Annals of internal medicine · 2025
Once-Weekly Oral Islatravir Plus Lenacapavir Versus Daily Oral Bictegravir, Emtricitabine, and Tenofovir Alafenamide in Persons With HIV-1 : A Phase 2 Randomized Study.
СтатьяРандомизированное исследованиеКлиническое исследование II фазыМногоцентровое исследованиеНазвание и аннотация: Перевод в очереди
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Colson Amy E, Crofoot Gordon E, Ruane Peter J, Ramgopal Moti N, Dretler Alexandra W, Nahass Ronald G, Sinclair Gary I, Berhe Mezgebe, Roberts Afsoon, Applin Shauna, Brinson Cynthia, Jayaweera Dushyantha, Workowski Kimberly A, Shihadeh Fadi, Liu Shan-Yu, Klopfer Stephanie, Llamoso Cyril, Madera Sharline, Dvory-Sobol Hadas, Rhee Martin S, Rhee Elizabeth G, Baeten Jared M, Eron Joseph J
Аннотация
BACKGROUND: Once-weekly oral islatravir plus lenacapavir (ISL+LEN) has the potential to address adherence challenges with daily HIV-1 treatment.
OBJECTIVE: To evaluate efficacy and safety of once-weekly ISL+LEN.
DESIGN: Phase 2, randomized, open-label, active-controlled study. (ClinialTrials.gov: NCT05052996).
SETTING: 44 U.S. sites.
PARTICIPANTS: Adults with HIV-1 RNA viral load of less than 50 copies/mL receiving daily bictegravir, emtricitabine, and tenofovir alafenamide combination (B/F/TAF) for 24 weeks or more.
INTERVENTION: Once-weekly oral ISL, 2 mg, plus LEN, 300 mg, or daily oral B/F/TAF.
MEASUREMENTS: Proportion with HIV-1 RNA viral load of 50 copies/mL or more at week 24 (primary end point; U.S. Food and Drug Administration Snapshot Algorithm). Secondary end points: proportion of participants with HIV-1 RNA viral load of 50 copies/mL or more (weeks 12 and 48) and HIV-1 RNA viral load of less than 50 copies/mL (weeks 12, 24. and 48), safety, and CD4+ T-cell and lymphocyte count changes (weeks 12, 24, and 48).
RESULTS: A total of 104 participants were randomly assigned and treated (n = 52 per group). At week 24, one ISL+LEN participant and no B/F/TAF participants had HIV-1 RNA viral load of 50 copies/mL or more (difference, 1.9% [95% CI, -5.2% to 10.5%]); 94.2% of participants in both groups had HIV-1 RNA viral load of less than 50 copies/mL (difference, 0% [CI, -10.9% to 10.9%]). At week 48, 94.2% and 92.3% of ISL+LEN and B/F/TAF participants, respectively, had HIV-1 RNA viral load of less than 50 copies/mL (difference, 1.9% [CI, -9.3% to 13.6%]); no participant had HIV-1 RNA viral load of 50 copies/mL or more. Two ISL+LEN participants discontinued treatment (before week 24) due to adverse events (AEs) unrelated to the study drug. No AEs that were grade 3 or greater or serious were related to treatment in either group. Changes in CD4+ T-cell and lymphocyte counts from baseline to week 48 were similar between groups, with no discontinuations of study drug treatment due to decreased CD4+ T cells or lymphocytes.
LIMITATION: Open-label, modest sample size, and only U.S.-based participants.
CONCLUSION: Once-weekly oral ISL+LEN maintained high rates of virologic suppression through week 48 and was not associated with any treatment-related grade 3 or greater or serious AEs.
PRIMARY FUNDING SOURCE: Gilead Sciences, Inc.
OBJECTIVE: To evaluate efficacy and safety of once-weekly ISL+LEN.
DESIGN: Phase 2, randomized, open-label, active-controlled study. (ClinialTrials.gov: NCT05052996).
SETTING: 44 U.S. sites.
PARTICIPANTS: Adults with HIV-1 RNA viral load of less than 50 copies/mL receiving daily bictegravir, emtricitabine, and tenofovir alafenamide combination (B/F/TAF) for 24 weeks or more.
INTERVENTION: Once-weekly oral ISL, 2 mg, plus LEN, 300 mg, or daily oral B/F/TAF.
MEASUREMENTS: Proportion with HIV-1 RNA viral load of 50 copies/mL or more at week 24 (primary end point; U.S. Food and Drug Administration Snapshot Algorithm). Secondary end points: proportion of participants with HIV-1 RNA viral load of 50 copies/mL or more (weeks 12 and 48) and HIV-1 RNA viral load of less than 50 copies/mL (weeks 12, 24. and 48), safety, and CD4+ T-cell and lymphocyte count changes (weeks 12, 24, and 48).
RESULTS: A total of 104 participants were randomly assigned and treated (n = 52 per group). At week 24, one ISL+LEN participant and no B/F/TAF participants had HIV-1 RNA viral load of 50 copies/mL or more (difference, 1.9% [95% CI, -5.2% to 10.5%]); 94.2% of participants in both groups had HIV-1 RNA viral load of less than 50 copies/mL (difference, 0% [CI, -10.9% to 10.9%]). At week 48, 94.2% and 92.3% of ISL+LEN and B/F/TAF participants, respectively, had HIV-1 RNA viral load of less than 50 copies/mL (difference, 1.9% [CI, -9.3% to 13.6%]); no participant had HIV-1 RNA viral load of 50 copies/mL or more. Two ISL+LEN participants discontinued treatment (before week 24) due to adverse events (AEs) unrelated to the study drug. No AEs that were grade 3 or greater or serious were related to treatment in either group. Changes in CD4+ T-cell and lymphocyte counts from baseline to week 48 were similar between groups, with no discontinuations of study drug treatment due to decreased CD4+ T cells or lymphocytes.
LIMITATION: Open-label, modest sample size, and only U.S.-based participants.
CONCLUSION: Once-weekly oral ISL+LEN maintained high rates of virologic suppression through week 48 and was not associated with any treatment-related grade 3 or greater or serious AEs.
PRIMARY FUNDING SOURCE: Gilead Sciences, Inc.
Предметные рубрики MeSH
HumansMaleFemaleHIV-1AdultViral LoadHIV InfectionsEmtricitabineMiddle AgedAnti-HIV AgentsTenofovirRNA, ViralQuinolonesAdenineDrug Administration ScheduleAdministration, OralDrug CombinationsHeterocyclic Compounds, 4 or More RingsCD4 Lymphocyte CountAlanineDrug Therapy, CombinationHeterocyclic Compounds, 3-RingPiperazinesIndazolesAcetamidesAmidesPyridones