Lockman Shahin, Shapiro Roger L, Smeaton Laura M, Wester Carolyn, Thior Ibou, Stevens Lisa, Chand Fatima, Makhema Joseph, Moffat Claire, Asmelash Aida, Ndase Patrick, Arimi Peter, van Widenfelt Erik, Mazhani Loeto, Novitsky Vladimir, Lagakos Stephen, Essex Max
Division of Infectious Diseases, Brigham and Women's Hospital, Boston, MA 02115, USA.
N Engl J Med. 2007 Jan 11;356(2):135-47. doi: 10.1056/NEJMoa062876.
A single dose of nevirapine during labor reduces perinatal transmission of human immunodeficiency virus type 1 (HIV-1) but often leads to viral nevirapine resistance mutations in mothers and infants.
We studied the response to nevirapine-based antiretroviral treatment among women and infants who had previously been randomly assigned to a single, peripartum dose of nevirapine or placebo in a trial in Botswana involving the prevention of the transmission of HIV-1 from mother to child. All women were treated with antenatal zidovudine. The primary end point for mothers and infants was virologic failure by the 6-month visit after initiation of antiretroviral treatment, estimated within groups by the Kaplan-Meier method.
Of 218 women who started antiretroviral treatment, 112 had received a single dose of nevirapine and 106 had received placebo. By the 6-month visit after the initiation of antiretroviral treatment, 5.0% of the women who had received placebo had virologic failure, as compared with 18.4% of those who had received a single dose of nevirapine (P=0.002). Among 60 women starting antiretroviral treatment within 6 months after receiving placebo or a single dose of nevirapine, no women in the placebo group and 41.7% in the nevirapine group had virologic failure (P<0.001). In contrast, virologic failure rates did not differ significantly between the placebo group and the nevirapine group among 158 women starting antiretroviral treatment 6 months or more post partum (7.8% and 12.0%, respectively; P=0.39). Thirty infants also began antiretroviral treatment (15 in the placebo group and 15 in the nevirapine group). Virologic failure by the 6-month visit occurred in significantly more infants who had received a single dose of nevirapine than in infants who had received placebo (P<0.001). Maternal and infant findings did not change qualitatively by 12 and 24 months after the initiation of antiretroviral treatment.
Women who received a single dose of nevirapine to prevent perinatal transmission of HIV-1 had higher rates of virologic failure with subsequent nevirapine-based antiretroviral therapy than did women without previous exposure to nevirapine. However, this applied only when nevirapine-based antiretroviral therapy was initiated within 6 months after receipt of a single, peripartum dose of nevirapine. (ClinicalTrials.gov number, NCT00197587 [ClinicalTrials.gov].).
分娩时单剂量奈韦拉平可降低人类免疫缺陷病毒1型（HIV-1）的围产期传播，但常导致母亲和婴儿出现奈韦拉平病毒耐药突变。
在博茨瓦纳一项预防HIV-1母婴传播的试验中，我们研究了曾被随机分配接受单剂量围产期奈韦拉平或安慰剂的妇女及其婴儿对基于奈韦拉平的抗逆转录病毒治疗的反应。所有妇女均接受产前齐多夫定治疗。母亲和婴儿的主要终点是开始抗逆转录病毒治疗后6个月随访时的病毒学失败，采用Kaplan-Meier方法在组内进行估计。
开始抗逆转录病毒治疗的218名妇女中，112名接受了单剂量奈韦拉平，106名接受了安慰剂。开始抗逆转录病毒治疗后6个月随访时，接受安慰剂的妇女中有5.0%出现病毒学失败，而接受单剂量奈韦拉平的妇女中有18.4%出现病毒学失败（P=0.002）。在接受安慰剂或单剂量奈韦拉平后6个月内开始抗逆转录病毒治疗的60名妇女中，安慰剂组无妇女出现病毒学失败，奈韦拉平组有41.7%的妇女出现病毒学失败（P<0.001）。相比之下，产后6个月或更长时间开始抗逆转录病毒治疗的158名妇女中，安慰剂组和奈韦拉平组的病毒学失败率无显著差异（分别为7.8%和12.0%；P=0.39）。30名婴儿也开始了抗逆转录病毒治疗（安慰剂组15名，奈韦拉平组15名）。开始抗逆转录病毒治疗后6个月随访时，接受单剂量奈韦拉平的婴儿出现病毒学失败的比例显著高于接受安慰剂的婴儿（P<0.001）。开始抗逆转录病毒治疗后12个月和24个月时，母婴的结果在性质上没有变化。
接受单剂量奈韦拉平预防HIV-1围产期传播的妇女，与未接触过奈韦拉平的妇女相比，后续基于奈韦拉平的抗逆转录病毒治疗的病毒学失败率更高。然而，这仅适用于在接受单剂量围产期奈韦拉平后6个月内开始基于奈韦拉平的抗逆转录病毒治疗的情况。（ClinicalTrials.gov编号，NCT00197587 [ClinicalTrials.gov]。）
