”

“…14 Antiviral efficacy was maintained through Week 96 in the D/C/F/TAF arms of both studies. 15,16 Pre-planned subgroup analyses demonstrated that D/ C/F/TAF was effective and well-tolerated through Week 48 regardless of demographic characteristics (age, gender, and race) in both studies, 17,18 clinical characteristics (baseline VL, CD4 þ cell count, and World Health Organization [WHO] clinical stage) in AMBER, 17 and prior ART experience in EMERALD. 18 The current paper reports the results of the same preplanned subgroup analyses cumulative through Week 96 in the D/C/F/TAF arms of each study.…”

Rates of adverse events of antiretroviral therapy in women living with HIV/AIDS: a systematic review and meta-analysis

“…Seven studies 2123 26 29 31 classified the gravity (grade) of AE using the DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (from the Division of AIDS of the US Department of Health and Human Services, National Institutes of Health, National Institute of Allergy and Infectious Diseases). The others did not describe which source they used for this classification.…”