Mesh : Humans HIV-1 / genetics drug effects HIV Infections / drug therapy virology Male Drug Resistance, Viral / genetics Female Cross-Sectional Studies Adult Genetic Variation Cabo Verde Middle Aged Phylogeny Anti-HIV Agents / therapeutic use pharmacology Viral Load Young Adult Genotype Mutation Adolescent pol Gene Products, Human Immunodeficiency Virus / genetics

来  源:   DOI:10.1097/QAD.0000000000003866

Abstract:
To characterize the genetic diversity and drug resistance profiles of people with HIV-1 failing ART in Cape Verde (CV).
Cross-sectional study conducted between January 2019 and December 2021 in 24 health centres on the islands of Santiago and São Vicente.
The HIV-1 pol gene was sequenced in individuals with a detectable viral load. HIV-1 genetic diversity was determined by phylogenetic analysis. Drug resistance mutation patterns and resistance phenotypes were estimated using the Stanford algorithm.
Viral load was detected in 73 of 252 (29%) enrolled participants and sequencing data were produced for 58 (79%) participants. CRF02 AG strains predominated (46.5%), followed by subtype G (22.4%). Most patients (80%) had mutations conferring resistance to nonnucleoside reverse transcriptase inhibitors (NNRTIs) (67%), nucleoside reverse transcriptase inhibitors (55%), integrase inhibitors (10%) and/or protease inhibitors (7%) used in Cape Verde, a significant increase compared with a study conducted in 2010-2011. The most common mutations were M184V/I (43%), K103N/S (36%) and G190A/S (19%). NNRTI resistance was associated with younger age and exposure to two or more drug regimens.
The HIV-1 epidemic in Cape Verde is mainly driven by CRF02_AG and subtype G. Resistance to NNRTIs and/or NRTIs is highly prevalent and resistance to LPV/r and DTG is emerging. Our results support the use of DTG-based first-line ART and protease inhibitor-based regimens for patients with virological failure, but emerging resistance to LPV/r and DTG is a concern. Continued monitoring of drug resistance is essential to ensure adequate healthcare for PWH in Cape Verde.
摘要:
目的:确定佛得角抗逆转录病毒治疗失败的HIV-1感染者的遗传多样性和耐药性特征。
方法:2019年1月至2021年12月在圣地亚哥和圣维恩特岛的24个卫生中心进行的横断面研究。
方法:在具有可检测病毒载量的个体中对HIV-1pol基因进行测序。通过系统发育分析确定HIV-1遗传多样性。使用Stanford算法估计耐药突变模式和耐药表型。
结果:252名参与者中有73名(29%)检测到病毒载量,58名(79%)参与者产生了测序数据。CRF02AG菌株占主导地位(46.5%),其次是亚型G(22.4%)。大多数患者(80%)有突变赋予耐药的非核苷逆转录酶抑制剂(NNRTIs)(67%),核苷逆转录酶抑制剂(55%),整合酶抑制剂(10%)和/或蛋白酶抑制剂(7%)用于佛得角,与2010-2011年进行的研究相比,显着增加。最常见的突变为M184V/I(43%),K103N/S(36%)和G190A/S(19%)。NNRTI耐药与年龄较小和暴露于两种或两种以上药物治疗方案有关。
结论:佛得角的HIV-1流行主要由CRF02_AG和G亚型驱动。对NNRTIs和/或NRTIs的耐药性非常普遍,对LPV/r和DTG的耐药性正在出现。我们的结果支持对病毒学失败患者使用基于DTG的一线ART和基于蛋白酶抑制剂的方案,但对LPV/r和DTG的新兴抵抗是一个令人担忧的问题。持续监测耐药性对于确保佛得角PWH的适当医疗保健至关重要。
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