Intrapartum exposure to nevirapine and subsequent maternal responses to nevirapine-based antiretroviral therapy
Intrapartum exposure to nevirapine and subsequent maternal responses to nevirapine-based antiretroviral therapy
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DOI：
10.1056/nejmoa041305
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发表时间：
2004-07-15
影响因子：
158.5
通讯作者：
Lallemant, M
中科院分区：
文献类型：
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作者：
Jourdain, G;Ngo-Giang-Huong, N;Lallemant, M
背景：分娩期单剂量奈韦拉平预防人类免疫缺陷病毒（HIV）母婴传播导致耐药突变的选择。是否有临床上显着的后果，在母亲谁是随后治疗的nevirapine含regimeneration.METHODS：我们随机分配1844名妇女在泰国谁收到齐多夫定在妊娠晚期接受产时nevirapine或安慰剂。在产后期间，269名CD 4计数低于250个细胞/立方毫米的妇女开始接受含奈韦拉平的抗逆转录病毒治疗。在产后10天获得血浆样品并分析抗性突变。血浆HIV-1型（HIV-1）RNA测定开始前的治疗和3个月和6个月after.Results：治疗6个月后，HIV-1 RNA水平低于50拷贝每毫升的49%的妇女谁收到了分娩期奈韦拉平，相比68%的妇女谁没有收到分娩期奈韦拉平（P=0.03）。在32%分娩时接受奈韦拉平的妇女产后10天的血液样本中可检测到对非核苷类逆转录酶抑制剂的耐药突变;最常见的突变是K103 N、G190 A和Y181 C。在分娩时接受奈韦拉平治疗的妇女中，38%的耐药突变妇女和52%的无耐药突变妇女在6个月时实现了病毒抑制（P=0.08）。治疗前HIV-1 RNA水平等于或高于中位数4.53 log（sub 10）拷贝/ml和分娩时暴露于奈韦拉平与病毒学失败独立相关。治疗6个月后，两组之间的CD 4计数无显著性差异（P=0.65）。结论：产后接受奈韦拉平治疗的妇女在产后6个月内使用含奈韦拉平的治疗方案进行病毒学抑制的可能性较小。我们的数据表明，有必要制定战略，最大限度地发挥抗逆转录病毒预防母婴传播艾滋病毒和母亲抗逆转录病毒治疗的效益。
BACKGROUND:A single intrapartum dose of nevirapine for the prevention of mother-to-child transmission of human immunodeficiency virus (HIV) leads to the selection of resistance mutations. Whether there are clinically significant consequences in mothers who are subsequently treated with a nevirapine-containing regimen is unknown.METHODS:We randomly assigned 1844 women in Thailand who received zidovudine during the third trimester of pregnancy to receive intrapartum nevirapine or placebo. In the postpartum period, 269 of the women with a CD4 count below 250 cells per cubic millimeter began a nevirapine-containing antiretroviral regimen. Plasma samples were obtained 10 days post partum and analyzed for resistance mutations. Plasma HIV type 1 (HIV-1) RNA was measured before the initiation of therapy and three and six months thereafter.RESULTS:After six months of therapy, the HIV-1 RNA level was less than 50 copies per milliliter in 49 percent of the women who had received intrapartum nevirapine, as compared with 68 percent of the women who had not received intrapartum nevirapine (P=0.03). Resistance mutations to nonnucleoside reverse-transcriptase inhibitors were detectable in blood samples obtained 10 days post partum from 32 percent of the women who had received intrapartum nevirapine; the most frequent mutations were K103N, G190A, and Y181C. Among the women who had received intrapartum nevirapine, viral suppression was achieved at six months in 38 percent of those with resistance mutations and 52 percent of those without resistance mutations (P=0.08). An HIV-1 RNA level at or above the median of 4.53 log(sub 10) copies per milliliter before therapy and intrapartum exposure to nevirapine were independently associated with virologic failure. After six months of therapy, there was no significant difference between groups in the CD4 count (P=0.65).CONCLUSIONS:Women who received intrapartum nevirapine were less likely to have virologic suppression after six months of postpartum treatment with a nevirapine-containing regimen. Our data suggest the need for strategies to maximize the benefits of both antiretroviral prophylaxis against mother-to-child transmission of HIV and antiretroviral therapy for mothers.