Journal of acquired immune deficiency syndromes (1999) · 2026
Resistance Analysis of Weekly Islatravir Plus Lenacapavir in People With HIV at 48 Weeks.
СтатьяКлиническое исследование II фазыРандомизированное исследованиеНазвание и аннотация: Перевод в очереди
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VanderVeen Laurie A, Selzer Lisa, Chang Silvia, Li Jiani, Diamond Tracy L, Asante-Appiah Ernest, Llamoso Cyril, Rhee Martin S, Callebaut Christian
Аннотация
BACKGROUND: Islatravir (ISL), a nucleoside reverse transcriptase translocation inhibitor, and lenacapavir (LEN), a capsid inhibitor, have pharmacokinetic profiles supporting once-weekly (QW) oral dosing. In a phase 2 study, QW ISL + LEN maintained a high rate (94.2%) of viral suppression (VS; HIV-1 RNA <50 copies/mL) at week 48. We report resistance analyses through week 48.
METHODS: Virologically suppressed participants received ISL (2 mg QW) plus LEN (600 mg days 1 + 2, then 300 mg QW; n = 52) or once-daily bictegravir/emtricitabine/tenofovir alafenamide (50/200/25 mg; n = 52). Proviral DNA sequencing of HIV-1 protease, reverse transcriptase, and integrase was performed at screening; available historical genotypes were collected. Participants with primary nucleoside reverse transcriptase inhibitor (NRTI) or non-NRTI resistance-associated mutations were excluded. Postbaseline resistance analyses were performed for participants with HIV-1 RNA ≥200 copies/mL at virologic failure (≥50 copies/mL at 2 consecutive visits or ≥50 copies/mL at study drug discontinuation/last visit).
RESULTS: Of 104 enrolled participants, 5 randomized with historical genotypes were subsequently found to have primary NRTI and/or non-NRTI resistance-associated mutations: all 5 maintained VS, including 2 participants with M184V/I (1/group). One participant receiving ISL + LEN with low-level viremia on day 1 (HIV-1 RNA 251 copies/mL) met criteria for resistance analysis; no emergent resistance was observed, and they subsequently resuppressed on ISL + LEN. Longitudinal analysis of plasma virus detected identical viruses with no evidence of viral evolution.
CONCLUSIONS: ISL + LEN maintained high rates of VS, including in 1 participant with pre-existing M184V. No participants developed drug resistance. These findings support the ongoing evaluation of QW oral ISL + LEN for HIV-1 treatment.
METHODS: Virologically suppressed participants received ISL (2 mg QW) plus LEN (600 mg days 1 + 2, then 300 mg QW; n = 52) or once-daily bictegravir/emtricitabine/tenofovir alafenamide (50/200/25 mg; n = 52). Proviral DNA sequencing of HIV-1 protease, reverse transcriptase, and integrase was performed at screening; available historical genotypes were collected. Participants with primary nucleoside reverse transcriptase inhibitor (NRTI) or non-NRTI resistance-associated mutations were excluded. Postbaseline resistance analyses were performed for participants with HIV-1 RNA ≥200 copies/mL at virologic failure (≥50 copies/mL at 2 consecutive visits or ≥50 copies/mL at study drug discontinuation/last visit).
RESULTS: Of 104 enrolled participants, 5 randomized with historical genotypes were subsequently found to have primary NRTI and/or non-NRTI resistance-associated mutations: all 5 maintained VS, including 2 participants with M184V/I (1/group). One participant receiving ISL + LEN with low-level viremia on day 1 (HIV-1 RNA 251 copies/mL) met criteria for resistance analysis; no emergent resistance was observed, and they subsequently resuppressed on ISL + LEN. Longitudinal analysis of plasma virus detected identical viruses with no evidence of viral evolution.
CONCLUSIONS: ISL + LEN maintained high rates of VS, including in 1 participant with pre-existing M184V. No participants developed drug resistance. These findings support the ongoing evaluation of QW oral ISL + LEN for HIV-1 treatment.