Abstract
Background
DRV has demonstrated high efficacy and barrier to resistance development across diverse populations, from TN to heavily TE patients. We evaluated resistance data from 10 clinical studies of different DRV 800 mg QD–based antiretroviral regimens and formulations.
Methods
The analysis included patients from 10 phase 2/3 studies (48–192 weeks in duration) of ritonavir- and cobicistat-boosted DRV 800 mg QD–based regimens in TN and virologically failing or suppressed TE patients with HIV-1 (table). Three were phase 3 studies of the DRV/cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF) 800/150/200/10 mg single-tablet regimen (STR). Post-baseline resistance was evaluated in patients experiencing protocol-defined virologic failure (PDVF); definitions and criteria for resistance testing varied slightly among studies. Resistance-associated mutations (RAMs) were based on respective International Antiviral Society–USA mutation lists over time.
Results
Of the 3,635 patients evaluated, 250 met PDVF criteria and 205 had post-baseline genotypes/phenotypes. Overall, 4 (0.1%) patients developed (or had identified [switch studies]) ≥1 DRV and/or primary protease inhibitor (PI) RAM (table), and only 1 (< 0.1%, ODIN) patient lost DRV phenotypic susceptibility; this TE patient had prior VF with lopinavir. Among those who used a nucleos(t)ide reverse transcriptase inhibitor (NRTI) backbone (mostly emtricitabine [FTC] + tenofovir [TFV]), 12 (0.4%) patients had ≥1 NRTI RAM, including 10 with M184I/V associated with FTC resistance. No TFV RAMs were observed. Among patients receiving D/C/F/TAF (n = 1,949), none had post-baseline DRV, primary PI, or TFV RAMs; only 2 (0.1%) patients developed an FTC RAM.
Conclusion
Across a large, diverse population using DRV 800 mg QD–based regimens and formulations, resistance development remains rare; 0.1% of patients had ≥1 DRV and/or primary PI RAM post-baseline. Among 3 trials of the D/C/F/TAF STR, no patients developed a DRV or primary PI RAM. After > 10 years of investigating DRV 800 mg QD–based regimens in clinical trials, loss of phenotypic susceptibility to DRV has never been observed in TN or TE virologically suppressed patients and was only once observed in a TE patient with prior VF on multiple antiretrovirals, including a PI.
Disclosures
All authors: No reported disclosures.
Week 96 results of a phase 3 trial of darunavir/cobicistat/emtricitabine/tenofovir alafenamide in treatment-naive HIV-1 patients