整合酶抑制剂耐药相关突变与 HIV 感染孕妇。

Integrase strand transfer inhibitors resistance-associated mutations in HIV-infected pregnant women.

机构信息

Diego Cecchini, Infectious Diseases Unit, Hospital Cosme Argerich, Almirante Brown 240, Buenos Aires 1155AHD, Argentina.

出版信息

Rev Esp Quimioter. 2024 Dec;37(6):479-485. doi: 10.37201/req/074.2024. Epub 2024 Oct 4.

DOI:10.37201/req/074.2024

PMID:39364596

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11578435/

Abstract

OBJECTIVE

To date, no data exist regarding the prevalence of integrase inhibitor (INSTI) resistance-associated mutations (HIVDRM) in HIV-infected pregnant women (HPW) in Latin America. We describe the prevalence and transmissibility of integrase HIVDRM in a historical cohort of INSTI-naïve HPW from Argentina (n=56) with Next Generation Sequencing (NGS).

METHODS

Bioinformatics analysis was performed by HyDRA software for 20%, 10%, 5%, 2%, and 1% sensitivity thresholds. We calculated the mutational viral load for each INSTI-HIVDRM, considering those with >1000 c/mL as of high risk of transmissibility.

RESULTS

The predominant HIV subtype was BF (78.5%). Major HIVDRM were not detected with the population sequencing 20% filter. With a 1% threshold, the prevalence increased to 8.9%; Y143C/S, E92G, E138K, and T66I mutations were found. The median (range) mutational load (expressed in c/mL) was: 355 (50.2-11705); with only 1 case >1000 c/mL Accessory mutations (G163R/K, T97A) were detected mostly with a 20% sensitivity threshold with an overall prevalence of 23.2%; the median (IQR) mutational load was: 23929 (4009-63158) c/mL; all of them above 1000 c/mL.

CONCLUSIONS

Our results show evidence of the presence of major INSTI-HIVDRM as aleatory mutations and a high frequency of accessory mutations with potential transmissibility in HPW.

摘要

目的

迄今为止，拉丁美洲尚无关于感染艾滋病毒的孕妇（HPW）中整合酶抑制剂（INSTI）耐药相关突变（HIVDRM）流行率的数据。我们通过下一代测序（NGS）描述了来自阿根廷的初始未使用 INSTI 的 HIVDRM 流行率和整合酶 HIVDRM 的传染性。

方法

HyDRA 软件对 20%、10%、5%、2%和 1%的灵敏度阈值进行了生物信息学分析。我们考虑到每个 INSTI-HIVDRM 的突变病毒载量> 1000 c/mL 具有高传播风险，计算了每个 INSTI-HIVDRM 的突变病毒载量。

结果

主要的 HIV 亚型是 BF（78.5%）。人群测序 20%的过滤器未检测到主要的 HIVDRM。使用 1%的阈值，流行率增加到 8.9%；发现 Y143C/S、E92G、E138K 和 T66I 突变。中位（范围）突变负荷（以 c/mL 表示）为：355（50.2-11705）；只有 1 例> 1000 c/mL。发现了主要的辅助突变（G163R/K、T97A），主要在 20%的灵敏度阈值下检测到，总流行率为 23.2%；中位（IQR）突变负荷为：23929（4009-63158）c/mL；所有都超过了 1000 c/mL。