Analysis of Viral Blips Through Week 192 of the DRIVE-FORWARD and DRIVE-AHEAD Phase 3 Studies of Doravirine-Based Regimens in Adults Living With Previously Untreated HIV-1

Background We present a post hoc analysis of viral blips (HIV-1 RNA ≥50 copies/mL between 2 values of <50 copies/mL) in the DRIVE-FORWARD and DRIVE-AHEAD doravirine (DOR) Phase 3 studies. Methods Adults living with untreated HIV-1 were randomized (1:1) to a DOR-containing regimen or comparator (darunavir/ritonavir- or efavirenz-containing), each with 2 nucleos(t)ide reverse transcriptase inhibitors, for 96 weeks (double-blind base), followed by 96 weeks of a DOR-containing regimen (open-label extension). Cox proportional hazards models were used to analyze relationships between frequency of blips, baseline characteristics, and virologic rebound (2 consecutive HIV-1 RNA ≥50 copies/mL). Results In the base studies, blips occurred in 11.1%–11.9% of participants who received DOR and 12.1%–15.4% who received comparator. In the extensions, blips occurred in 5.5%–7.9% of participants. Baseline HIV-1 RNA ≤100 000 copies/mL was associated with lower likelihood of blips in the base studies (hazard ratio [HR], 0.41; [95% CI, 0.29–0.58]) and in participants who continued DOR in the extensions (0.41 [0.19–0.87]). Baseline CD4+ T-cell count ≤200 cells/mm3 was associated with increased likelihood of blips in participants who switched to DOR (3.47 [1.43–8.43]). Virologic rebound occurred in 7.0% of participants in the base studies and 3.8% in the extensions. Virologic rebound was more common in participants with blips versus no blips in the base studies (13.6% vs 6.1%; 3.79 [2.32–6.18]). Conclusions Blips were associated with increased risk of virologic rebound during the base study, and blips were less likely in participants with lower baseline HIV-1 RNA. Doravirine and comparator groups had similar rates of viral blips. Clinical Trials Registration. ClinicalTrials.gov NCT02275780, NCT02403674