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产后停用三联药物治疗方案后,奈韦拉平和拉米夫定耐药的出现率较低。

Low rate of emergence of nevirapine and lamivudine resistance after post-partum interruption of a triple-drug regimen.

作者信息

Pérez Héctor, Vignoles Moira, Laufer Natalia, Gómez Alejandro, Coll Patricia, Lottner Jorge, Rolón María, Salomón Horacio, Cahn Pedro

机构信息

Fernandes Hospital, Infectious Diseases Unit, Buenos Aires, Argentina.

出版信息

Antivir Ther. 2008;13(1):135-9.

Abstract

INTRODUCTION

Emergence of nevirapine (NVP) resistance may be a consequence of its use in monotherapy to prevent HIV mother-to-child transmission (MTCT). The aim of this study was to evaluate the emergence of strains resistant to NVP and lamivudine (3TC) after discontinuation of antiretroviral therapy (ART) with 3TC/zidovudine (ZDV)/NVP.

METHODS

Twenty pregnant women (ART-naive or preexposed only to ZDV), to whom 3TC/ZDV/NVP was prescribed as MTCT prophylaxis, were studied. They received ART for a median of 4 months with median viral load (VL) at labour <50 copies/ml. Samples were collected between 1 and 15 months (median: 3 months) after ART interruption. Sequence-selective real-time PCR (SPCR), which quantifies minority viral populations containing K103N, Y181C and M184V mutations, and standard genotypic sequencing were assayed.

RESULTS

No mutations associated with resistance to 3TC or NVP were found by standard population sequencing. Analysis of K103N by SPCR showed that 35% of the patients contained < or =0.1% of viruses carrying either the AAC or AAT mutations. For Y181C mutation, 10% of the patients contained <0.5% of viruses with TGT codon change. For M184V mutation, one patient contained 6.2% of virus with GTG mutation and 13 patients (65%) contained <0.9% of mutated viruses. Four women were re-exposed to 3TC/ZDV/NVP and achieved HIV VL <50 copies/ml. No perinatal transmission occurred in any of the 22 births.

CONCLUSIONS

NVP associated with ZDV/3TC as a regimen to prevent MTCT may involve a low risk for the selection of antiretroviral-resistant strains and may not jeopardize the use of these same drugs for future treatment.

摘要

引言

奈韦拉平(NVP)耐药性的出现可能是其用于单药治疗以预防人类免疫缺陷病毒母婴传播(MTCT)的结果。本研究的目的是评估在停用3TC/齐多夫定(ZDV)/NVP抗逆转录病毒疗法(ART)后,对NVP和拉米夫定(3TC)耐药菌株的出现情况。

方法

研究了20名孕妇(初治或仅预先暴露于ZDV),她们被给予3TC/ZDV/NVP作为MTCT预防用药。她们接受ART的中位时间为4个月,分娩时的病毒载量(VL)中位数<50拷贝/ml。在ART中断后1至15个月(中位数:3个月)收集样本。检测了序列选择性实时PCR(SPCR),其可定量含有K103N、Y181C和M184V突变的少数病毒群体,以及标准基因分型测序。

结果

通过标准群体测序未发现与对3TC或NVP耐药相关的突变。通过SPCR对K103N的分析表明,35%的患者携带AAC或AAT突变的病毒占比≤0.1%。对于Y181C突变,10%的患者携带TGT密码子改变的病毒占比<0.5%。对于M184V突变,一名患者携带GTG突变的病毒占6.2%,13名患者(65%)携带的突变病毒占比<0.9%。4名女性再次接受3TC/ZDV/NVP治疗,HIV VL<50拷贝/ml。22次分娩中均未发生围产期传播。

结论

NVP与ZDV/3TC联合作为预防MTCT的方案,可能导致选择抗逆转录病毒耐药菌株的风险较低,并且可能不会影响这些相同药物在未来治疗中的使用。

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