With over 36.7 million individuals around the world living with HIV, and more strains developing resistance to available treatment, researchers have been channeling their efforts into exploring the safety and efficacy of different combination antiretroviral regimens to keep the virus in check.
In a poster presentation
at the 25th Conference on Retroviruses and Opportunistic Infections
, Bruce Rashbaum, MD, Capital Medical Associates, shared week 48 results from the recent AMBER trial which explored the efficacy of the oral, once-daily, single-tablet regimen darunavir/cobicistat/emtricitabine/tenofovir alfenamide (D/C/F/TAF) in treatment naïve patients.
D/C/F/TAF is currently under regulatory review in the United States, although it has already been approved in Europe for the treatment of HIV-1 infection; it is the only single-tablet regimen in development for HIV-1 infection that contains darunavir (DRV) and F/TAF.
“Studies of DRV have demonstrated a durable virologic response, long-term safety, and high barrier to the development of resistance,” authors write. “The tenofovir prodrug TAF has shown similar efficacy and improved renal and bone safety compared with tenofovir disoproxil fumarate (TDF).”
Meanwhile, D/C/F/TAF has been evaluated in 2 pivotal phase 3 trials: EMERALD and AMBER. In the randomized (2:1), non-inferiority EMERALD trial
, investigators assessed the efficacy and safety of switching to D/C/F/TAF 800/150/200/10 mg vs continuing use of a boosted protease inhibitor +emtricitabine/tenofovir disoproxil fumarate (control). In a recent interview, Contagion ®
spoke with Gregory D. Huhn, MD, an infectious disease specialist in the Cook County Health System on what made the trial unique and its outcomes.
AMBER, on the other hand, assessed the efficacy and safety of D/C/F/TAF 800/150/200/10 mg vs control D/C+F/tenofovir disoproxil fumarate in ART-naïve adults infected with HIV-1 across subgroups based on age, gender, and race. In the randomized (1:1), noninferiority AMBER trial, the primary endpoint “was proportion of patients with virologic response (viral load [VL] <50 copies [c]/mL; FDA snapshot) at Week 48,” authors write. The trial included patients with baseline resistance-associated mutations to agents other than D, F, or TDF.
For the trial, a total of 725 patients were randomized and treated; according to the abstract, of the 725 participants, 68 were over 50 years of age, 85 were women, and 80 were of African American descent. Virologic response rates were, overall, 91.4% for D/C/F/TAF and 88.4% for control. Additionally, the researchers found that across race, gender, and age subgroups, response rates with the regimen were similar.
For the trial, safety was evaluated by adverse event rates, as well as changes in bone mineral density and renal (eGFR) from baseline to Week 48. In the total population, both arms of the study (control and D/C/F/TAF) showed similar rates of discontinuation due to an adverse event (4.4% and 1.9%), worst grade 3-4 adverse events (6.1% and 5.2%) and serious adverse events (5.8% and 4.7%). The authors did not note any differences across subgroups that were clinically relevant, however, those in the D/C/F/TAF arm were found to have experienced less adverse events. Furthermore, improvements in bone and renal safety parameters were observed in the D/C/F/TAF arm compared with the control arm across all subgroups.
“D/C/F/TAF achieved high virologic response rates that were overall non-inferior to control as well as favorable bone and renal outcomes,” the study authors concluded, “and demonstrated consistent results across subgroups by age, gender, and race through 48 weeks in ART-naïve, HIV-1 infected patients.”
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