Maternal Adolescent and Child Health (MatCH), University of the Witwatersrand, Johannesburg, South Africa.
Lancet. 2012 Jan 21;379(9812):221-8. doi: 10.1016/S0140-6736(11)61653-X. Epub 2011 Dec 22.
Nevirapine given once-daily for the first 6, 14, or 28 weeks of life to infants exposed to HIV-1 via breastfeeding reduces transmission through this route compared with single-dose nevirapine at birth or neonatally. We aimed to assess incremental safety and efficacy of extension of such prophylaxis to 6 months.
In our phase 3, randomised, double-blind, placebo-controlled HPTN 046 trial, we assessed the incremental benefit of extension of once-daily infant nevirapine from age 6 weeks to 6 months. We enrolled breastfeeding infants born to mothers with HIV-1 in four African countries within 7 days of birth. Following receipt of nevirapine from birth to 6 weeks, infants without HIV infection were randomly allocated (by use of a computer-generated permuted block algorithm with random block sizes and stratified by site and maternal antiretroviral treatment status) to receive extended nevirapine prophylaxis or placebo until 6 months or until breastfeeding cessation, whichever came first. The primary efficacy endpoint was HIV-1 infection in infants at 6 months and safety endpoints were adverse reactions in both groups. We used Kaplan-Meier analyses to compare differences in the primary outcome between groups. This study is registered with ClinicalTrials.gov, number NCT00074412.
Between June 19, 2008, and March 12, 2010, we randomly allocated 1527 infants (762 nevirapine and 765 placebo); five of whom had HIV-1 infection at randomisation and were excluded from the primary analyses. In Kaplan-Meier analysis, 1·1% (95% CI 0·3-1·8) of infants who received extended nevirapine developed HIV-1 between 6 weeks and 6 months compared with 2·4% (1·3-3·6) of controls (difference 1·3%, 95% CI 0-2·6), equating to a 54% reduction in transmission (p=0·049). However, mortality (1·2% for nevirapine vs 1·1% for placebo; p=0·81) and combined HIV infection and mortality rates (2·3%vs 3·2%; p=0·27) did not differ between groups at 6 months. 125 (16%) of 758 infants given extended nevirapine and 116 (15%) of 761 controls had serious adverse events, but frequency of adverse events, serious adverse events, and deaths did not differ significantly between treatment groups.
Nevirapine prophylaxis can safely be used to provide protection from mother-to-child transmission of HIV-1 via breastfeeding for infants up to 6 months of age.
US National Institutes of Health.
在感染 HIV-1 的婴儿通过母乳喂养暴露的情况下，与单剂量出生时或新生儿时给予奈韦拉平相比，奈韦拉平每天一次给药用于生命的前 6、14 或 28 周，可降低通过该途径的传播。我们旨在评估将这种预防措施延长至 6 个月的额外安全性和疗效。
在我们的 3 期、随机、双盲、安慰剂对照 HPTN 046 试验中，我们评估了延长婴儿每天一次奈韦拉平从 6 周龄到 6 个月龄的额外益处。我们在出生后 7 天内在四个非洲国家招募了 HIV-1 阳性母亲所生的母乳喂养婴儿。在接受出生至 6 周龄的奈韦拉平治疗后，未感染 HIV 的婴儿按（使用基于计算机生成的随机化块算法，具有随机块大小，并按地点和产妇抗逆转录病毒治疗状况分层）随机分配接受延长奈韦拉平预防治疗或安慰剂，直至 6 个月龄或母乳喂养停止，以先到者为准。主要疗效终点是婴儿在 6 个月龄时的 HIV-1 感染，安全性终点是两组的不良反应。我们使用 Kaplan-Meier 分析比较两组之间主要结局的差异。本研究在 ClinicalTrials.gov 注册，编号为 NCT00074412。
在 2008 年 6 月 19 日至 2010 年 3 月 12 日期间，我们随机分配了 1527 名婴儿（762 名接受奈韦拉平，765 名接受安慰剂）；其中 5 名婴儿在随机分组时已感染 HIV-1，被排除在主要分析之外。在 Kaplan-Meier 分析中，接受延长奈韦拉平治疗的婴儿在 6 周龄至 6 个月龄之间有 1.1%（95%CI 0.3-1.8）发生 HIV-1，而对照组为 2.4%（1.3-3.6）（差异 1.3%，95%CI 0-2.6），相当于传播减少 54%（p=0.049）。然而，死亡率（奈韦拉平组为 1.2%，安慰剂组为 1.1%；p=0.81）和合并 HIV 感染和死亡率（奈韦拉平组为 2.3%，安慰剂组为 3.2%；p=0.27）在 6 个月时两组之间无差异。接受延长奈韦拉平治疗的 758 名婴儿中有 125 名（16%）和接受安慰剂治疗的 761 名对照组中有 116 名（15%）发生严重不良事件，但治疗组之间不良事件、严重不良事件和死亡的频率无显著差异。
奈韦拉平预防治疗可安全用于为通过母乳喂养感染 HIV-1 的婴儿提供保护，直至 6 个月龄。
美国国立卫生研究院。
