Spectrum of Non-Nucleoside Reverse Transcriptase Inhibitor-Associated Drug Resistance Mutations in Persons Living with HIV-1 Receiving Rilpivirine.

IF 3.8 3区医学 Q2 VIROLOGY

Viruses-Basel Pub Date : 2024-10-31 DOI:10.3390/v16111715

Pavithra Nagarajan, Jinru Zhou, Giulia Di Teodoro, Francesca Incardona, Carole Seguin-Devaux, Rolf Kaiser, Ana B Abecasis, Perpetua Gomes, Kaiming Tao, Maurizio Zazzi, Robert W Shafer

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引用次数: 0

Abstract

Introduction: Few data are currently available on the nonnucleoside reverse transcriptase (RT) inhibitors (NNRTI) resistance mutations selected in persons living with HIV-1 (PLWH) who develop virological failure while receiving rilpivirine (RPV).

Methods: We analyzed pooled HIV-1 RT genotypic data from 280 PLWH in the multicenter EuResist database and 115 PLWH in the Stanford HIV Drug Resistance Database (HIVDB) who received RPV as their only NNRTI.

Results: Among the 395 PLWH receiving RPV, 180 (45.6%) had one or more NNRTI-associated DRMs. Overall, 44 NNRTI-associated DRMs were identified, including 26 that occurred in two or more PLWHs. Seven mutations had a prevalence ≥10% among the 180 PLWH with one or more NNRTI-associated DRM: E138K (32.2%), V90I (25.0%), K101E (17.8%), Y181C (17.2%), E138A (13.9%), H221Y (12.2%), and K103N (10.6%). Y181C was significantly more likely to co-occur with K101E, V179F, H221Y, and M230L. Ten novel non-polymorphic mutations at known NNRTI-associated mutation positions were also identified, usually in just one PLWH: L100F, V108A, T139I, P225S, M230V, Y232C, and T240A/I/M/S.

Conclusions: Our analysis extends the spectrum of mutations emerging in PLWH receiving RPV. Additional phenotypic characterization of RPV-selected mutations is necessary to better understand their biological and possible clinical significance.

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接受利匹韦林治疗的 HIV-1 感染者中与非核苷逆转录酶抑制剂相关的耐药性突变谱。

导言：目前关于在接受利匹韦林（RPV）治疗期间出现病毒学失败的 HIV-1 感染者（PLWH）中选择的非核苷类逆转录酶（RT）抑制剂（NNRTI）耐药性突变的数据很少：我们分析了多中心EuResist数据库中280名PLWH和斯坦福HIV耐药数据库（HIVDB）中115名接受RPV作为唯一NNRTI的PLWH的HIV-1 RT基因型数据：在接受 RPV 治疗的 395 名 PLWH 中，180 人（45.6%）患有一种或多种与 NNRTI 相关的 DRM。总共发现了 44 种 NNRTI 相关 DRM，其中 26 种发生在两名或两名以上 PLWH 身上。在 180 名出现一种或多种 NNRTI 相关 DRM 的 PLWH 中，有七种突变的发生率≥10%：E138K（32.2%）、V90I（25.0%）、K101E（17.8%）、Y181C（17.2%）、E138A（13.9%）、H221Y（12.2%）和 K103N（10.6%）。Y181C与K101E、V179F、H221Y和M230L同时出现的几率明显更高。在已知的 NNRTI 相关突变位点上还发现了 10 个新的非多态性突变，这些突变通常只发生在一名 PLWH 身上：L100F、V108A、T139I、P225S、M230V、Y232C 和 T240A/I/M/S：我们的分析扩大了接受 RPV 的 PLWH 中出现的突变范围。为了更好地了解这些突变的生物学意义和可能的临床意义，有必要对 RPV 挑选出的突变进行更多的表型鉴定。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Viruses-Basel VIROLOGY-

CiteScore

7.30

自引率

12.80%

发文量

2445

审稿时长

1 months

期刊介绍： Viruses (ISSN 1999-4915) is an open access journal which provides an advanced forum for studies of viruses. It publishes reviews, regular research papers, communications, conference reports and short notes. Our aim is to encourage scientists to publish their experimental and theoretical results in as much detail as possible. There is no restriction on the length of the papers. The full experimental details must be provided so that the results can be reproduced. We also encourage the publication of timely reviews and commentaries on topics of interest to the virology community and feature highlights from the virology literature in the ''News and Views'' section. Electronic files or software regarding the full details of the calculation and experimental procedure, if unable to be published in a normal way, can be deposited as supplementary material.