Early intervention with 3BNC117 and romidepsin at antiretroviral treatment initiation in people with HIV-1: a phase 1b/2a, randomized trial.
Early intervention with 3BNC117 and romidepsin at antiretroviral treatment initiation in people with HIV-1: a phase 1b/2a, randomized trial.
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HIV-1患者的抗逆转录病毒治疗启动时，使用3bnc117和romidepsin的早期干预：1b/2a期随机试验。
DOI：
10.1038/s41591-022-02023-7
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发表时间：
2022-11
期刊：
影响因子：
82.9
通讯作者：
Sogaard, Ole S.
中科院分区：
文献类型：
--
作者：
Gunst, Jesper D.;Pahus, Marie H.;Rosas-Umbert, Miriam;Lu, I-Na;Benfield, Thomas;Nielsen, Henrik;Johansen, Isik S.;Mohey, Rajesh;Ostergaard, Lars;Klastrup, Vibeke;Khan, Maryam;Schleimann, Mariane H.;Olesen, Rikke;Stovring, Henrik;Denton, Paul W.;Kinloch, Natalie N.;Copertino, Dennis C.;Ward, Adam R.;Alberto, Winiffer D. Conce;Nielsen, Silke D.;Puertas, Maria C.;Ramos, Victor;Reeves, Jacqueline D.;Petropoulos, Christos J.;Martinez-Picado, Javier;Brumme, Zabrina L.;Jones, R. Brad;Fox, Julie;Tolstrup, Martin;Nussenzweig, Michel C.;Caskey, Marina;Fidler, Sarah;Sogaard, Ole S.
Attempts to reduce the HIV-1 reservoir and induce antiretroviral therapy (ART)-free virological control have largely been unsuccessful. In this phase 1b/2a, open-label, randomized controlled trial using a 4-group factorial design, we investigated whether early intervention in newly diagnosed people with HIV-1 with a monoclonal anti-HIV-1-CD4 binding-site antibody, 3BNC117, followed by a histone deacetylase inhibitor, romidepsin, shortly after ART initiation altered the course of HIV-1 infection [NCT03041012]. The trial was undertaken in five hospitals in Denmark and two hospitals in the United Kingdom. The co-primary endpoints were analysis of initial virus decay kinetics and changes in the frequency of CD4+ T cells containing intact HIV-1 provirus from baseline to day 365. Secondary endpoints included changes in the frequency of infected CD4+ T cells and virus-specific CD8+ T cell immunity from baseline to day 365, pre-ART plasma HIV-1 3BNC117-sensitivity, safety and tolerability, and time to loss of virologic control during a 12-week analytical ART interruption that started at day 400. Among 55 newly diagnosed people (5 females and 50 males) with HIV-1 who received random allocation treatment, we found that early 3BNC117 treatment with or without romidepsin enhanced plasma HIV-1 RNA decay rates compared to ART only. Further, 3BNC117 treatment accelerated clearance of infected cells compared to ART only. All groups had significant reductions in the frequency of CD4+ T cells containing intact HIV-1 provirus. At day 365, early 3BNC117+romidepsin was associated with enhanced HIV-1 Gag-specific CD8+ T cell immunity compared to ART only. The observed virological and immunological effects of 3BNC117 were most pronounced in individuals whose pre-ART plasma HIV-1 envelope sequences were antibody-sensitive. The results were not disaggregated by sex. Adverse events were mild to moderate and similar between the groups. During a 12-week analytical ART interruption amongst 20 participants, 3BNC117-treated individuals harboring sensitive viruses were significantly more likely to maintain ART-free virologic control than other participants. We conclude that 3BNC117 at ART initiation enhanced elimination of plasma viruses and infected cells, enhanced HIV-1-specific CD8+ immunity and was associated with sustained ART-free virologic control among persons with 3BNC117-sensitive virus. These findings strongly support interventions administered at the time of ART initiation as a strategy to limit long-term HIV-1 persistence clinicaltrials.gov identifier: NCT03041012. The Danish Council for Independent Research (grants #7016-00022 and #9060-00023B), Central Region Denmark Research Fund, The Danish Regions’ Medicine and Treatment Fund, Aarhus University, and Next Experimental Therapy Partnership.
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影响因子：
3.7
作者：
Archin NM;Cheema M;Parker D;Wiegand A;Bosch RJ;Coffin JM;Eron J;Cohen M;Margolis DM
通讯作者：
Margolis DM
影响因子：
16.6
作者：
Dufloo J;Planchais C;Frémont S;Lorin V;Guivel-Benhassine F;Stefic K;Casartelli N;Echard A;Roingeard P;Mouquet H;Schwartz O;Bruel T
通讯作者：
Bruel T
DOI：
10.1016/j.cjca.2020.11.010
发表时间：
2021-09
期刊：
The Canadian journal of cardiology
影响因子：
--
作者：
Austin PC;White IR;Lee DS;van Buuren S
通讯作者：
van Buuren S
影响因子：
64.8
作者：
Caskey M;Klein F;Lorenzi JC;Seaman MS;West AP Jr;Buckley N;Kremer G;Nogueira L;Braunschweig M;Scheid JF;Horwitz JA;Shimeliovich I;Ben-Avraham S;Witmer-Pack M;Platten M;Lehmann C;Burke LA;Hawthorne T;Gorelick RJ;Walker BD;Keler T;Gulick RM;Fätkenheuer G;Schlesinger SJ;Nussenzweig MC
通讯作者：
Nussenzweig MC
影响因子：
6.4
作者：
Archin, Nancy M.;Bateson, Rosalie;Margolis, David M.
通讯作者：
Margolis, David M.