Department of Obstetrics and Gynecology, Hôpital Louis Mourier, Colombes Department of Epidemiology, Centre de Recherche en Épidémiologie et Santé des Populations, Institut National de la Santé et de la Recherche Médicale (INSERM) U1018, Le Kremlin-Bicêtre.
Department of Epidemiology, Centre de Recherche en Épidémiologie et Santé des Populations, Institut National de la Santé et de la Recherche Médicale (INSERM) U1018, Le Kremlin-Bicêtre.
Clin Infect Dis. 2015 Jul 15;61(2):270-80. doi: 10.1093/cid/civ260. Epub 2015 Apr 1.
Antiretroviral (ARV) regimens during pregnancy are highly effective in preventing mother-to-child transmission of human immunodeficiency virus (HIV). Congenital heart defects (CHDs) and anomalies in cardiac function have been reported in zidovudine (ZDV)-exposed uninfected children. We explored these associations in a large observational cohort and a randomized clinical trial.
Since 1986, the French Perinatal Cohort prospectively enrolled all HIV-infected women in 90 centers and collected follow-up on their children through 2 years of age. All CHDs were reviewed by a specialist blinded to exposures. Additionally, in a randomized trial (PRIMEVA ANRS 135) of 2 ARV regimens during pregnancy, 1 of which was without nucleoside reverse transcriptase inhibitors, infants had a specific follow-up including echocardiography at 1 month and 12 months.
Among 12 888 children included, ZDV exposure in the first trimester was significantly associated with CHD (1.5% vs 0.7%; adjusted odds ratio, 2.2 [95% confidence interval, 1.3-3.7]; P < .001). This association was significant for ventricular septal defects (1.1% vs 0.6%; P = .001) and other CHDs (0.31% vs 0.11%; P = .02). In the randomized trial, among 50 infants, girls (but not boys) exposed in utero to ZDV/lamivudine/ritonavir-boosted lopinavir (LPV/r) had a higher left ventricular shortening fraction at 1 month (40% vs 36%; P = .008), and an increased posterior wall thickness at 1 year (5.4 mm vs 4.4 mm; P = .01) than the LPV/r group.
This study confirms a specific association between in utero exposure to ZDV and CHDs, and a long-lasting postnatal myocardial remodeling in girls. A potential common mechanism, including the involvement of mitochondrial dysfunction, must be explored, and long-term consequences on cardiac function warrant specific attention.
NCT00424814.
抗逆转录病毒（ARV）方案在妊娠期间可有效预防人类免疫缺陷病毒（HIV）母婴传播。已有报道称，在齐多夫定（ZDV）暴露的未感染儿童中存在先天性心脏缺陷（CHD）和心脏功能异常。我们在一个大型观察性队列和一项随机临床试验中探讨了这些关联。
自 1986 年以来，法国围产期队列前瞻性地招募了 90 个中心的所有 HIV 感染孕妇，并通过 2 岁时对其子女进行随访。所有 CHD 均由一名对暴露情况不知情的专家进行审查。此外，在一项怀孕期间使用 2 种 ARV 方案的随机试验（PRIMEVA ANRS 135）中，其中 1 种方案不含核苷逆转录酶抑制剂，婴儿在 1 个月和 12 个月时进行特定的超声心动图随访。
在纳入的 12888 名儿童中，ZDV 在孕早期的暴露与 CHD 显著相关（1.5%比 0.7%；调整后的优势比，2.2[95%置信区间，1.3-3.7]；P<0.001）。这种关联在室间隔缺损（1.1%比 0.6%；P=0.001）和其他 CHD（0.31%比 0.11%；P=0.02）中也很显著。在随机试验中，在 50 名婴儿中，暴露于 ZDV/拉米夫定/利托那韦增强洛匹那韦（LPV/r）的女婴（而非男婴）在 1 个月时左心室短轴缩短率较高（40%比 36%；P=0.008），在 1 岁时后室间隔厚度增加（5.4 毫米比 4.4 毫米；P=0.01）。
这项研究证实了在子宫内暴露于 ZDV 与 CHD 之间存在特定的关联，以及在女孩中存在持久的产后心肌重塑。必须探索一种潜在的共同机制，包括线粒体功能障碍的参与，并且有必要特别关注对心脏功能的长期影响。
NCT00424814。
