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苏里南获得性 HIV-1 耐药性和突变模式的首次评估。

First Assessment of Acquired HIV-1 Drug Resistance and Mutation Patterns in Suriname.

机构信息

"Prof. Dr. Paul C. Flu" Institute for Biomedical Sciences, Paramaribo, Suriname.

Department of Biochemistry, Faculty of Medical Sciences, Anton de Kom Universiteit van Suriname, Paramaribo, Suriname.

出版信息

AIDS Res Hum Retroviruses. 2021 Jul;37(7):557-565. doi: 10.1089/AID.2020.0194. Epub 2021 Jan 12.

Abstract

HIV drug resistance testing is fundamental in clinical patient management, but data on HIV-1 drug-resistant mutations (DRMs) is scarce in the Caribbean and in Suriname limited to one survey on transmitted resistance. The aim of this study was to address this gap, to gain insight in acquired HIV drug resistance (ADR) prevalence and mutation patterns, and to improve HIV-1 treatment outcome of people living with HIV (PLHIV) in Suriname. A prospective cross-sectional study was conducted from July 2018 through January 2019 among treatment-experienced PLHIV ( = 72), with either treatment failure or antiretroviral therapy restart. Genotypic drug resistance testing was performed and DRM impact on drug effectiveness was examined. Genotypic drug resistance testing revealed 97.2% HIV-1 subtype B, 2.8% B/D recombinants and a ADR prevalence of 63.2% in treatment failure patients, with a predominance of nonnucleoside reverse transcriptase inhibitor (NNRTI) mutations. The most common DRMs were M184V (23.6%) and K103N (18.8%). A high level of non-DRM polymorphisms was observed in both the reverse transcriptase (RT) and protease (PR) gene. Interesting deviations from the existing mutation datasets were noted at position E248 and R83 of the RT gene and L63 and V77 in the PR gene. Full susceptibility to all examined drugs was 54.2%, while high-level drug resistance was estimated at 37.5%, which seems promising for treatment outcomes for PLHIV in Suriname, although cross-resistance to next-generation NNRTIs was already estimated for nearly a quarter of the patients. The meager 2.9% of PR DRMs rendered protease inhibitors as an effective rescue HIV-1 treatment.

摘要

HIV 耐药性检测在临床患者管理中至关重要,但加勒比地区和苏里南的 HIV-1 耐药突变 (DRM) 数据很少,仅限于一项关于传播耐药性的调查。本研究旨在填补这一空白,深入了解获得性 HIV 耐药 (ADR) 的流行情况和突变模式,并改善苏里南 HIV 感染者 (PLHIV) 的 HIV-1 治疗效果。一项前瞻性横断面研究于 2018 年 7 月至 2019 年 1 月在治疗经验丰富的 PLHIV 中进行(n=72),这些患者要么治疗失败,要么重新开始抗逆转录病毒治疗。进行了基因型耐药性检测,并检查了 DRM 对药物有效性的影响。基因型耐药性检测显示,97.2%的 HIV-1 亚型为 B,2.8%为 B/D 重组,治疗失败患者的 ADR 患病率为 63.2%,其中以非核苷类逆转录酶抑制剂 (NNRTI) 突变为主。最常见的 DRM 是 M184V(23.6%)和 K103N(18.8%)。在逆转录酶 (RT) 和蛋白酶 (PR) 基因中观察到高水平的非 DRM 多态性。在 RT 基因的 E248 和 R83 以及 PR 基因的 L63 和 V77 位置观察到与现有突变数据集的有趣偏差。所有检测药物的完全敏感性为 54.2%,而高水平耐药性估计为 37.5%,这对苏里南的 PLHIV 治疗结果似乎很有希望,尽管近四分之一的患者已经估计对下一代 NNRTI 有交叉耐药性。PR DRM 的微薄 2.9%使蛋白酶抑制剂成为有效的挽救 HIV-1 治疗方法。

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