Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2025
Doravirine/Islatravir (100/0.75 mg) Once-Daily Compared With Bictegravir/Emtricitabine/Tenofovir Alafenamide as Initial HIV-1 Treatment: 48-Week Results From a Phase 3, Randomized, Controlled, Double-Blind, Noninferiority Trial.
СтатьяКлиническое исследование III фазыРандомизированное исследованиеМногоцентровое исследованиеСравнительное исследованиеEquivalence TrialПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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Rockstroh Jürgen K, Paredes Roger, Cahn Pedro, Molina Jean-Michel, Sokhela Simiso M, Hinestrosa Federico, Kassim Sheetal, Cunningham Douglas, Ghosn Jade, Bogner Johannes R, Gatanaga Hiroyuki, Asante-Appiah Ernest, Zhang Ying, Nwoke Uchechukwu, Klopfer Stephanie O, Eves Karen, Squires Kathleen, Correll Todd, Fox Michelle C, Pisculli Mary L
Аннотация
BACKGROUND: Doravirine/islatravir is an investigational regimen that is being studied for human immunodeficiency virus type 1 (HIV-1) treatment.
METHODS: In this phase 3, double-blind, double-dummy trial (ClinicalTrials.gov NCT04233879), previously untreated adults with HIV-1 were randomized (1:1) and stratified by HIV-1 RNA (≤/>100 000 copies/mL) and CD4 count (</≥200 cells/µL) to doravirine/islatravir (100/0.75 mg) or bictegravir/emtricitabine/tenofovir alafenamide (50/200/25 mg) orally once-daily (primary endpoint: percentage of participants with HIV-1 RNA <50 copies/mL at week 48; US Food and Drug Administration snapshot, 10% noninferiority margin).
RESULTS: Overall, 597 participants were treated; enrollment stopped early due to decreases in CD4 and lymphocyte counts observed in other islatravir studies. Doravirine/islatravir was noninferior to bictegravir/emtricitabine/tenofovir alafenamide: 265 of 298 (88.9%) versus 264 of 299 (88.3%) had HIV-1 RNA <50 copies/mL (difference, 0.5%; 95% confidence interval [CI]: -4.7, 5.6). Mean change from baseline in CD4 count was +182 and +234 cells/µL (difference, -50; 95% CI: -79, -21) with doravirine/islatravir versus bictegravir/emtricitabine/tenofovir alafenamide. Mean change in lymphocyte count was 0.01 and 0.21 × 109/L (difference, -0.20; 95% CI: -0.30, -0.10). Adverse events (AEs) occurred in 90.6% and 87.3% of participants, with coronavirus disease 2019 being most common (14.1%, 16.4%). Treatment-related AEs were similar (28.9%, 25.8%). AEs that led to discontinuations were higher with doravirine/islatravir (8.7%, 3.7%) due to protocol-specified criteria that required discontinuation for decreased CD4 and lymphocyte counts.
CONCLUSIONS: Doravirine/islatravir (100/0.75 mg) once-daily was noninferior to bictegravir/emtricitabine/tenofovir alafenamide through week 48 for initial HIV-1 treatment. Due to decreases in CD4 and lymphocyte counts, development of this dose of doravirine/islatravir was stopped.
CLINICAL TRIALS REGISTRATION: NCT04233879.
METHODS: In this phase 3, double-blind, double-dummy trial (ClinicalTrials.gov NCT04233879), previously untreated adults with HIV-1 were randomized (1:1) and stratified by HIV-1 RNA (≤/>100 000 copies/mL) and CD4 count (</≥200 cells/µL) to doravirine/islatravir (100/0.75 mg) or bictegravir/emtricitabine/tenofovir alafenamide (50/200/25 mg) orally once-daily (primary endpoint: percentage of participants with HIV-1 RNA <50 copies/mL at week 48; US Food and Drug Administration snapshot, 10% noninferiority margin).
RESULTS: Overall, 597 participants were treated; enrollment stopped early due to decreases in CD4 and lymphocyte counts observed in other islatravir studies. Doravirine/islatravir was noninferior to bictegravir/emtricitabine/tenofovir alafenamide: 265 of 298 (88.9%) versus 264 of 299 (88.3%) had HIV-1 RNA <50 copies/mL (difference, 0.5%; 95% confidence interval [CI]: -4.7, 5.6). Mean change from baseline in CD4 count was +182 and +234 cells/µL (difference, -50; 95% CI: -79, -21) with doravirine/islatravir versus bictegravir/emtricitabine/tenofovir alafenamide. Mean change in lymphocyte count was 0.01 and 0.21 × 109/L (difference, -0.20; 95% CI: -0.30, -0.10). Adverse events (AEs) occurred in 90.6% and 87.3% of participants, with coronavirus disease 2019 being most common (14.1%, 16.4%). Treatment-related AEs were similar (28.9%, 25.8%). AEs that led to discontinuations were higher with doravirine/islatravir (8.7%, 3.7%) due to protocol-specified criteria that required discontinuation for decreased CD4 and lymphocyte counts.
CONCLUSIONS: Doravirine/islatravir (100/0.75 mg) once-daily was noninferior to bictegravir/emtricitabine/tenofovir alafenamide through week 48 for initial HIV-1 treatment. Due to decreases in CD4 and lymphocyte counts, development of this dose of doravirine/islatravir was stopped.
CLINICAL TRIALS REGISTRATION: NCT04233879.
Предметные рубрики MeSH
HumansHIV InfectionsPyridonesDouble-Blind MethodAdultMaleHIV-1FemaleEmtricitabineMiddle AgedTenofovirAnti-HIV AgentsTriazolesAlanineHeterocyclic Compounds, 4 or More RingsViral LoadCD4 Lymphocyte CountDrug CombinationsHeterocyclic Compounds, 3-RingAdeninePiperazinesTreatment OutcomeAmidesDeoxyadenosines