The Journal of infectious diseases · 2026
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.
Клиническое исследование III фазыСтатьяМногоцентровое исследованиеРандомизированное исследованиеНазвание и аннотация: Перевод в очереди
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Diamond Tracy L, Grandhi Anjana, Fuszard Monica, Xu Yayun, Nwoke Uchechukwu, Zhang Ying, Klopfer Stephanie O, Eves Karen, Benner Jaime, Li Mengchun, Greaves Wayne, Lahoulou Rima, Kim Jason, Fox Michelle C, Asante-Appiah Ernest
Аннотация
BACKGROUND: Doravirine/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.
METHODS: Samples 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.
RESULTS: Among 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.
CONCLUSIONS: Baseline 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.
METHODS: Samples 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.
RESULTS: Among 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.
CONCLUSIONS: Baseline 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.