Department of Biological and Biomedical Sciences, Aga Khan University, Karachi, Pakistan.
Department of Genetics, University of Karachi, Karachi, Pakistan.
PLoS One. 2023 Aug 24;18(8):e0290425. doi: 10.1371/journal.pone.0290425. eCollection 2023.
Antiretroviral therapy (ART) effectiveness is compromised by the emergence of HIV drug resistance mutations (DRM) and can lead to the failure of ART. Apart from intrinsic viral factors, non-compliance with drugs and/or the use of sub-optimum therapy can lead to the emergence of DRMs. In Pakistan HIV currently exists as a concentrated epidemic, however, ART coverage is very low, and drug adherence is poor. ART is selected assuming without baseline genotyping. Pakistan has recently seen a rise in treatment failures, but the country's actual burden of DRM is still unknown. In this study, we perform the genetic and drug resistance analysis of the pol gene from Pakistani HIV-positive ART-naïve and ART-experienced individuals.
In this study, HIV-1 pol was sequenced from 146 HIV-1 positive individuals, divided into ART-naïve (n = 37) and ART-experienced (n = 109). The sequences were also used to determine HIV-1 subtypes, the prevalence of DRM, and pol genetic variability.
DRM analysis identified numerous DRMs against reverse transcriptase inhibitors in both ART-naïve and ART-experienced groups, including a few that are classified as rare. Additionally, the ART-experienced group showed mutations associated with resistance to protease inhibitors. Genetic analysis showed negative selection pressure in both groups, but a higher rate of evolution in the ART-naïve group.
High prevalence of DRMs, especially against previous first-line treatment in ART- naïve and the accumulation of DRMs in ART-experienced groups is concerning and warrants that a more extensive DRM survey be carried out to inform first-line and second-line ART regimen recommendations.
抗逆转录病毒疗法 (ART) 的疗效受到 HIV 耐药突变 (DRM) 的影响，可能导致 ART 失败。除了内在的病毒因素外，不遵守药物规定和/或使用次优治疗也会导致 DRM 的出现。在巴基斯坦，HIV 目前呈集中流行，但 ART 覆盖率非常低，药物依从性也很差。ART 的选择是在没有基线基因分型的情况下进行的。巴基斯坦最近出现了治疗失败的上升，但该国 DRM 的实际负担仍不清楚。在这项研究中，我们对来自巴基斯坦未经 ART 治疗和有 ART 治疗经验的 HIV 阳性个体的 pol 基因进行了遗传和耐药性分析。
在这项研究中，我们对 146 名 HIV-1 阳性个体的 pol 基因进行了测序，将其分为未经 ART 治疗（n=37）和有 ART 治疗经验（n=109）两组。这些序列还用于确定 HIV-1 亚型、DRM 的流行率以及 pol 基因的变异性。
DRM 分析在未经 ART 治疗和有 ART 治疗经验的两组中都发现了针对逆转录酶抑制剂的多种 DRM，包括一些被归类为罕见的 DRM。此外，有 ART 治疗经验的组还显示出与蛋白酶抑制剂耐药相关的突变。遗传分析显示两组都受到负选择压力，但未经 ART 治疗组的进化速度更高。
DRM 的高流行率，尤其是在未经 ART 治疗的患者中对先前一线治疗的耐药，以及在有 ART 治疗经验的患者中 DRM 的积累令人担忧，这需要进行更广泛的 DRM 调查，以告知一线和二线 ART 方案的建议。
