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2021 - 2023年意大利西西里岛HIV感染者中HIV-1亚型的下一代测序与耐药突变

Next-generation sequencing and drug resistance mutations of HIV-1 subtypes in people living with HIV in Sicily, Italy, 2021-2023.

作者信息

Pipitò Luca, Trizzino Marcello, Mascarella Chiara, Cannella Sara, Gaudiano Roberta, Ganci Irene, D'Alessandro Gaetano, Romanin Benedetta, Santoro Maria Mercedes, Giammanco Giovanni M, Cascio Antonio, Bonura Celestino

机构信息

Department of Health Promotion, Mother and Child Care, Internal Medicine, and Medical Specialties "G D'Alessandro," University of Palermo, Palermo, Italy; Infectious and Tropical Diseases Unit and Sicilian Regional Reference Center for the fight against AIDS, AOU Policlinico "P. Giaccone," Palermo, Italy; Palermo Fast-Track City, Casa dei Diritti, Palermo, Italy.

Infectious and Tropical Diseases Unit and Sicilian Regional Reference Center for the fight against AIDS, AOU Policlinico "P. Giaccone," Palermo, Italy; Palermo Fast-Track City, Casa dei Diritti, Palermo, Italy.

出版信息

J Glob Antimicrob Resist. 2025 Mar;41:68-76. doi: 10.1016/j.jgar.2024.12.015. Epub 2024 Dec 27.

Abstract

OBJECTIVES

HIV-1 infection continues to be a significant public health concern, notwithstanding the expanded utilization of antiretroviral treatment (ART), due to the emergence of drug resistance. The prevalence of transmitted drug resistance remains uncertain, particularly concerning integrase inhibitors. This study aimed to assess the extent of HIV resistance in both ART-naïve and experienced individuals living with HIV (PLHIV) at the University Hospital in Palermo, Italy.

METHODS

Genotyping and mutation analysis were performed on ART naïve and experienced PLHIV admitted from June 2021 to October 2023 by the NGS method. Mutations were detected by testing different NGS frequency cut-offs: ≥5 %, ≥10 %, and ≥20 %. Demographic, clinical, virological, and immunological data were retrospectively collected.

RESULTS

Of the PLHIV, 85 (70 %) were ART-naïve, while 36 (30 %) were ART-experienced with virological failure. The main HIV-1 subtype was B (54 %), which was significantly associated with Italy-born (P < 0.001) and experienced PLHIV (P = 0.024). In the remaining cases, A1 (6 %), C (3 %), F1 (7 %), G (2 %), and Circulating Recombinant Forms (28 %) were reported. At least one mutation for a drug class was detected in 39.7 %, 45.4 %, and 53.7 % of cases at HIV-1 NGS thresholds of 20 %, 10 %, and 5 %, respectively. Drug resistance was found in 18.2 %, 25.6 %, and 33.0 %, by NGS cut-off of 20 %, 10 %, and 5 % respectively. The lowering of NGS cut-offs mainly increased the rates of integrase strand transfer inhibitor resistance. For overall resistance, no difference was observed between B and non-B subtypes for any NGS cut-offs.

摘要

目的

尽管抗逆转录病毒治疗(ART)的使用有所扩大,但由于耐药性的出现,HIV-1感染仍然是一个重大的公共卫生问题。传播性耐药的流行情况仍不确定,尤其是关于整合酶抑制剂方面。本研究旨在评估意大利巴勒莫大学医院初治和经治的HIV感染者(PLHIV)中HIV耐药的程度。

方法

采用二代测序(NGS)方法,对2021年6月至2023年10月收治的初治和经治PLHIV进行基因分型和突变分析。通过检测不同的NGS频率截断值(≥5%、≥10%和≥20%)来检测突变。回顾性收集人口统计学、临床、病毒学和免疫学数据。

结果

在PLHIV中,85例(70%)为初治患者,36例(30%)为经治且病毒学失败的患者。主要的HIV-1亚型为B型(54%),这与在意大利出生的患者(P<0.001)和经治PLHIV(P = 0.024)显著相关。在其余病例中,报告了A1型(6%)、C型(3%)、F1型(7%)、G型(2%)和循环重组型(28%)。在HIV-1 NGS阈值为20%、10%和5%时,分别有39.7%、45.4%和53.7%的病例检测到至少一种针对某类药物的突变。通过NGS截断值分别为20%、10%和5%检测发现,耐药率分别为18.2%、25.6%和33.0%。NGS截断值的降低主要增加了整合酶链转移抑制剂耐药率。对于总体耐药情况,在任何NGS截断值下,B型和非B型亚型之间均未观察到差异。

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