LB2. Switch to Doravirine/Lamivudine/Tenofovir Disoproxil Fumarate (DOR/3TC/TDF) Maintains Virologic Suppression Through 48 Weeks: Results of the DRIVE-SHIFT Trial

Abstract

Background. Doravirine is a novel, non‐nucleoside reverse‐transcriptase inhibitor (NNRTI) that has demonstrated efficacy in two Phase 3 trials in treatment‐naïve adults with HIV‐1. Methods. Tis open‐label, active‐controlled, noninferiority (NI) trial evaluated a once‐daily single‐tablet regimen of doravirine 100 mg, lamivudine 300 mg, and teno‐fovir disoproxil fumarate 300 mg (DOR/3TC/TDF) vs. continuation of current therapy in adults with HIV‐1 virologically suppressed for ≥6 months on a stable regimen of two NRTIs plus a boosted protease inhibitor (PI), boosted elvitegravir, or NNRTI. Participants with screening HIV‐1 RNA <40 copies/mL, no history of virologic failure on any regimen, and no resistance to DOR/3TC/TDF were randomized (2:1) to start DOR/3TC/TDF on Day 1 (immediate switch group, ISG) or afer 24 weeks (delayed switch group, DSG). The primary endpoint was the proportion (%) of participants with HIV‐1 RNA <50 copies/mL (FDA snapshot approach), with the primary comparison between ISG at Week 48 and DSG at Week 24 and a secondary comparison between the groups at Week 24; the NI margin was ‐8%. The % of participants with HIV‐1 RNA ≥50 copies/mL was also analyzed (FDA snapshot approach; NI margin 4%). Results. A total of 670 participants (447 ISG, 223 DSG) were treated and included in the analyses; 84.5% were male, 76.4% were white, and mean age was 43.3 years. At Week 24, 93.7% (419/447) of ISG vs. 94.6% (211/223) of DSG had HIV‐1 RNA <50 copies/mL (difer‐ence ‐0.9% [‐4.7, 3.0]), and 1.8% of each group had HIV‐1 RNA ≥50 copies/mL. At Week 48, 90.8% (406/447) of ISG maintained HIV‐1 RNA <50 copies/mL (vs. 94.6% of DSG at Week 24; diference ‐3.8%, 95% CI [‐7.9%, 0.3%]), and 1.6% of ISG had HIV‐1 RNA ≥50 copies/mL. In the ritonavir‐boosted PI stratum, mean changes in fasting LDL‐C and non‐HDL‐C at Week 24 were signifcantly lower (P < 0.0001) in ISG vs. DSG (table). Rates of any AE and of drug‐related AEs at Week 24 were higher in ISG vs. DSG. AEs were mild in most ISG participants (64% of those with any AE; 80% of those with drug‐related AEs). Conclusion. A once‐daily single‐tablet regimen of DOR/3TC/TDF demonstrated non‐inferior efficacy and acceptable safety compared with continuing therapy, and is an option for maintaining viral suppression in patients considering a change in therapy.