HIV-1 resistance rarely observed in subjects using darunavir once-daily regimens across clinical studies

Abstract

Darunavir has a high genetic barrier to resistance. Across a diverse population of HIV-1-infected subjects treated with darunavir 800 mg QD regimens, the development of darunavir resistance was rare (<0.1%).

Bioequivalence of the Once‐Daily Single‐Tablet Regimen of Darunavir, Cobicistat, Emtricitabine, and Tenofovir Alafenamide Compared to Combined Intake of the Separate Agents and the Effect of Food on Bioavailability

“…Once‐daily boosted DRV 800 mg has demonstrated a high and durable virologic response in a range of patient populations and a high genetic barrier to the development of resistance . Current treatment guidelines include DRV/COBI combined with 2 nucleoside reverse transcriptase inhibitors, or administered as the D/C/F/TAF single‐tablet regimen, as a recommended treatment option for HIV‐1 treatment‐naive patients or recommended either when integrase inhibitors are not an option or in certain clinical situations…”

“…Once-daily boosted DRV 800 mg has demonstrated a high and durable virologic response in a range of patient populations and a high genetic barrier to the development of resistance. [10][11][12][13][14] Current treatment guidelines include DRV/COBI combined with 2 nucleoside reverse transcriptase inhibitors, or administered as the D/C/F/TAF single-tablet regimen, as a recommended treatment option for HIV-1 treatmentnaive patients 15,16 or recommended either when integrase inhibitors are not an option or in certain clinical situations. 17,18 TAF is a prodrug predominantly hydrolyzed to tenofovir intracellularly by cathepsin A5, resulting in higher intracellular levels of the active moiety tenofovir diphosphate and 90% lower plasma tenofovir concentrations relative to tenofovir disoproxil fumarate (TDF).…”

Impact of Splitting or Crushing on the Relative Bioavailability of the Darunavir/Cobicistat/Emtricitabine/Tenofovir Alafenamide Single‐Tablet Regimen

“…Darunavir, together with a PK enhancer (cobicistat or ritonavir) and 2 nucleos(t)ide reverse transcriptase inhibitors, is recommended as an initial ARV regimen in certain clinical situations per guidelines from the US Department of Health and Human Services; this regimen is also recommended in guidelines from the European AIDS Clinical Society . Darunavir has a high barrier to resistance that has been demonstrated in numerous studies and reconfirmed most recently in an analysis of 7 clinical trials . In this latest analysis of subjects treated with darunavir 800 mg once daily in studies with durations of up to 192 weeks, 0.2% of all subjects developed or had identified primary protease inhibitor and/or darunavir resistance‐associated mutations .…”

“…23,24 Darunavir has a high barrier to resistance that has been demonstrated in numerous studies and reconfirmed most recently in an analysis of 7 clinical trials. [7][8][9][10] In this latest analysis of subjects treated with darunavir 800 mg once daily in studies with durations of up to 192 weeks, 0.2% of all subjects developed or had identified primary protease inhibitor and/or darunavir resistance-associated mutations. 10 For patients who have suboptimal adherence, use of an ARV agent with a high barrier to resistance is a strategy that can be employed to lessen the likelihood of resistance development.…”

“…Darunavir/cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF; 800/150/200/10 mg) is an oral once‐daily single‐tablet regimen that is approved in Europe, Canada, and the United States. Studies of the protease inhibitor darunavir have demonstrated a durable virologic response, long‐term safety, and a high barrier to the development of resistance . Cobicistat acts as a pharmacokinetic boosting agent for darunavir by inhibition of drug metabolism .…”