Institute of Tropical Medicine and International Health, Charité - Universitätsmedizin Berlin, Berlin, Germany.
PLoS One. 2012;7(2):e32055. doi: 10.1371/journal.pone.0032055. Epub 2012 Feb 23.
WHO-guidelines for prevention of mother-to-child transmission of HIV-1 in resource-limited settings recommend complex maternal antiretroviral prophylaxis comprising antenatal zidovudine (AZT), nevirapine single-dose (NVP-SD) at labor onset and AZT/lamivudine (3TC) during labor and one week postpartum. Data on resistance development selected by this regimen is not available. We therefore analyzed the emergence of minor drug-resistant HIV-1 variants in Tanzanian women following complex prophylaxis.
1395 pregnant women were tested for HIV-1 at Kyela District Hospital, Tanzania. 87/202 HIV-positive women started complex prophylaxis. Blood samples were collected before start of prophylaxis, at birth and 1-2, 4-6 and 12-16 weeks postpartum. Allele-specific real-time PCR assays specific for HIV-1 subtypes A, C and D were developed and applied on samples of mothers and their vertically infected infants to quantify key resistance mutations of AZT (K70R/T215Y/T215F), NVP (K103N/Y181C) and 3TC (M184V) at detection limits of <1%.
50/87 HIV-infected women having started complex prophylaxis were eligible for the study. All women took AZT with a median duration of 53 days (IQR 39-64); all women ingested NVP-SD, 86% took 3TC. HIV-1 resistance mutations were detected in 20/50 (40%) women, of which 70% displayed minority species. Variants with AZT-resistance mutations were found in 11/50 (22%), NVP-resistant variants in 9/50 (18%) and 3TC-resistant variants in 4/50 women (8%). Three women harbored resistant HIV-1 against more than one drug. 49/50 infants, including the seven vertically HIV-infected were breastfed, 3/7 infants exhibited drug-resistant virus.
Complex prophylaxis resulted in lower levels of NVP-selected resistance as compared to NVP-SD, but AZT-resistant HIV-1 emerged in a substantial proportion of women. Starting AZT in pregnancy week 14 instead of 28 as recommended by the current WHO-guidelines may further increase the frequency of AZT-resistance mutations. Given its impact on HIV-transmission rate and drug-resistance development, HAART for all HIV-positive pregnant women should be considered.
世界卫生组织（WHO）发布的资源有限地区预防 HIV-1 母婴传播指南推荐采用包含产前齐多夫定（AZT）、分娩时单剂量奈韦拉平（NVP-SD）以及分娩时和产后一周内 AZT/拉米夫定（3TC）的复杂抗逆转录病毒预防方案。该方案并未选择针对耐药性的药物，因此我们分析了坦桑尼亚妇女在采用该复杂方案预防后的 HIV-1 耐药情况。
1395 名孕妇在坦桑尼亚 Kyela 区医院接受了 HIV-1 检测。202 名 HIV 阳性孕妇中有 87 名开始采用复杂预防方案。在开始预防前、分娩时以及产后 1-2、4-6 和 12-16 周采集血样。我们开发并应用了针对 HIV-1 亚型 A、C 和 D 的等位基因特异性实时 PCR 检测方法，对母亲及其垂直感染婴儿的样本进行检测，以定量检测 AZT（K70R/T215Y/T215F）、NVP（K103N/Y181C）和 3TC（M184V）的关键耐药突变，检测限为<1%。
87 名开始采用复杂预防方案的 HIV 感染者中有 50 名符合研究条件。所有妇女均服用 AZT，中位疗程为 53 天（IQR 39-64）；所有妇女均服用 NVP-SD，86%服用 3TC。50 名妇女中有 20 名（40%）检测到 HIV-1 耐药突变，其中 70%为少数种群。50 名妇女中有 11 名（22%）发现 AZT 耐药突变，9 名（18%）发现 NVP 耐药突变，4 名（8%）发现 3TC 耐药突变。3 名妇女对一种以上药物具有耐药性。50 名婴儿中包括 7 名垂直感染的婴儿，其中 49 名进行了母乳喂养，3 名婴儿携带耐药病毒。
与 NVP-SD 相比，复杂预防方案导致 NVP 选择的耐药水平较低，但仍有相当一部分妇女出现了 AZT 耐药性。根据目前的 WHO 指南，建议在妊娠第 14 周而非第 28 周开始服用 AZT，这可能会进一步增加 AZT 耐药突变的频率。鉴于其对 HIV 传播率和耐药性发展的影响，所有 HIV 阳性孕妇均应考虑采用高效抗逆转录病毒治疗（HAART）。
