Full-Spectrum Surveillance of Pre-Treatment HIV Drug Resistance in Southeastern China

Pharmaceuticals Pub Date : 2024-07-06 DOI:10.3390/ph17070900
Jiafeng Zhang, Baochang Sun, Zihang Sheng, X. Ding, Q. Fan, Gang Huang, Zhi-hong Guo, Ping Zhong, L. Liao, Hui Xing, Yan Xia, C. Chai, Jianmin Jiang
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Abstract

HIV drug resistance compromises the ability of anti-retroviral therapy (ART) to suppress viral replication, resulting in treatment failure. This study investigates the prevalence of pre-treatment drug resistance (PDR) in newly diagnosed individuals in a prosperous city (Wenzhou) in Southeastern China. A cross-sectional investigation was carried out among 473 newly diagnosed ART-naive HIV-1-infected individuals between January and December 2022. The protease–reverse transcriptase (PR-RT) region and integrase (IN) region of HIV-1 were amplified by two separately nested PCRs, followed by sequencing. Drug resistance mutations (DRMs) and drug resistance to nucleoside reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), protease inhibitors (PIs) and integrase strand transfer inhibitors (INSTIs) were analyzed. The PDR prevalence was 6.5% [95% CI: 4.4–9.1] for any anti-retroviral drug, 0.9% [95% CI: 0.3–2.3] for NRTIs, 4.1% [95% CI: 2.5–6.5] for NNRTIs, 1.8% [95% CI: 0.8–3.6] for PIs and 0.5% [95% CI: 0.1–1.8] for INSTIs. According to the subtyping results of the PR-RT region, 11 different subtypes and 31 unique recombinant forms (URFs) were found. CRF07_BC was the dominant subtype (53.7%, 233/434), followed by CRF01_AE (25.3%, 110/434). V179D (1.6%) and K103N (1.4%) were the most predominant types of NNRTI DRMs. Q58E (1.2%) and M184V (0.7%) were the most frequent PI DRMs and NRTI DRMs, respectively. The INSTI-related DRMs Y143S (causes high-level resistance to RAL) and G163K (causes low-level resistance to EVG and RAL) were found in one patient each. Given the relatively high PDR prevalence of NNRTI (4.1%), non-NNRTI-based ART may be preferred in the future. It is recommended to include genotypic resistance testing before starting ART in regions where feasible.
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中国东南地区艾滋病治疗前耐药性的全谱监测
艾滋病耐药性会损害抗逆转录病毒疗法(ART)抑制病毒复制的能力,导致治疗失败。本研究调查了中国东南部繁华城市(温州)新确诊患者治疗前耐药性(PDR)的发生率。本研究对 2022 年 1 月至 12 月间新确诊的 473 例抗逆转录病毒疗法(ART)免疫艾滋病病毒(HIV-1)感染者进行了横断面调查。通过两次分别嵌套的PCR扩增HIV-1的蛋白酶逆转录酶(PR-RT)区和整合酶(IN)区,然后进行测序。分析了耐药性突变(DRMs)以及对核苷酸逆转录酶抑制剂(NRTIs)、非核苷酸逆转录酶抑制剂(NNRTIs)、蛋白酶抑制剂(PIs)和整合酶链转移抑制剂(INSTIs)的耐药性。任何抗逆转录病毒药物的 PDR 发生率为 6.5% [95% CI:4.4-9.1],NRTIs 为 0.9% [95% CI:0.3-2.3],NNRTIs 为 4.1% [95% CI:2.5-6.5],PIs 为 1.8% [95% CI:0.8-3.6],INSTIs 为 0.5% [95% CI:0.1-1.8]。根据 PR-RT 区域的亚型分析结果,发现了 11 种不同的亚型和 31 种独特的重组形式 (URF)。CRF07_BC 是主要亚型(53.7%,233/434),其次是 CRF01_AE(25.3%,110/434)。V179D(1.6%)和 K103N(1.4%)是最主要的 NNRTI DRMs 类型。Q58E(1.2%)和 M184V(0.7%)分别是最常见的 PI DRM 和 NRTI DRM。与 INSTI 相关的 DRM Y143S(导致对 RAL 的高水平耐药)和 G163K(导致对 EVG 和 RAL 的低水平耐药)各在一名患者中发现。鉴于 NNRTI 的 PDR 发生率相对较高(4.1%),未来可能首选基于非 NNRTI 的抗逆转录病毒疗法。建议在可行的地区,在开始抗逆转录病毒疗法之前进行基因型耐药性检测。
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