卡博特韦用于预防顺性别男性和跨性别女性中的 HIV。
Cabotegravir for HIV Prevention in Cisgender Men and Transgender Women.
机构信息
From the Center for Clinical AIDS Research and Education, David Geffen School of Medicine, University of California, Los Angeles (R.J.L., R.M.K.), the Lundquist Institute at Harbor-UCLA Medical Center, Torrance (E.D.), the San Francisco Department of Public Health, San Francisco (H.S.), and Gilead Sciences, Foster City (J.F.R.) - all in California; the Fred Hutchinson Cancer Research Center, Seattle (D.D., B.H., L. Cottle, M.L., Z.W.); the Louisiana State University Health Sciences Center, New Orleans (M.E.C.); Instituto Nacional de Infectologia Evandro Chagas-Fiocruz, Rio de Janeiro (L. Coelho, B.G.), University of São Paulo (E.G.K.), and Centro de Referência e Treinamento DST-AIDS-SP (J.V.M.), São Paulo, and Hospital Nossa Senhora da Conceição, Porto Alegre (B.S.) - all in Brazil; Via Libre (R.C.), Universidad Nacional Mayor de San Marcos (J.A.G.-C.), and Asociacion Civil Impacta Salud y Educacion (P.G., J.V.H.), Lima, and Asociacion Civil Selva Amazonica, Iquitos (J.C.H.) - all in Peru; the Research Institute for Health Sciences, Chiang Mai University, Chiang Mai (S.C.), and the Institute of HIV Research and Innovation, Bangkok (N.P.) - both in Thailand; the Division of HIV-AIDS Prevention, Centers for Disease Control and Prevention (E.F.D.), the School of Medicine (C.F.K., C.R.), and Rollins School of Public Health (C.R.), Emory University - both in Atlanta; the Perelman School of Medicine, University of Pennsylvania, Philadelphia (I.F.), and Pennsylvania State University, State College (S.D.F.) - both in Pennsylvania; St. Jude Children's Research Hospital, Memphis, TN (A.H.G.); University of North Carolina at Chapel Hill, Chapel Hill (H.V.T., J.J.E., M.S.C.), FHI 360, Durham (A. Asmelash, M.B., C.B., J.L., N.D.S., K.G.-F., A.J., M.M.), and ViiV Healthcare, Research Triangle (K.Y.S., W.S., D.M., A.R.) - all in North Carolina; Hospital General de Agudos José María Ramos Mejia (M.H.L.) and Fundación Huésped (O.S.) - both in Buenos Aires; the Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa (K.M.); University of Alabama at Birmingham, Birmingham (E.T.O., J.M.); Rutgers New Jersey Medical School, Newark (S. Swaminathan); Weill Cornell Medicine, New York (R.M.G.); Johns Hopkins University, Baltimore (P.R., P.S., E.P.-M., M.M., C.H., T.T.B., S.H.E., J.S.); University of Colorado Anschutz Medical Campus, Aurora (P.A.); Massachusetts General Hospital, Boston (C.P.); University of Miami, Coral Gables, FL (S. Safren); the Office of AIDS Research (T.H.H.) and Division of AIDS, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD (K.S., A. Adeyeye).
出版信息
N Engl J Med. 2021 Aug 12;385(7):595-608. doi: 10.1056/NEJMoa2101016.
BACKGROUND
Safe and effective long-acting injectable agents for preexposure prophylaxis (PrEP) for human immunodeficiency virus (HIV) infection are needed to increase the options for preventing HIV infection.
METHODS
We conducted a randomized, double-blind, double-dummy, noninferiority trial to compare long-acting injectable cabotegravir (CAB-LA, an integrase strand-transfer inhibitor [INSTI]) at a dose of 600 mg, given intramuscularly every 8 weeks, with daily oral tenofovir disoproxil fumarate-emtricitabine (TDF-FTC) for the prevention of HIV infection in at-risk cisgender men who have sex with men (MSM) and in at-risk transgender women who have sex with men. Participants were randomly assigned (1:1) to receive one of the two regimens and were followed for 153 weeks. HIV testing and safety evaluations were performed. The primary end point was incident HIV infection.
RESULTS
The intention-to-treat population included 4566 participants who underwent randomization; 570 (12.5%) identified as transgender women, and the median age was 26 years (interquartile range, 22 to 32). The trial was stopped early for efficacy on review of the results of the first preplanned interim end-point analysis. Among 1698 participants from the United States, 845 (49.8%) identified as Black. Incident HIV infection occurred in 52 participants: 13 in the cabotegravir group (incidence, 0.41 per 100 person-years) and 39 in the TDF-FTC group (incidence, 1.22 per 100 person-years) (hazard ratio, 0.34; 95% confidence interval, 0.18 to 0.62). The effect was consistent across prespecified subgroups. Injection-site reactions were reported in 81.4% of the participants in the cabotegravir group and in 31.3% of those in the TDF-FTC group. In the participants in whom HIV infection was diagnosed after exposure to CAB-LA, INSTI resistance and delays in the detection of HIV infection were noted. No safety concerns were identified.
CONCLUSIONS
CAB-LA was superior to daily oral TDF-FTC in preventing HIV infection among MSM and transgender women. Strategies are needed to prevent INSTI resistance in cases of CAB-LA PrEP failure. (Funded by the National Institute of Allergy and Infectious Diseases and others; HPTN 083 ClinicalTrials.gov number, NCT02720094.).
背景
需要安全有效的长效注射型抗 HIV 感染暴露前预防（PrEP）药物，以增加预防 HIV 感染的选择。
方法
我们开展了一项随机、双盲、双模拟、非劣效性试验，比较了每 8 周肌内注射 600mg 长效注射型卡替拉韦（CAB-LA，整合酶链转移抑制剂[INSTI]）与每日口服替诺福韦艾拉酚胺富马酸替诺福韦酯（TDF-FTC）用于预防 HIV 感染的效果，试验对象为有感染 HIV 风险的男男性行为者（MSM）顺性别男性和有感染 HIV 风险的跨性别女性。参与者按 1:1 随机分配至两种方案组，并随访 153 周。进行 HIV 检测和安全性评估。主要终点为 HIV 感染事件。
结果
意向治疗人群包括 4566 名接受随机分组的参与者；570 名（12.5%）为跨性别女性，中位年龄为 26 岁（四分位距，22 岁至 32 岁）。根据第一次预先设定的中期终点分析结果审查，该试验因疗效提前终止。在美国的 1698 名参与者中，49.8%（845 名）为黑人。1698 名参与者中有 52 名发生 HIV 感染事件：卡替拉韦组 13 例（发病率为 0.41/100 人年），TDF-FTC 组 39 例（发病率为 1.22/100 人年）（风险比，0.34；95%置信区间，0.18 至 0.62）。该疗效在各预设亚组中一致。卡替拉韦组有 81.4%的参与者出现注射部位反应，TDF-FTC 组有 31.3%的参与者出现该反应。在接受 CAB-LA 暴露后发生 HIV 感染的参与者中，发现了整合酶抑制剂耐药和 HIV 感染检测延迟。未发现安全性问题。
结论
CAB-LA 预防 MSM 和跨性别女性 HIV 感染的效果优于每日口服 TDF-FTC。需要制定策略来预防 CAB-LA PrEP 失败情况下的整合酶抑制剂耐药。（由美国国立过敏和传染病研究所和其他机构资助；HPTN 083 临床试验.gov 编号，NCT02720094）。
Zotero 插件