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儿童病毒学失败时垂直传播 HIV-1 毒株的基因的分子特征。

Molecular Characterization of the Gene of Vertically Transmitted HIV-1 Strains in Children with Virological Failure.

机构信息

ICMR-National Institute for Research in Tuberculosis, Chennai, India.

Division of Microbiology/Infectious Diseases Unit, St. Johns Research Institute, Bangalore, India.

出版信息

AIDS Res Hum Retroviruses. 2022 Jun;38(6):491-496. doi: 10.1089/AID.2021.0227. Epub 2022 May 16.

Abstract

HIV-1 gene sequences were analyzed from 77 HIV-1 positive children infected perinatally and exhibiting virological failure (VF). Viral subtyping, phylogenetic analysis, and genotypic drug resistance analysis were carried out on samples collected before start of anti retroviral treatment (ART) (baseline, BL), and at 12 months post-ART initiation (M12). Subtype C was found to be most predominant, seen in 75 of the 77 (97.4%) children. The level of pretreatment drug resistance (PDR) was 14% among these children. At BL, K103N (5), E138A/G (4), and M184V (3) were the most common mutations. At M12 the prevalence of any resistance-associated mutation (RAM) (acquired drug resistance/ADR) was 81.8% (63/77). Dual class resistance mutations were seen in 64% (49/77) of children. M184V/I, K103N/S, and Y181C were the most commonly occurring mutations, seen in 76%, 51%, and 36% children. RAMs to the second-generation non-nucleoside reverse transcriptase inhibitors (NNRTI), etravirine (ETR) and rilpivirine (RPV), were seen in 40.2% (31/77) and 48.05% (37/77) of the children, respectively. Our findings reveal similar prevalence rates of PDR and ADR in children with VF as reported in other studies. Occurrence of ETR and RPV resistance associated mutations (RAMs) is of concern and highlights the need for timely switch of regimens guided by genotypic resistance testing in perinatally infected children from India.

摘要

对 77 例经围产期感染、出现病毒学失败 (VF) 的 HIV-1 阳性儿童的 HIV-1 基因序列进行了分析。在开始抗逆转录病毒治疗 (ART) 之前 (基线,BL) 和启动 ART 后 12 个月 (M12) 采集样本,进行病毒亚型分析、系统进化分析和基因型耐药性分析。77 例儿童中,75 例 (97.4%) 为 C 型。这些儿童中,预处理耐药率 (PDR) 为 14%。BL 时,最常见的突变是 K103N (5)、E138A/G (4) 和 M184V (3)。M12 时,任何耐药相关突变 (RAM) (获得性耐药/ADR) 的流行率为 81.8% (63/77)。64% (49/77) 的儿童出现双耐药突变。76%、51%和 36%的儿童出现 M184V/I、K103N/S 和 Y181C 最常见的突变。40.2% (31/77) 和 48.05% (37/77) 的儿童出现对第二代非核苷类逆转录酶抑制剂 (NNRTI) 依曲韦林 (ETR) 和利匹韦林 (RPV) 的耐药相关突变 (RAM)。我们的研究结果显示,在印度围产期感染的儿童中,VF 患者的 PDR 和 ADR 发生率与其他研究相似。出现 ETR 和 RPV 耐药相关突变 (RAM) 令人担忧,强调需要及时根据基因型耐药性检测,为印度围产期感染的儿童转换治疗方案。

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