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在毛里塔尼亚,接受治疗的成人 1 型人类免疫缺陷病毒感染者的耐药突变和遗传多样性。

Drug resistance mutations and genetic diversity in adults treated for HIV type 1 infection in Mauritania.

机构信息

Laboratory of Virology, Public Health National Institute (INRSP), Nouakchott, Mauritania.

出版信息

J Med Virol. 2014 Mar;86(3):404-10. doi: 10.1002/jmv.23860. Epub 2013 Dec 7.

Abstract

The aim of this cross-sectional study was to evaluate the drug resistance mutationprofile observed in patients receiving antiretroviral therapy with virological failure and to document the HIV-1 genetic diversity in Mauritania. Eighty-six subjects were included and 65 samples were amplified successfully and sequenced. HIV-1 genotyping was performed using the Agence Nationale de Recherche sur le SIDA AC11 resistance procedure. The median treatment duration was 32 months (range: 6-88) and the median viral load, 5 log10 copies/ml (range: 3.13-7). Fifty-nine patients (90.8%) were on first line regimens including 32.0% (19/59) on triomune fixed-dose and six on second-line therapy with NonNucleoside Reverse Transcriptase plus a protease inhibitor. Forty-seven patients (72.3%) had at least one drug resistance mutation including 73.0% (43/59) on first-line therapy. For the second-line, one out of six patients presented resistance mutations and only one presented PI DRM. Overall, the most common DRMs detected were M184V/I (n = 32; 49.2%), K103N (n = 28; 43%), and Y181C (n = 13; 20%). Thymidine Analog Mutations (TAMs) were found in 26.0% (n = 17) of strains and the most common was T215Y (n = 11, 16.9%). Phylogenetic analysis revealed 17 HIV-1 variants with the predominance of CRF02_AG (n = 42; 64.6%). A high rate of DRM was found in this study and shows the potential need for a structured virological surveillance including viral load quantification and genotyping. Further studies may also be needed in regards to the great variability of HIV-1 strains in Mauritania.

摘要

本横断面研究旨在评估接受抗逆转录病毒治疗后病毒学失败的患者中观察到的耐药突变谱,并记录毛里塔尼亚的 HIV-1 遗传多样性。共纳入 86 例患者,成功扩增并测序 65 例样本。使用 Agence Nationale de Recherche sur le SIDA AC11 耐药程序进行 HIV-1 基因分型。中位治疗时间为 32 个月(范围:6-88),中位病毒载量为 5 log10 拷贝/ml(范围:3.13-7)。59 例患者(90.8%)接受一线治疗方案,其中 32.0%(19/59)接受三联固定剂量,6 例接受二线治疗,包括非核苷类逆转录酶加蛋白酶抑制剂。47 例患者(72.3%)至少有 1 种耐药突变,其中一线治疗患者中有 73.0%(43/59)。二线治疗中,1 例患者出现耐药突变,仅有 1 例患者出现蛋白酶抑制剂耐药突变。总的来说,检测到的最常见耐药突变包括 M184V/I(n = 32;49.2%)、K103N(n = 28;43%)和 Y181C(n = 13;20%)。26.0%(n = 17)的菌株中发现胸苷类似物突变(TAMs),最常见的是 T215Y(n = 11,16.9%)。系统进化分析显示,有 17 种 HIV-1 变异株,以 CRF02_AG 为主(n = 42;64.6%)。本研究发现耐药突变率较高,表明需要进行有组织的病毒学监测,包括病毒载量定量和基因分型。鉴于毛里塔尼亚 HIV-1 株的巨大变异性,可能还需要进一步研究。

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