University of Alabama at Birmingham Centre for Infectious Disease Research in Zambia, Lusaka, Zambia.
PLoS Med. 2010 Feb 16;7(2):e1000233. doi: 10.1371/journal.pmed.1000233.
Intrapartum and neonatal single-dose nevirapine (NVP) reduces the risk of mother-to-child HIV transmission but also induces viral resistance to non-nucleoside reverse transcriptase inhibitor (NNRTI) drugs. This drug resistance largely fades over time. We hypothesized that women with a prior single-dose NVP exposure would have no more than a 10% higher cumulative prevalence of failure of their NNRTI-containing antiretroviral therapy (ART) over the first 48 wk of therapy than would women without a prior exposure.
We enrolled 355 NVP-exposed and 523 NVP-unexposed women at two sites in Zambia, one site in Kenya, and two sites in Thailand into a prospective, non-inferiority cohort study and followed them for 48 wk on ART. Those who died, discontinued NNRTI-containing ART, or had a plasma viral load >or=400 copies/ml at either the 24 wk or 48 wk study visits and confirmed on repeat testing were characterized as having failed therapy. Overall, 114 of 355 NVP-exposed women (32.1%) and 132 of 523 NVP-unexposed women (25.2%) met criteria for treatment failure. The difference in failure rates between the exposure groups was 6.9% (95% confidence interval [CI] 0.8%-13.0%). The failure rates of women stratified by our predefined exposure interval categories were as follows: 47 of 116 women in whom less than 6 mo elapsed between exposure and starting ART failed therapy (40%; p<0.001 compared to unexposed women); 25 of 67 women in whom 7-12 mo elapsed between exposure and starting ART failed therapy (37%; p = 0.04 compared to unexposed women); and 42 of 172 women in whom more than 12 mo elapsed between exposure and starting ART failed therapy (24%; p = 0.82 compared to unexposed women). Locally weighted regression analysis also indicated a clear inverse relationship between virologic failure and the exposure interval.
Prior exposure to single-dose NVP was associated with an increased risk of treatment failure; however, this risk seems largely confined to women with a more recent exposure. Women requiring ART within 12 mo of NVP exposure should not be prescribed an NNRTI-containing regimen as first-line therapy.
产时和新生儿单剂量奈韦拉平（NVP）可降低母婴 HIV 传播的风险，但也会导致对非核苷类逆转录酶抑制剂（NNRTI）药物的病毒耐药性。这种耐药性随着时间的推移而大大消失。我们假设，与没有单次 NVP 暴露史的女性相比，单次 NVP 暴露的女性在接受含 NNRTI 的抗逆转录病毒治疗（ART）的最初 48 周内，其 NNRTI 治疗失败的累积患病率不会超过 10%。
我们在赞比亚的两个地点、肯尼亚的一个地点和泰国的两个地点招募了 355 名 NVP 暴露女性和 523 名 NVP 未暴露女性，进行了一项前瞻性、非劣效性队列研究，并在接受 ART 治疗的 48 周内对她们进行了随访。那些死亡、停止使用含 NNRTI 的 ART 或在 24 周或 48 周研究访视时血浆病毒载量≥400 拷贝/ml 且在重复检测中得到证实的患者被认为治疗失败。总的来说，355 名 NVP 暴露女性中有 114 名（32.1%）和 523 名 NVP 未暴露女性中有 132 名（25.2%）符合治疗失败标准。暴露组之间的失败率差异为 6.9%（95%置信区间[CI]0.8%-13.0%）。按我们预定义的暴露间隔类别分层的女性失败率如下：在暴露和开始 ART 之间不到 6 个月的 116 名女性中有 47 名（40%；与未暴露女性相比，p<0.001）；在暴露和开始 ART 之间 7-12 个月的 67 名女性中有 25 名（37%；与未暴露女性相比，p=0.04）；在暴露和开始 ART 之间超过 12 个月的 172 名女性中有 42 名（24%；与未暴露女性相比，p=0.82）。局部加权回归分析也表明，病毒学失败与暴露间隔之间存在明显的反比关系。
单次 NVP 暴露与治疗失败风险增加相关；然而，这种风险似乎主要局限于最近暴露的女性。在 NVP 暴露后 12 个月内需要接受 ART 的女性不应将含 NNRTI 的方案作为一线治疗。
