HIV incidence among women using intramuscular depot medroxyprogesterone acetate, a copper intrauterine device, or a levonorgestrel implant for contraception: a randomised, multicentre, open-label trial-猫眼课题宝

DOI：

10.1016/s0140-6736(19)31288-7

发表时间：

2019-07-27

期刊：

LANCET

影响因子：

168.9

通讯作者：

中科院分区：

医学1区

文献类型：

作者：

Baeten, Jared M.;Donnell, Deborah;Stringer, Jeffrey

背景观察和实验室研究表明，一些激素避孕方法，特别是肌肉注射醋酸甲羟孕酮（DMPA-IM），可能会增加妇女对艾滋病毒感染的易感性。我们的目的是比较DMPA-IM，铜宫内节育器（IUD），左炔诺孕酮（LNG）植入寻求有效的避孕和生活在艾滋病高发区的非洲妇女。方法我们做了一个随机，多中心，开放标签试验，在12个研究地点在斯威士兰，肯尼亚，南非和赞比亚。我们纳入了16-35岁的HIV血清阴性女性，这些女性正在寻求有效的避孕措施，对试验避孕方法没有医学禁忌症，同意使用指定的方法18个月，并且报告在过去6个月内没有使用注射，宫内或植入式避孕措施。参与者被随机分配（1：1：1）接受每3个月注射150 mg/mL DMPA-IM，铜IUD或LNG植入物，随机区组大小在15至30之间，按部位分层。使用在线随机化系统分配受试者，每个研究中心的研究工作人员在每次随机化时访问该系统。主要终点是改良意向治疗人群中的HIV感染事件，包括入组时HIV阴性且至少进行了一次HIV检测的所有随机化受试者。主要安全性终点是任何严重不良事件或导致方法中止的任何不良事件，直至18个月时的试验退出访视，并在所有入组和随机分配的女性中进行评估。本研究已在ClinicalTrials注册。在2015年12月14日至2017年9月12日期间，7830名女性入组，7829名随机分配到DMPA-IM组（n=2609），铜IUD组（n=2607）或LNG植入组（n=2613）。7715名（99%）参与者被纳入改良的意向治疗人群（DMPA-IM组2556名，铜IUD组2571名，LNG植入组2588名），在10409名女性-年的随访时间中，9567名（92%）女性使用了指定的方法。397例艾滋病毒感染（发生率3.81/100女性-年[95% CI 3.45-4.21]）：143（36%; 4.19/100女性-年[3.54-4.94]），DMPA-IM组，138（35%：3.94/100女性-年[3.31-4.66]），LNG植入组116例（29%; 3.31/100女性-年[2.74-3.98]）。在改良的意向治疗分析中，HIV感染的风险比为1.04（96% CI 0.82-1.33，p= 0.72）DMPA-IM与铜IUD相比，1.23 DMPA-IM与LNG植入物相比为0.95-1.59，p= 0.097，铜IUD与LNG植入物相比为1.18（0.91-1.53，p=0.19）。研究期间有12名女性死亡：DMPA-IM组6名，铜IUD组5名，LNG植入组1名。DMPA-IM组2609名参与者中有49名（2%）发生严重不良事件，铜IUD组2607名参与者中有92名（4%），LNG植入组2613名参与者中有78名（3%）发生严重不良事件。DMPA-IM组109例（4%）、铜IUD组218例（8%）和LNG植入组226例（9%）发生了导致随机分配方法中止的不良事件（p

Background Observational and laboratory studies suggest that some hormonal contraceptive methods, particularly intramuscular depot medroxyprogesterone acetate (DMPA-IM), might increase women's susceptibility to HIV acquisition. We aimed to compare DMPA-IM, a copper intrauterine device (IUD), and a levonorgestrel (LNG) implant among African women seeking effective contraception and living in areas of high HIV incidence.Methods We did a randomised, multicentre, open-label trial across 12 research sites in eSwatini, Kenya, South Africa, and Zambia. We included HIV-seronegative women aged 16-35 years who were seeking effective contraception, had no medical contraindications to the trial contraceptive methods, agreed to use the assigned method for 18 months, and reported not using injectable, intrauterine, or implantable contraception for the previous 6 months. Participants were randomly assigned (1:1:1) to receive an injection of 150 mg/mL DMPA-IM every 3 months, a copper IUD, or a LNG implant with random block sizes between 15 and 30, stratified by site. Participants were assigned using an online randomisation system, which was accessed for each randomisation by study staff at each site. The primary endpoint was incident HIV infection in the modified intention-to-treat population, including all randomised participants who were HIV negative at enrolment and who contributed at least one HIV test. The primary safety endpoint was any serious adverse event or any adverse event resulting in method discontinuation, until the trial exit visit at 18 months and was assessed in all enrolled and randomly assigned women. This study is registered with ClinicalTrials. gov, number NCT02550067.Findings Between Dec 14, 2015, and Sept 12, 2017, 7830 women were enrolled and 7829 were randomly assigned to the DMPA-IM group (n=2609), the copper IUD group (n=2607), or the LNG implant group (n=2613). 7715 (99%) participants were included in the modified intention-to-treat population (2556 in the DMPA-IM group, 2571 in the copper IUD group, and 2588 in the LNG implant group), and women used their assigned method for 9567 (92%) of 10 409 woman-years of follow-up time. 397 HIV infections occurred (incidence 3.81 per 100 woman-years [95% CI 3.45-4.21]): 143 (36%; 4.19 per 100 woman-years [3.54-4.94]) in the DMPA-IM group, 138 (35%: 3.94 per 100 woman-years [3.31-4.66]) in the copper IUD group, and 116 (29%; 3.31 per 100 woman-years [2.74-3.98]) in the LNG implant group. In the modified intention-to-treat analysis, the hazard ratios for HIV acquisition were 1.04 (96% CI 0.82-1.33, p= 0.72) for DMPA-IM compared with copper IUD, 1.23 (0.95-1.59, p= 0.097) for DMPA-IM compared with LNG implant, and 1.18 (0.91-1.53, p=0.19) for copper IUD compared with LNG implant. 12 women died during the study: six in the DMPA-IM group, five in the copper IUD group, and one in the LNG implant group. Serious adverse events occurred in 49 (2%) of 2609 participants in the DMPA-IM group, 92 (4%) of 2607 participants in the copper IUD group, and 78 (3%) of 2613 participants in the LNG implant group. Adverse events resulting in discontinuation of the randomly assigned method occurred in 109 (4%) women in the DMPA-IM group, 218 (8%) women in the copper IUD group, and 226 (9%) women in the LNG implant group (p

HIV incidence among women using intramuscular depot medroxyprogesterone acetate, a copper intrauterine device, or a levonorgestrel implant for contraception: a randomised, multicentre, open-label trial

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