Once Daily Single-Tablet HIV Regimen Safe and Effective
Darunavir/cobicistat/emtricitabine/tenofovir alafenamide combines the efficacy and high genetic barrier to resistance of darunavir with the safety benefits of tenofovir alafenamide.
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SAN FRANCISCO — Once-daily single-tablet regimen of darunavir/cobicistat/emtricitabine/tenofovir alafenamide in adults who have achieved virologic suppression of HIV-1 infection has a high efficacy and safety profile similar to that of boosted-protease inhibitors plus emtricitabine/tenofovir disoproxil fumarate regimens, according to the results of a study on optimizing HIV treatment presented at IDWeek 2018, held October 3 to 7, 2018, in San Francisco, California.
HIV-related morbidity and mortality have declined significantly since the advent of combination antiretroviral therapy (ART). However, incomplete adherence to ART and the emergence of antiretroviral resistance can compromise the success of long-term treatment. Therefore, HIV-1 regimens that are simplified, with a reduced pill burden and fewer side-effects, are desirable for people living with HIV and might improve treatment adherence, satisfaction, and virologic outcomes. The darunavir/cobicistat/emtricitabine/tenofovir alafenamide regimen is the first and only single-tablet HIV-1 regimen in development that includes a protease inhibitor (darunavir). This regimen also combines the high genetic barrier to resistance of darunavir with the renal and bone safety advantages of tenofovir alafenamide in adults who have attained virologic suppression of HIV-1-infection, including those with a history of virologic failure on non-darunavir-based regimens.
The EMERALD study (ClinicalTrials.gov identifier: NCT02269917) has previously established that the once-daily single-tablet regimen darunavir/cobicistat/emtricitabine/tenofovir alafenamide (800/150/200/10 mg) was noninferior to boosted-protease inhibitors plus emtricitabine/tenofovir disoproxil fumarate regimens at 48 weeks. This study further examined the efficacy and safety of darunavir/cobicistat/emtricitabine/tenofovir alafenamide through week 96.
Individuals from the EMERALD trial who have been on ART and attained virologic suppression of HIV-1 infection with a viral load <50 copies/mL for ≥2 months were included as were patients with a history of virologic failure on non-darunavir regimens. Participants were randomly assigned (2:1) to switch to darunavir/cobicistat/emtricitabine/tenofovir alafenamide or continue boosted-protease inhibitors plus emtricitabine/tenofovir disoproxil fumarate over 48 weeks. Participants could then continue darunavir/cobicistat/emtricitabine/tenofovir alafenamide or switch from boosted-protease inhibitors plus emtricitabine/tenofovir disoproxil fumarate to the former regimen at week 52, which was considered “late switch” with a total of 44 weeks of darunavir/cobicistat/emtricitabine/tenofovir alafenamide exposure, in a single-arm extension phase until week 96. Of the 1141 total patients and treated patients, 1080 continued in the extension phase past 48 weeks (n=728 darunavir/cobicistat/emtricitabine/tenofovir alafenamide; n=352 late switch).
Switching to darunavir/cobicistat/emtricitabine/tenofovir alafenamide maintained high virologic suppression rates (>90%) at week 96 with no development of resistance. In addition, darunavir/cobicistat/emtricitabine/tenofovir alafenamide was well tolerated at >96 weeks, with bone, renal, and lipid safety consistent with known tenofovir alafenamide and cobicistat profiles. Only 3.1% of patients had virologic rebound cumulative through week 96 in the darunavir/cobicistat/emtricitabine/tenofovir alafenamide arm, whereas virologic rebound occurred in 2.3% in the late switch arm. Many of these rebounders had suppression again by week 96 (14/24 and 2/8, respectively). At week 96, 90.7% of patients in the darunavir/cobicistat/emtricitabine/tenofovir alafenamide arm and 93.8% in the late switch arm had viral suppression (viral load <50 copies/ mL). Few serious adverse events or treatment discontinuation because of adverse events occurred in either arm.
Overall, the study authors concluded, “Efficacy and safety results in the late switch arm were consistent with week 48 results in the darunavir/cobicistat/emtricitabine/tenofovir alafenamide arm. Darunavir/cobicistat/emtricitabine/tenofovir alafenamide combines the efficacy and high genetic barrier to resistance of darunavir with the safety benefits of tenofovir alafenamide, even in patients with a history of non-darunavir virologic failure.”
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Eron J Jr, Orkin C, Cunningham D, et al. 2018. Efficacy and safety of switching from boosted-protease inhibitors (bPI) plus emtricitabine/tenofovir disoproxil fumarate (F/TDF) regimens to the once daily (QD), single-tablet regime (STR) of darunavir/cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF) in virologically-suppressed, HIV-1-infected adults: week 96 results of the phase 3, randomized, non-inferiority EMERALD trial. Presented at: IDWeek 2018; October 3-7, 2018; San Francisco, CA. Poster 1768.