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AMBER: Darunavir-based, single-tablet regimen suppresses HIV in treatment-naive patients
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A once-daily, single-tablet HIV regimen containing darunavir was noninferior to standard therapy in treatment-naive patients, according to phase 3 data from the AMBER trial.
“The 48-week AMBER study results further build on the growing clinical data set that demonstrates the safety and efficacy of darunavir in a once-daily, single-pill dosing regimen,” Joseph Eron, MD, professor of medicine and director of the Clinical Core at the University of North Carolina Center for AIDS Research, said in a press release.
For the AMBER trial, Eron and colleagues randomly assigned 725 ART-naive patients in a 1:1 ratio to receive the investigational regimen containing 800 mg of darunavir, 150 mg of cobicistat, 200 mg of emtricitabine and 10 mg of tenofovir alafenamide (D/C/F/TAF) or standard therapy with darunavir and cobicistat (D/C) plus emtricitabine and tenofovir disoproxil fumarate (F/TDF). The primary outcome was the proportion of patients with viral suppression at 48 weeks. The FDA established a noninferiority confidence interval of 10%.
According to data presented at the European AIDS Conference, 91.4% of patients who received D/C/F/TAF were virally suppressed at week 48 vs. 88.4% of patients in the control group (2.7% difference; 95% CI, –1.6% to 7.1%). Virologic failure occurred in 4.4% in the D/C/F/TAF arm and 3.3% of patients in the control arm.
D/C/F/TAF was associated with more favorable bone and renal safety parameters, Eron and colleagues reported. Differences favoring D/C/F/TAF were observed in spine (–0.7% vs. –2.4%; P = .004) and hip (0.2% vs. –2.7%; P < .0001) bone mineral density, as well as quantitative measures of proteinuria, which was determined by changes in ratios of total urinary protein (–22.42 mg/g vs. –10.34 mg/g; P = .033), albumin (–2.45 mg/g vs. –0.58 mg/g; P = .003), retinol binding protein (16.84 g/g vs. 401.12 g/g; P < .0001) and beta2-microglobulin (–100.58 g/g vs. 837.63 g/g; P < .0001) to urine creatinine.
There were no significant differences in treatment discontinuations due to adverse events (1.9% vs. 4.4%), grade 3 or 4 adverse events (5.2% vs. 6.1%) and serious adverse events (4.7% vs. 5.8%) in the D/C/F/TAF and control arms. The most common adverse events included diarrhea (9% vs. 11%), rash (6% vs. 4%) and nausea (6% vs. 10%). No deaths occurred, and there was no resistance to any of the study drugs, the researchers said.
D/C/F/TAF was also evaluated in virally suppressed patients enrolled in the phase 3 EMERALD trial. Data presented at IDWeek showed similar rates of viral suppression among patients who switched to D/C/F/TAF and those who continued treatment with a boosted protease inhibitor plus F/TDF.
D/C/F/TAF is currently undergoing regulatory review for use in adults and children aged 12 years and older in the United States. The regimen was approved in Europe on Sept. 25 and is available under the brand name Symtuza.
If approved in the U.S., Rick Nettles, MD, vice president of medical affairs at Janssen Infectious Diseases, told Infectious Disease News that the single-tablet D/C/F/TAF regimen may improve treatment compliance among patients with HIV.
“Not taking HIV medication daily or missing doses can lead to medication resistance. While great progress has been made in HIV treatment during the past decade, there are still adherence challenges that remain, such as stigma, lifestyle and pill burden,” he said. “The 48-week AMBER results bring us one step closer to being able to offer those who live with HIV and struggle with adherence an option that combines the efficacy and high genetic barrier to resistance of darunavir with the safety profile of TAF in a single tablet.”
Janssen and its affiliates hold rights to manufacture, register, distribute and commercialize D/C/F/TAF as a single-tablet regimen worldwide through a licensing agreement between Janssen and Gilead Sciences.
Darunavir is sold under the brand name Prezista (Janssen). Cobicistat is sold under the brand name Tybost (Gilead Sciences). TAF is sold under the brand name Vemlidy (Gilead Sciences). D/C is sold under the brand name Prezcobix (Janssen). F/TDF is sold under the brand name Truvada (Gilead Sciences). – by Stephanie Viguers
Reference:
Gallant J, et al. Abstract PS8/2. Presented at: 16th European AIDS Conference; Oct. 25-27, 2017; Milan, Italy.
Orkin C, et al. Abstract 1689b. Presented at: IDWeek; Oct. 4-8, 2017; San Diego.
Orkin C, et al. Lancet HIV. 2017;doi:10.1016/S2352-3018(17)30179-0.
Disclosures: Eron reports being a consultant and grant investigator for Janssen. Nettles is an employee of Janssen.