Darunavir-Cobicistat-Tenofovir alafenamide-Emtricitabine  Investigational

The fixed-dose combination tablet darunavir-cobicistat-tenofovir alafenamide-emtricitabine is an investigational single-tablet regimen. In clinical trials, investigators are comparing this single-tablet regimen to boosted protease inhibitors plus tenofovir DF-emtricitabine. If the single-tablet regimen proves to be safe and effective, it will offer a one pill daily regimen with high barrier to resistance (due to the darunavir-cobicistat), with potentially less renal and bone toxicity as compared to regimens that include tenofovir DF; it will, however, still have potential gastrointestinal adverse effects and drug interactions secondary to the cobicistat component. Further investigation into the safety and efficacy of this single-tablet regimen is needed.

Darunavir-cobicistat-tenofovir alafenamide-emtricitabine-tenofovir alafenamide is an investigational single-tablet antiretroviral regimen and therefore not included in the HHS Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents.

In a phase 2, randomized, double-blind, placebo-controlled trial, investigators enrolled 153 treatment-naïve individuals and randomized 103 to darunavir-cobicistat-tenofovir alafenamide-emtricitabine and 53 to darunavir-cobicistat plus tenofovir disoproxil fumarate-emtricitabine []. After 48 weeks, the proportion with HIV RNA below 50 copies/mL by FDA snapshot analysis was 76.7% in the darunavir-cobicistat-tenofovir alafenamide-emtricitabine arm and 84% in the darunavir-cobicistat plus tenofovir disoproxil fumarate-emtricitabine arm (a nonsignificant difference, demonstrating non-inferiority of the single-tablet tenofovir alafenamide regimen). Similar to other tenofovir alafenamide trials, participants in the tenofovir alafenamide arm of this trial experienced less decrease in bone mineral density over time and less renal tubular proteinuria, but greater increases in serum cholesterol parameters. A phase 3 trial in treatment-naïve patients is comparing the fixed dose single-tablet regimen darunavir-cobicistat-tenofovir alafenamide-emtricitabine with the regimen darunavir-cobicistat plus tenofovir DF-emtricitabine []. An ongoing study is assessing the efficacy of switching from a boosted protease inhibitor-anchored regimen to darunavir-cobicistat-tenofovir alafenamide-emtricitabine versus remaining on the boosted protease-inhibitor based regimen [].