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

Background: Doravirine is a novel, nonnucleoside reverse transcriptase inhibitor with demonstrated efficacy in treatment-naive adults with HIV-1.

Methods: In this open-label, active-controlled, noninferiority trial, adults with HIV-1 virologically suppressed for ≥6 months on 2 nucleoside reverse transcriptase inhibitors plus a boosted protease inhibitor, boosted elvitegravir, or a non-nucleoside reverse transcriptase inhibitor were randomized (2:1) to switch to once-daily, single-tablet doravirine 100 mg with lamivudine 300 mg and tenofovir disoproxil fumarate 300 mg (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 (defined by the 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 (noninferiority margin, -8%).

Results: Six hundred seventy 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 to 3.0)]. At week 48, 90.8% on DOR/3TC/TDF had HIV-1 RNA <50 copies/mL, demonstrating noninferiority vs Baseline Regimen at week 24 [difference -3.8 (-7.9 to 0.3)]. In participants on ritonavir-boosted protease inhibitor 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.

Conclusions: Switching to once-daily DOR/3TC/TDF is a generally well-tolerated option for maintaining viral suppression in patients considering a change in therapy.

Registration: ClinicalTrials.gov NCT02397096.

FIGURE 1.

Trial profile. DOR/3TC/TDF, doravirine/lamivudine/tenofovir disoproxil fumarate. Baseline Regimen = 2 NRTIs with a boosted PI, boosted elvitegravir, or an NNRTI. Percentages are based on the number of participants randomized (450 to ISG and 223 to DSG).

FIGURE 2.

Virologic outcomes (the FDA Snapshot approach). DOR/3TC/TDF, doravirine/lamivudine/tenofovir disoproxil fumarate. Baseline Regimen = 2 NRTIs with a boosted PI, boosted elvitegravir, or an NNRTI.

FIGURE 3.

Proportion of participants with HIV-1 RNA <50 copies/mL at week 24 (the FDA Snapshot approach) by prognostic factors (A) and demographic factors (B).

FIGURE 4.

Mean change from baseline in fasting lipid levels at week 24, in participants receiving a ritonavir-boosted PI regimen at study entry. DOR/3TC/TDF, doravirine/lamivudine/tenofovir disoproxil fumarate. ISG (N = 266). DSG (N = 133). Baseline Regimen = ritonavir-boosted PI with 2 NRTIs.