Institute of Virology, Leipzig University, Leipzig, Germany; Department of Medical Microbiology, School of Biomedical and Laboratory Sciences, University of Gondar, Gondar, Ethiopia.
J Med Virol. 2015 Jun;87(6):978-84. doi: 10.1002/jmv.24110. Epub 2015 Feb 3.
Antiretroviral drug resistance is a major challenge for management and control of HIV-1 infection worldwide and particularly in resource limited countries. The frequency of primary drug resistance mutations (DRMs) and of naturally occurring polymorphisms was determined in 83 antiretroviral treatment (ART) naïve Ethiopian individuals infected with HIV-1, consecutively enrolled in 2010. In all individuals HIV-1C was found. The median (interquartile range) of CD4(+) T-cell count and viral load were 100 (49-201) cells/μl and 44,640 (12,553-134,664) copies/ml, respectively. Protease (PR) and reverse transcriptase (RT) genes of HIV-1 RNA were amplified and sequenced. The proportion of primary DRM to any drug class, using the World Health Organization mutation lists, was 7.2% (6/83), thus exceeding the WHO threshold limit of 5%. Three individuals (3.6%) had non-nucleoside reverse transcriptase inhibitor (NNRTI) mutations, two individuals (2.4%) had protease inhibitor mutations, and one (1.2%) had mutations associated with two drug classes (nucleoside reverse transcriptase inhibitor and NNRTI). In addition, the frequency of polymorphisms in the PR and RT genes was higher compared with previous studies in Ethiopian as well as worldwide isolates. Hence, genotypic drug resistance testing as part of routine management of individuals seems reasonable even in resource limited countries prior to treatment in order to allow proper choice of ART.
抗逆转录病毒药物耐药性是全球,特别是资源有限国家管理和控制 HIV-1 感染的主要挑战。在 2010 年连续入组的 83 例未曾接受过抗逆转录病毒治疗(ART)的埃塞俄比亚 HIV-1 感染者中,测定了原发性耐药突变(DRM)和天然发生的多态性的频率。所有个体均发现 HIV-1C。CD4+T 细胞计数和病毒载量的中位数(四分位数间距)分别为 100(49-201)细胞/μl 和 44640(12553-134664)拷贝/ml。扩增和测序了 HIV-1 RNA 的蛋白酶(PR)和逆转录酶(RT)基因。使用世界卫生组织的突变列表,原发性 DRM 对任何药物类别的比例为 7.2%(6/83),超过了世卫组织 5%的阈值限制。有 3 名(3.6%)个体存在非核苷类逆转录酶抑制剂(NNRTI)突变,2 名(2.4%)个体存在蛋白酶抑制剂突变,1 名(1.2%)个体存在与两种药物类别(核苷类逆转录酶抑制剂和 NNRTI)相关的突变。此外,与之前在埃塞俄比亚以及全球分离株的研究相比,PR 和 RT 基因中的多态性频率更高。因此,即使在资源有限的国家,在开始治疗之前,作为个体常规管理的一部分,进行基因型耐药性检测以合理选择 ART 似乎是合理的。