Pregnancy Incidence and Outcomes Among Women Receiving Preexposure Prophylaxis for HIV Prevention A Randomized Clinical Trial
Pregnancy Incidence and Outcomes Among Women Receiving Preexposure Prophylaxis for HIV Prevention A Randomized Clinical Trial
复制标题
DOI：
10.1001/jama.2014.8735
复制
发表时间：
2014-07-23
影响因子：
120.7
通讯作者：
Baeten, Jared M.
中科院分区：
文献类型：
--
作者：
Mugo, Nelly R.;Hong, Ting;Baeten, Jared M.
使用富马酸替诺福韦酯（TDF）和恩曲他滨/富马酸替诺福韦酯（FTC+TDF）联合治疗的抗逆转录病毒暴露前预防（PrEP）可有效预防人类免疫缺陷病毒（HIV）感染。PrEP可降低围产期HIV感染风险，但对妊娠结局的影响尚不明确。目的评估围产期使用PrEP的妇女的妊娠发生率和结局。设计、环境和对象在1785对HIV血清不一致的异性恋夫妇中进行的随机试验（伴侣PrEP研究），其中女性伴侣未感染艾滋病毒，证明PrEP对预防艾滋病毒有效，干预每日口服TDF（n = 598），组合FTC+TDF = 566），或安慰剂（n = 621），直到2011年7月，当PrEP证明对HIV预防有效。此后，参与者继续接受积极的PrEP而不接受安慰剂。每月进行一次妊娠试验，当检测到妊娠时停止研究药物治疗。主要结局和指标妊娠发生率，出生结局（活产，妊娠丢失，早产，先天性畸形）和婴儿生长。在接受安慰剂治疗的女性中，妊娠发生率为10.0/100人-年，在接受TDF治疗的女性中为11.9/100人-年（发生率差异为1.9; 95% CI为-1.1至4.9 [P = 0.22 vs安慰剂]），在接受FTC+TDF治疗的女性中为8.8/100人-年（发生率差异为-1.3; 95% CI为-4.1至1.5 [P = 0.39 vs安慰剂]）。2011年7月安慰剂治疗组停药前，（288例妊娠中的96例），接受FTC+TDF的女性为42.5%，而接受安慰剂的女性为32.3%（FTC+TDF组与安慰剂组的差异为10.2%; 95% CI为-5.3%至25.7%; P = 0.16），而单独接受TDF组的差异为27.7%（与安慰剂相比的差异，-4.6%; 95% CI，-18.1%至8.9%; P = 0.46）。2011年7月后，FTC+TDF组的妊娠丢失率（52/143例妊娠）为37.5%，TDF单药组为36.7%（差异为0.8%; 95% CI，-16.8%至18.5%; P = 0.92）。发生早产，先天性畸形，并在整个生命的第一年的增长并没有显着差异的婴儿出生的妇女谁收到PrEP vs安慰剂。CONCLUSIONS AND RELEVANCE在HIV血清不一致的异性恋非洲夫妇，妊娠发生率，出生结果和婴儿生长的差异没有统计学差异的妇女接受PrEP与TDF单独或组合的FTC+TDF与安慰剂相比，在概念。鉴于PrEP在检测到怀孕时停止，并且出生结果的Cls很广，因此无法对PrEP在围产期的安全性做出明确的声明。这些结果应该与正在考虑怀孕的未感染艾滋病毒的妇女进行讨论。
IMPORTANCE Antiretroviral preexposure prophylaxis (PrEP), using tenofovir disoproxil fumarate (TDF) and combination emtricitabine/tenofovir disoproxil fumarate (FTC+TDF), is efficacious for prevention of human immunodeficiency virus (HIV) acquisition. PrEP could reduce periconception HIV risk, but the effect on pregnancy outcomes is not well defined.OBJECTIVE To assess pregnancy incidence and outcomes among women using PrEP during the periconception period.DESIGN, SETTING, AND PARTICIPAPITS Randomized trial among 1785 HIV-serodiscordant heterosexual couples (the Partners PrEP Study) in which the female partner was HIV uninfected that demonstrated that PrEP was efficacious for HIV prevention, conducted between July 2008 and June 2013 at 9 sites in Kenya and Uganda.INTERVENTIONS Daily oral TDF (n = 598), combination FTC+TDF = 566), or Placebo (n = 621) through July 2011, when PrEP demonstrated efficacy for HIV prevention. Thereafter, participants continued receiving active PrEP without placebo. Pregnancy testing occurred monthly and study medication was discontinued when pregnancy was detected.MAIN OUTCOMES AND MEASURES Pregnancy incidence, birth outcomes (live births, pregnancy loss, preterm birth, congenital anomalies), and infant growth.RESULTS A total of 431 pregnancies occurred. Pregnancy incidence was 10.0 Per 100 person-years among women assigned placebo, 11.9 among those assigned TDF (incidence difference, 1.9; 95% Cl, -1.1 to 4.9 [P = .22 vs placebo]), and 8.8 among those assigned FTC+TDF (incidence difference, -1.3; 95% Cl, -4.1 to 1.5 [P = .39 vs placebo]). Before discontinuation of the placebo treatment group in July 2011, the occurrence of pregnancy loss (96 of 288 pregnancies) was 42.5% for women receiving FTC+TDF compared with 32.3% for those receiving placebo (difference for FTC+TDF vs placebo, 10.2%; 95% Cl, -5.3% to 25.7%; P = .16) and was 27.7% for those receiving TDF alone (difference vs placebo, -4.6%; 95% Cl, -18.1% to 8.9%; P = .46). After July 2011, the frequency of Pregnancy loss (52 of 143 Pregnancies) was 37.5% for FTC+TDF and 36.7% for TDF alone (difference, 0.8%; 95% Cl, -16.8% to 18.5%; P = .92). Occurrence of preterm birth, congenital anomalies, and growth throughout the first year of life did not differ significantly for infants born to women who received PrEP vs placebo.CONCLUSIONS AND RELEVANCE Among HIV-serodiscordant heterosexual African couples, differences in pregnancy incidence, birth outcomes, and infant growth were not statistically different for women receiving PrEP with TDF alone or combination FTC+TDF compared with placebo at conception. Given that PrEP was discontinued when pregnancy was detected and that Cls for the birth outcomes were wide, definitive statements about the safety of PrEP in the periconception period cannot be made. These results should be discussed with HIV-uninfected women receiving PrEP who are considering becoming pregnant.