Switching to Daily Doravirine/Islatravir (100/0.25 mg) Maintains Viral Suppression Through Week 48 Despite Baseline Non-Nucleoside Reverse Transcriptase Inhibitor Resistance-Associated Mutations or M184I/V in Proviral DNA.

backgroundDoravirine/islatravir (DOR/ISL) is a 2-drug, single-tablet regimen in clinical development for once-daily treatment of adults living with HIV-1. We examined the impact of baseline resistance-associated mutations (RAMs) in proviral DNA on the response to DOR/ISL (100/0.25 mg) in virologically suppressed participants in three phase 3 studies.

methodsSamples were collected pre-dose from participants in studies P051 (NCT05631093), P052 (NCT05630755), and P054 (NCT05766501) to evaluate RAMs in proviral DNA at baseline. The prevalence of baseline non-nucleoside reverse transcriptase inhibitor (NNRTI) RAMs and M184I/V, and their impact on virologic suppression (HIV-1 RNA <50 copies/mL) at week 48, as well as on types of viremia (confirmed HIV-1 RNA ≥200 copies/mL, low-level viremia, and transient viremia), was examined. Samples from participants with confirmed HIV-1 RNA ≥200 copies/mL or who discontinued from treatment with HIV-1 RNA ≥200 copies/mL were assessed for viral drug resistance.

resultsAmong 1227 participants who switched to DOR/ISL, 323 (26.3%) had baseline NNRTI RAMs and 70 (5.7%) had baseline M184I/V. At week 48, DOR/ISL maintained HIV-1 RNA <50 copies/mL in ≥88% of participants with and/or without NNRTI RAMs and/or M184I/V detected in proviral DNA at baseline. The percentage of participants in each viremia category was comparable with regard to the presence or absence of NNRTI RAMs and/or M184I/V. No treatment-emergent resistance to DOR or ISL was observed in the 7 participants who met criteria for postbaseline resistance testing.

conclusionsBaseline NNRTI RAMs and M184I/V in proviral DNA did not impact virologic outcomes through 48 weeks after switching to DOR/ISL (100/0.25 mg). CLINICAL TRIALS REGISTRATION: ClinicalTrials.gov: NCT05631093, NCT05630755, NCT05766501.