Switching to Doravirine/Lamivudine/Tenofovir Disoproxil Fumarate (DOR/3TC/TDF) Maintains HIV-1 Virologic Suppression Through 48 Weeks: Results of the DRIVE-SHIFT Trial

Abstract

Doravirine is a novel, non-nucleoside reverse transcriptase inhibitor (NNRTI) with demonstrated efficacy in treatment-naïve adults with HIV-1. In this open-label, active-controlled, non-inferiority trial, adults with HIV-1 virologically suppressed for ≥6 months on 2 NRTIs plus a boosted protease inhibitor (PI), boosted elvitegravir, or an NNRTI were randomized (2:1) to switch to once-daily, single-tablet doravirine 100mg with lamivudine 300mg and tenofovir disoproxil fumarate 300mg (DOR/3TC/TDF) or to continue their current therapy (Baseline Regimen) for 24 weeks. The primary endpoint was the proportion of participants with HIV-1 RNA <50 copies/mL (FDA Snapshot approach), with the primary comparison between DOR/3TC/TDF at week 48 and Baseline Regimen at week 24, and a secondary comparison between the groups at week 24 (non-inferiority margin, -8%). 670 participants (447 DOR/3TC/TDF, 223 Baseline Regimen) were treated and included in the analyses. At week 24, 93.7% on DOR/3TC/TDF vs 94.6% on Baseline Regimen had HIV-1 RNA <50 copies/mL (difference -0.9 [-4.7, 3.0]). At week 48, 90.8% on DOR/3TC/TDF had HIV-1 RNA <50 copies/mL, demonstrating non-inferiority vs Baseline Regimen at week 24 (difference -3.8 [-7.9, 0.3]). In participants on ritonavir-boosted PI at entry, mean reductions in fasting LDL-C and non-HDL-C at week 24 were significantly greater for DOR/3TC/TDF vs Baseline Regimen (p<0.0001). Adverse events occurred in 68.9% on DOR/3TC/TDF and 52.5% on Baseline Regimen by week 24, leading to treatment discontinuation in 2.5% and 0.4%, respectively. Switching to once-daily DOR/3TC/TDF is a generally well-tolerated option for maintaining viral suppression in patients considering a change in therapy. ClinicalTrials.gov NCT02397096 This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.