Intrapartum and neonatal single-dose nevirapine compared with zidovudine for prevention of mother-to-child transmission of HIV-1 in Kampala, Uganda: 18-month follow-up of the HIVNET 012 randomised trial
Intrapartum and neonatal single-dose nevirapine compared with zidovudine for prevention of mother-to-child transmission of HIV-1 in Kampala, Uganda: 18-month follow-up of the HIVNET 012 randomised trial
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DOI：
10.1016/s0140-6736(03)14341-3
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发表时间：
2003-09-13
期刊：
影响因子：
168.9
通讯作者：
Mmiro, F
中科院分区：
文献类型：
--
作者：
Jackson, JB;Musoke, P;Mmiro, F
背景 1999 年，我们报告了乌干达围产期 HIV-1 预防试验中短期奈韦拉平的安全性和有效性数据，该试验对 496 名婴儿进行了随访，直至 14-16 周。现提供所有 18 个月大婴儿的安全性和有效性数据。 方法 从 1997 年 11 月到 1999 年 4 月，乌干达坎帕拉感染 HIV-1 的孕妇被随机分配奈韦拉平（临产时 200 mg，出生后 72 小时内婴儿 2 mg/kg；方案 A）或齐多夫定（临产时口服 600 mg，每次 300 mg）。 3 小时直至分娩，婴儿每日两次口服 4 mg/kg，持续 7 天，方案 B)。婴儿 HIV-1 检测是在出生时、6-8 岁、14-16 周和 12 个月时通过 HIV-1 RNA PCR 进行的，并在 18 个月时通过 HIV-1 抗体进行的。使用 Kaplan-Meier 分析评估 HIV-1 传播和无 HIV-1 生存率。我们记录了母亲产后 6-8 周和婴儿产后 18 个月的不良经历。功效分析是按意向治疗进行的。结果 我们招募了 645 名母亲参加研究：313 名母亲接受方案 A，313 名母亲接受方案 B，19 名母亲接受安慰剂。八名母亲在分娩前失访。 99% 的婴儿接受母乳喂养（中位持续时间 9 个月）。齐多夫定和奈韦拉平组的出生时 HIV-1 传播估计风险分别为 10.3% 和 8.1%（p=0.35）； 6-8 周龄时分别为 20.0% 和 11.8% (p=0.0063)； 14-16 周龄时分别为 22.1% 和 13.5% (p=0.0064)； 18 个月时分别为 25.8% 和 15.7% (p=0.0023)。奈韦拉平可将 18 个月以下的相对传播风险降低 41% (95% CI 16-59)。两种治疗方案均具有良好的耐受性，几乎没有严重的副作用。 解释 与短期产时/新生儿齐多夫定治疗方案相比，产时/新生儿奈韦拉平显着降低了乌干达母乳喂养人群中 HIV-1 的传播风险。 6-8 周时传播绝对减少 8.2%，并持续到 18 个月大时（10.1% [95% CI 3.5-16.6]）。这种简单、廉价、耐受性良好的治疗方案有可能显着减少欠发达国家的 HIV-1 围产期传播。
Background In 1999, we reported safety and efficacy data for short-course nevirapine from a Ugandan perinatal HIV-1 prevention trial when 496 babies were followed up to age 14-16 weeks. Safety and efficacy data are now presented for all babies followed up to 18 months of age.Methods From November, 1997, to April, 1999, HIV-1 infected pregnant women in Kampala, Uganda, were randomly assigned nevirapine (200 mg at labour onset and 2 mg/kg for babies within 72 h of birth; regimen A) or zidovudine (600 mg orally at labour onset and 300 mg every 3 h until delivery, and 4 mg/kg orally twice daily for babies for 7 days, regimen B). Infant HIV-1 testing was done at birth, age 6-8 and 14-16 weeks, and age 12 months by HIV-1 RNA PCR, and by HIV-1 antibody at 18 months. HIV-1 transmission and HIV-1-free survival were assessed using Kaplan-Meier analysis. We recorded adverse experiences through 6-8 weeks postpartum for mothers, and 18 months for babies. Efficacy analyses were by intention to treat.Findings We enrolled 645 mothers to the study: 313 were assigned regimen A, 313 regimen B, and 19 placebo. Eight mothers were lost to follow-up before delivery. 99% of babies were breastfed (median duration 9 months). Estimated risks of HIV-1 transmission in the zidovudine and nevirapine groups were 10.3% and 8.1% at birth (p=0.35); 20.0% and 11.8% by age 6-8 weeks (p=0.0063); 22.1% and 13.5% by age 14-16 weeks (p=0.0064); and 25.8% and 15.7% by age 18 months (p=0.0023). Nevirapine was associated with a 41% (95% CI 16-59) reduction in relative risk of transmission through to age 18 months. Both regimens were well-tolerated with few serious side-effects.Interpretation Intrapartum/neonatal nevirapine significantly lowered HIV-1 transmission risk in a breastfeeding population in Uganda compared with a short intrapartum/neonatal zidovudine regimen. The absolute 8.2% reduction in transmission at 6-8 weeks was sustained at age 18 months (10.1% [95% CI 3.5-16.6]). This simple, inexpensive, well-tolerated regimen has the potential to significantly decrease HIV-1 perinatal transmission in less-developed countries.