PDF(Pubmed)
Abstract：
HIV incidence in Kazakhstan increased by 73% between 2010 and 2020, with an estimated 35,000 people living with HIV (PLHIV) in 2020. The development of antiretroviral drug resistance is a major threat to effective antiretroviral therapy (ART), yet studies on the prevalence of drug resistance in Kazakhstan are sparse. In this study on the molecular epidemiology of HIV in Kazakhstan, we analyzed 968 partial HIV-1 pol sequences that were collected between 2017 and 2020 from PLHIV across all regions of Kazakhstan, covering almost 3% of PLHIV in 2020. Sequences predominantly represented subtypes A6 (57%) and CRF02_AG (41%), with 32% of sequences exhibiting high-level drug resistance. We further identified distinct drug-resistant mutations (DRMs) in the two subtypes: subtype A6 showed a propensity for DRMs A62V, G190S, K101E, and D67N, while CRF02_AG showed a propensity for K103N and V179E. Codon usage analysis revealed that different mutational pathways for the two subtypes may explain the difference in G190S and V179E frequencies. Phylogenetic analysis highlighted differences in the timing and geographic spread of both subtypes within the country, with A62V-harboring subtype A6 sequences clustering on the phylogeny, indicative of sustained transmission of the mutation. Our findings suggest an HIV epidemic characterized by high levels of drug resistance and differential DRM frequencies between subtypes. This emphasizes the importance of drug resistance monitoring within Kazakhstan, together with DRM and subtype screening at diagnosis, to tailor drug regimens and provide effective, virally suppressive ART.
摘要：
在2010年至2020年期间，哈萨克斯坦的艾滋病毒发病率增加了73％，到2020年估计有35,000人感染艾滋病毒（PLHIV）。抗逆转录病毒药物耐药性的发展是有效抗逆转录病毒疗法(ART)的主要威胁,然而，关于哈萨克斯坦耐药率的研究很少。在这项关于哈萨克斯坦艾滋病毒分子流行病学的研究中，我们分析了2017年至2020年从哈萨克斯坦所有地区的PLHIV中收集的968个部分HIV-1pol序列，到2020年，几乎占PLHIV的3%。序列主要代表亚型A6（57％）和CRF02_AG（41％），32%的序列表现出高水平的耐药性。我们进一步确定了两种亚型中不同的耐药突变（DRMs）：A6亚型显示出DRMsA62V的倾向，G190S,K101E,和D67N,而CRF02_AG显示出K103N和V179E的倾向。密码子使用分析表明，两种亚型的不同突变途径可以解释G190S和V179E频率的差异。系统发育分析强调了这两种亚型在国内的时间和地理分布的差异，带有A62V的A6亚型序列在系统发育上聚类，表明突变的持续传播。我们的发现表明，HIV流行的特征是高水平的耐药性和亚型之间的DRM频率不同。这强调了哈萨克斯坦境内耐药性监测的重要性，在诊断时与DRM和亚型筛查一起，定制药物方案并提供有效的，病毒抑制性艺术。
