Once Daily Single-Tablet HIV Regimen Safe and Effective
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SAN FRANCISCO — Once-daily single-tablet regimen of darunavir/cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF) in adults who have achieved HIV-1 virologic suppression, has a similar efficacy and safety profile of boosted-protease inhibitors plus emtricitabine/tenofovir disoproxil fumarate (F/TDF), according to the results of a study 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. The D/C/F/TAF regimen is the first and only single-tablet HIV-1 regimen in development that includes a protease inhibitor (darunavir).
The EMERALD study (ClinicalTrials.gov identifier: NCT02269917) has previously established that the once-daily single-tablet regimen D/C/F/TAF (800/150/200/10 mg) was noninferior to boosted-protease inhibitors plus F/TDF regimens at 48 weeks. This study further examined the efficacy and safety of the regimen 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 and patients with a history of virologic failure on non-darunavir regimens were included. They were randomly assigned (2:1) to switch to D/C/F/TAF or continue boosted-protease inhibitors plus F/TDF over 48 weeks. Participants could then continue D/C/F/TAF or switch from boosted-protease inhibitors plus F/TDF to the former regimen at week 52, 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 D/C/F/TAF; n=352 late switch).
Switching to D/C/F/TAF was found to maintain high virologic suppression rates (>90%) at week 96 with no development of resistance. The regimen was also 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 D/C/F/TAF 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 D/C/F/TAF 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 D/C/F/TAF arm. D/C/F/TAF 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.