在乌干达坎帕拉，与齐多夫定相比，分娩期及新生儿单剂量奈韦拉平预防HIV-1母婴传播的效果：HIVNET 012随机试验的18个月随访

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.

作者信息

Jackson J Brooks, Musoke Philippa, Fleming Thomas, Guay Laura A, Bagenda Danstan, Allen Melissa, Nakabiito Clemensia, Sherman Joseph, Bakaki Paul, Owor Maxensia, Ducar Constance, Deseyve Martina, Mwatha Anthony, Emel Lynda, Duefield Corey, Mirochnick Mark, Fowler Mary Glenn, Mofenson Lynne, Miotti Paolo, Gigliotti Maria, Bray Dorothy, Mmiro Francis

机构信息

Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.

出版信息

Lancet. 2003 Sep 13;362(9387):859-68. doi: 10.1016/S0140-6736(03)14341-3.

DOI:10.1016/S0140-6736(03)14341-3

PMID:13678973

Abstract

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 2mg/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, regimenB). 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.

摘要

背景

1999年，我们报道了乌干达一项围产期HIV-1预防试验中短程奈韦拉平的安全性和有效性数据，当时对496名婴儿随访至14 - 16周龄。现在呈现的是对所有婴儿随访至18个月龄时的安全性和有效性数据。

方法

从1997年11月至1999年4月，乌干达坎帕拉的HIV-1感染孕妇被随机分配接受奈韦拉平（分娩开始时200毫克，婴儿出生后72小时内2毫克/千克；方案A）或齐多夫定（分娩开始时口服600毫克，每3小时300毫克直至分娩，婴儿口服4毫克/千克每日两次共7天，方案B）。婴儿在出生时、6 - 8周龄、14 - 16周龄以及12个月龄时通过HIV-1 RNA聚合酶链反应进行HIV-1检测，并在18个月龄时通过HIV-1抗体检测。使用Kaplan-Meier分析评估HIV-1传播和无HIV-1存活情况。我们记录了母亲产后6 - 8周以及婴儿18个月时的不良经历。疗效分析采用意向性治疗。

结果

我们招募了645名母亲参与研究：313名被分配至方案A，313名至方案B，19名接受安慰剂治疗。8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）。齐多夫定组和奈韦拉平组出生时HIV-1传播的估计风险分别为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个月龄时分别为25.8%和15.7%（p = 0.0023）。奈韦拉平与至18个月龄时传播相对风险降低41%（95%CI 16 - 59）相关。两种方案耐受性良好，严重副作用很少。

解读

与短程的分娩期/新生儿期齐多夫定方案相比，分娩期/新生儿期奈韦拉平显著降低了乌干达母乳喂养人群中HIV-1的传播风险。6 - 8周龄时传播绝对降低8.2%在18个月龄时仍持续存在（10.1% [95%CI 3.5 - 16.6]）。这种简单、廉价且耐受性良好的方案有可能在欠发达国家显著降低HIV-1围产期传播。