Background

Women with HIV face an increased risk of preterm birth. 17 alpha-hydroxyprogesterone caproate (17P) has been shown in some trials to reduce early delivery among women with a history of spontaneous preterm birth. We investigated whether 17P would reduce this risk among women with HIV.

Methods

We did a randomised, double-blind, placebo-controlled trial in pregnant women with HIV at the University Teaching Hospital and Kamwala District Health Centre in Lusaka, Zambia. Eligible patients were women aged 18 years or older with confirmed HIV-1 infection, viable intrauterine singleton pregnancy at less than 24 weeks of gestation, and were receiving or intending to commence antiretroviral therapy during pregnancy. Exclusion criteria were major uterine or fetal anomaly; planned or in situ cervical cerclage; evidence of threatened miscarriage, preterm labour, or ruptured membranes at screening; medical contraindication to 17P; previous participation in the trial; or history of spontaneous preterm birth. Eligible participants provided written informed consent and were randomly assigned (1:1) to receive 250 mg intramuscular 17P or placebo once per week, starting between 16 and 24 weeks of gestation until delivery, stillbirth, or reaching term (37 weeks). Participants and study staff were masked to assignment, except for pharmacy staff who did random assignment and prepared injections but did not interact with participants. The primary outcome was a composite of delivery before 37 weeks or stillbirth at any gestational age. Patients attended weekly visits for study drug injections and antenatal care. We estimated the absolute and relative difference in risk of the primary outcome and safety events between treatment groups by intention to treat. This trial is registered with ClinicalTrials.gov, NCT03297216, and is complete.

Findings

Between Feb 7, 2018 and Jan 13, 2020, we assessed 1042 women for inclusion into the study. 242 women were excluded after additional assessments, and 800 eligible patients were enrolled and randomly assigned to receive intramuscular 17P (n=399) or placebo (n=401). Baseline characteristics were similar between groups. Adherence to study drug injections was 98% in both groups, no patients were lost to follow-up, and the final post-partum visit was on Aug 6, 2020. 36 (9%) of 399 participants assigned to 17P had preterm birth or stillbirth, compared with 36 (9%) of 401 patients assigned to placebo (risk difference 0·1, 95% CI −3·9 to 4·0; relative risk 1·0, 95% CI 0·6 to 1·6; p=0·98). Intervention-related adverse events were reported by 140 (18%) of 800 participants and occurred in similar proportions in both randomisation groups. No serious adverse events were reported.

Interpretation

Although 17P seems to be safe and acceptable to participants, available data do not support the use of the drug to prevent preterm birth among women whose risk derives solely from HIV infection. The low risk of preterm birth in both randomisation groups warrants further investigation.

Funding

US National Institutes of Health and the Bill and Melinda Gates Foundation.

中文翻译：

---

每周 17 次 α-羟基黄体酮己酸酯可预防 HIV 感染女性早产：一项随机、双盲、安慰剂对照试验

 背景

感染艾滋病毒的妇女早产的风险增加。一些试验表明，17α-羟基孕酮己酸酯 (17P) 可以减少有自发性早产史的妇女的早产。我们调查了 17P 是否会降低感染艾滋病毒的女性的这种风险。

 方法

我们在赞比亚卢萨卡的大学教学医院和卡姆瓦拉地区卫生中心对感染艾滋病毒的孕妇进行了一项随机、双盲、安慰剂对照试验。符合条件的患者是年满 18 岁或以上、确诊 HIV-1 感染、妊娠 24 周以内的宫内单胎妊娠、并且在怀孕期间正在接受或打算开始抗逆转录病毒治疗的女性。排除标准是严重的子宫或胎儿异常；计划或原位宫颈环扎术；筛查时有先兆流产、早产或胎膜破裂的证据； 17P 的医疗禁忌症；以前参加过试验；或自发性早产史。符合条件的参与者提供了书面知情同意书，并被随机分配（1:1），每周接受一次 250 mg 肌注 17P 或安慰剂，从妊娠 16 至 24 周开始，直至分娩、死产或足月（37 周）。参与者和研究人员对分配情况不知情，但药房工作人员除外，他们进行随机分配并准备注射，但不与参与者互动。主要结局是 37 周前分娩或任何胎龄死产的综合结果。患者每周接受研究药物注射和产前护理的访视。我们根据治疗意向估计了治疗组之间主要结局和安全事件风险的绝对和相对差异。该试验已在 ClinicalTrials.gov 注册（NCT03297216）并已完成。

 发现

2018 年 2 月 7 日至 2020 年 1 月 13 日期间，我们评估了 1042 名女性纳入这项研究。经过额外评估后，242 名女性被排除，800 名符合条件的患者被纳入并随机分配接受肌内 17P (n=399) 或安慰剂 (n=401)。各组之间的基线特征相似。两组对研究药物注射的依从率为 98%，没有患者失访，最后一次产后访视于 2020 年 8 月 6 日。分配到 17P 的 399 名参与者中有 36 名 (9%) 患有早产或早产死产，而 401 名接受安慰剂的患者中有 36 名 (9%) 出现死产（风险差异 0·1，95% CI -3·9 至 4·0；相对风险 1·0，95% CI 0·6 至 1·6） ；p=0·98)。 800 名参与者中有 140 名 (18%) 报告了与干预相关的不良事件，并且在两个随机分组中发生的比例相似。没有报告严重不良事件。

 解释

尽管 17P 似乎是安全的并且可以被参与者接受，但现有数据并不支持使用该药物来预防仅因 HIV 感染而导致早产的妇女。两个随机分组的早产风险均较低，值得进一步研究。

 资金

美国国立卫生研究院和比尔及梅琳达·盖茨基金会。