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Good HIV Response Rate, Sustained Safety Through 96 Weeks With D/C/F/TAF
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HIV Drug Therapy, Glasgow 2018, October 28-31, 2018, Glasgow
Mark Mascolini
A single once-daily tablet combining darunavir, cobicistat, emtricitabine, and tenofovir alafenamide (D/C/F/TAF) maintained HIV suppression and good safety through 96 weeks of the randomized AMBER trial [1]. People who switched to D/C/F/TAF from D/C plus F/TDF at week 48 maintained similarly good virologic control and improved bone markers.
The European Union, the United States, and Canada have licensed D/C/F/TAF for antiretroviral-naive adults and certain treatment-experienced adults. AMBER is a phase 3 active-controlled double-blind trial that randomized antiretroviral-naive adults to D/C/F/TAF or D/C plus F/TDF for 48 weeks. At that point, 91% randomized to D/C/F/TAF and 88% randomized to the control regimen had a viral load below 50 copies, a result establishing the noninferiority of D/C/F/TAF [2]. After 48 weeks participants taking D/C plus F/TDF could switch to D/C/F/TAF and continue follow-up with the original D/C/F/TAF group through 96 weeks.
AMBER investigators initially randomized 362 people to D/C/F/TAF and 363 to the control regimen. Median age was 34 in both groups, 12% were women, 83% were white, and 18% had a viral load above 100,000 copies. Median pretreatment CD4 count stood at 453. After 96 weeks 85% initially randomized to D/C/F/TAF and 84% who switched from the control regimen had a viral load below 50 copies by FDA snapshot analysis. Respective proportions with a viral load at or above 50 copies were 5.5% and 4.4%. Virologic results proved consistent across participant subgroups.
From the start of the trial to week 96, the researchers counted 15 protocol-defined virologic failures in the D/C/F/TAF arm and 19 in the control arm. Among 17 people with virologic failure and resistance genotyping, no darunavir mutations, primary protease inhibitor mutations, or tenofovir mutations arose in either study arm. An M184V/I mutation evolved in 1 person in each study arm--at week 36 in the D/C/F/TAF group and at week 84 in the control group.
Through 48 weeks 8 people (2%) taking D/C/F/TAF had an adverse event leading to discontinuation. That number rose to 10 (3%) through 96 weeks. No one stopped D/C/F/TAF because of bone, kidney, or central nervous system adverse events. The researchers saw no clinically relevant changes in kidney function (eGFR) through 96 weeks in either study arm. Through 96 weeks people initially assigned to D/C/F/TAF had no change in hip bone mineral density (BMD) and a small drop in lumbar spine BMD. Over the same period in the switch group, there were small BMD increases at both hip and spine.
References
1. Orkin C, Eron JJ, Rockstroh J, et al. Efficacy and safety of the once-daily, darunavir/cobicistat/ emtricitabine/tenofovir alafenamide (D/C/F/TAF) single-tablet regimen (STR) in antiretroviral treatment (ART)-naive, HIV-1-infected adults: AMBER week 96 results. HIV Drug Therapy, Glasgow 2018, October 28-31, 2018, Glasgow. Abstract O212.
2. Eron JJ, Orkin C, Gallant J, et al. A week-48 randomized phase-3 trial of darunavir/cobicistat/emtricitabine/tenofovir alafenamide in treatment-naive HIV-1 patients. AIDS. 2018;32:1431-1442. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6039393/
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