Connor E M, Sperling R S, Gelber R, Kiselev P, Scott G, O'Sullivan M J, VanDyke R, Bey M, Shearer W, Jacobson R L
Department of Pediatrics, University of Medicine and Dentistry of New Jersey, New Jersey Medical School, Newark.
N Engl J Med. 1994 Nov 3;331(18):1173-80. doi: 10.1056/NEJM199411033311801.
Maternal-infant transmission is the primary means by which young children become infected with human immunodeficiency virus type 1 (HIV). We conducted a randomized, double-blind, placebo-controlled trial of the efficacy and safety of zidovudine in reducing the risk of maternal-infant HIV transmission. HIV-infected pregnant women (14 to 34 weeks' gestation) with CD4+ T-lymphocyte counts above 200 cells per cubic millimeter who had not received antiretroviral therapy during the current pregnancy were enrolled. The zidovudine regimen included antepartum zidovudine (100 mg orally five times daily), intrapartum zidovudine (2 mg per kilogram of body weight given intravenously over one hour, then 1 mg per kilogram per hour until delivery), and zidovudine for the newborn (2 mg per kilogram orally every six hours for six weeks). Infants with at least one positive HIV culture of peripheral-blood mononuclear cells were classified as HIV-infected.
From April 1991 through December 20, 1993, the cutoff date for the first interim analysis of efficacy, 477 pregnant women were enrolled; during the study period, 409 gave birth to 415 live-born infants. HIV-infection status was known for 363 births (180 in the zidovudine group and 183 in the placebo group). Thirteen infants in the zidovudine group and 40 in the placebo group were HIV-infected. The proportions infected at 18 months, as estimated by the Kaplan-Meier method, were 8.3 percent (95 percent confidence interval, 3.9 to 12.8 percent) in the zidovudine group and 25.5 percent (95 percent confidence interval, 18.4 to 32.5 percent) in the placebo group. This corresponds to a 67.5 percent (95 percent confidence interval, 40.7 to 82.1 percent) relative reduction in the risk of HIV transmission (Z = 4.03, P = 0.00006). Minimal short-term toxic effects were observed. The level of hemoglobin at birth in the infants in the zidovudine group was significantly lower than that in the infants in the placebo group. By 12 weeks of age, hemoglobin values in the two groups were similar.
In pregnant women with mildly symptomatic HIV disease and no prior treatment with antiretroviral drugs during the pregnancy, a regimen consisting of zidovudine given ante partum and intra partum to the mother and to the newborn for six weeks reduced the risk of maternal-infant HIV transmission by approximately two thirds.
母婴传播是幼儿感染1型人类免疫缺陷病毒（HIV）的主要途径。我们进行了一项随机、双盲、安慰剂对照试验，以评估齐多夫定降低母婴HIV传播风险的疗效和安全性。入选的是孕期14至34周、CD4+T淋巴细胞计数高于每立方毫米200个细胞且在本次妊娠期间未接受抗逆转录病毒治疗的HIV感染孕妇。齐多夫定治疗方案包括产前齐多夫定（口服100毫克，每日5次）、产时齐多夫定（每公斤体重2毫克静脉滴注1小时，然后每公斤体重每小时1毫克直至分娩）以及给新生儿使用的齐多夫定（每公斤体重2毫克，每6小时口服1次，共6周）。外周血单个核细胞HIV培养至少一次呈阳性的婴儿被归类为HIV感染。
从1991年4月至1993年12月20日（疗效首次中期分析的截止日期），共纳入477名孕妇；在研究期间，409名孕妇分娩了415名活产婴儿。已知363例分娩的HIV感染状况（齐多夫定组180例，安慰剂组183例）。齐多夫定组有13名婴儿感染HIV，安慰剂组有40名婴儿感染HIV。采用Kaplan-Meier方法估计，齐多夫定组18个月时的感染比例为8.3%（95%置信区间为3.9%至12.8%），安慰剂组为25.5%（95%置信区间为18.4%至32.5%）。这相当于HIV传播风险相对降低了67.5%（95%置信区间为40.7%至82.1%）（Z = 4.03，P = 0.00006）。观察到的短期毒性作用极小。齐多夫定组婴儿出生时的血红蛋白水平显著低于安慰剂组婴儿。到12周龄时，两组的血红蛋白值相似。
对于孕期有轻度症状的HIV疾病且在孕期未接受过抗逆转录病毒药物治疗的孕妇，由母亲产前和产时以及新生儿服用6周齐多夫定组成的治疗方案可将母婴HIV传播风险降低约三分之二。
