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在马拉维,基于奈韦拉平的抗逆转录病毒治疗用于预防母婴传播HIV停药18个月后的耐药性突变

Drug resistance mutations 18 months after discontinuation of nevirapine-based ART for prevention of mother-to-child transmission of HIV in Malawi.

作者信息

Palombi Leonardo, Galluzzo Clementina Maria, Andreotti Mauro, Liotta Giuseppe, Jere Haswel, Sagno Jean-Baptiste, Luhanga Richard, Mancinelli Sandro, Amici Roberta, Marazzi Maria Cristina, Vella Stefano, Giuliano Marina

机构信息

Department of Biomedicine and Prevention, University of Rome Tor Vergata, Via Montpellier 1, 00133 Rome, Italy.

Department of Therapeutic Research and Medicines Evaluation, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, Italy.

出版信息

J Antimicrob Chemother. 2015 Oct;70(10):2881-4. doi: 10.1093/jac/dkv171. Epub 2015 Jun 25.

Abstract

OBJECTIVES

The objective of this study was to determine the prevalence of drug resistance mutations among HIV-positive women in Malawi 18 months after discontinuing nevirapine-based ART for the prevention of mother-to-child transmission.

PATIENTS AND METHODS

HIV-infected antiretroviral-naive (except for single-dose nevirapine) pregnant Malawian women receiving a nevirapine-based triple antiretroviral regimen from Week 25 of gestation until 6 months of breastfeeding were included in this analysis. Drug resistance was assessed in HIV-DNA 24 months post-partum and at baseline (before the initiation of treatment). In patients with resistance, the presence of mutations was also evaluated in the corresponding plasma samples.

RESULTS

Seven out of 42 (16.7%) women studied had archived drug resistance at Month 24 [six cases had NNRTI-associated mutations and two cases the M184I mutation]. In four cases, resistance mutations were already present at baseline (all NNRTI mutations). In three cases, there was an emergence of 'new' resistance (also present in the plasma in one case). Of the 35 women without resistance mutations at Month 24, only one subject had resistance mutations at baseline. Baseline resistance was significantly more common among women with mutations at 24 months compared with those harbouring a WT virus (4/7 versus 1/35, P < 0.001).

CONCLUSIONS

Among women who had discontinued drugs 6 months post-partum, only 3/42 (7.1%) had accumulated new resistance mutations in HIV-DNA 2 years after delivery. These findings are reassuring in terms of the safety of the Option B strategy for the prevention of HIV mother-to-child transmission.

摘要

目的

本研究的目的是确定马拉维的艾滋病毒阳性女性在停用基于奈韦拉平的抗逆转录病毒治疗以预防母婴传播18个月后的耐药突变流行率。

患者和方法

纳入从妊娠第25周开始直至母乳喂养6个月接受基于奈韦拉平的三联抗逆转录病毒治疗方案的未接受过抗逆转录病毒治疗(单剂量奈韦拉平除外)的感染艾滋病毒的马拉维孕妇进行分析。在产后24个月和基线(治疗开始前)对HIV-DNA进行耐药性评估。对于有耐药性的患者,还在相应的血浆样本中评估突变的存在情况。

结果

在研究的42名女性中,有7名(16.7%)在第24个月有存档的耐药性[6例有与非核苷类逆转录酶抑制剂(NNRTI)相关的突变,2例有M184I突变]。在4例中,基线时就已存在耐药突变(均为NNRTI突变)。在3例中,出现了“新的”耐药性(1例血浆中也存在)。在第24个月没有耐药突变的35名女性中,只有1名受试者在基线时有耐药突变。与携带野生型病毒的女性相比,24个月时有突变的女性基线耐药性明显更常见(4/7对1/35,P<0.001)。

结论

在产后6个月停药的女性中,只有3/42(7.1%)在分娩后2年的HIV-DNA中积累了新的耐药突变。就预防艾滋病毒母婴传播的B方案策略的安全性而言,这些发现令人放心。

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