抗逆转录病毒治疗初治和经治 HIV-1 感染人群中可能与卡替拉韦/利匹韦林失败相关的基因型因素的频率。

Frequency of genotypic factors possibly associated with cabotegravir/rilpivirine failure in antiretroviral treatment-naïve and -experienced HIV-1- infected population.

机构信息

Pomeranian Medical University in Szczecin, Department of Infectious, Tropical Diseases and Immune Deficiency, Poland.

出版信息

Infect Genet Evol. 2022 Oct;104:105358. doi: 10.1016/j.meegid.2022.105358. Epub 2022 Aug 31.

DOI:10.1016/j.meegid.2022.105358

PMID:36057423

Abstract

OBJECTIVES

The long-acting injectable (LAI) cabotegravir (CAB) and rilpivirine (RPV) treatment offers important advantages over oral ART (antiretroviral therapy), however baseline factors possibly contributing to the CAB/RPV treatment failure were identified. The purpose of this study was to describe the frequency of virologic factors previously influencing efficacy of this treatment, namely RPV and CAB resistance-associated mutations (RAMs) and A1/A6 subtype among naïve and treatment-experienced HIV-1-infected patients from Poland.

METHODS

The following datasets of HIV-1 sequences were analysed: 4809 protease and reverse transcriptase (PR/RT) sequences obtained from 4649 Polish Caucasian patients (4122 naive and 687 non-naïve) supplemented with integrase (PR/RT/INT) sequences in 1217 cases (942 naïve and 275 non-naïve). Sub-subtypes A were assigned by phylogenetic methods. Major and minor CAB and RPV RAMs were determined according to the IAS-USA 2019 list, while minor RAMs were additionally defined based on the Stanford database algorithm.

RESULTS

Subtype A1/A6 frequency ranged from 6.11% in ART failing cases with PR/RT sequences only, to 15.92% for the PR/RT/INT treatment-naïve dataset, while RPV RAMs were found in up to 5.89% of treatment-naïve and 14.56% of ART failing cases. Regardless treatment history, only <1% sequences had combination of two factors (RPV RAMs and A1/A6 subtype). Furthermore, CAB RAMs were found in 1.27% of treatment-naïve and 14.54% of experienced patients.

CONCLUSIONS

Despite notable frequency of subtype A1/A6 or CAB/RPV RAMs analysed separately, combination of at least two factors previously associated with failure or this treatment is rare. As subtype A1/A6 becomes more common across real-life cohorts continued subtyping and RAM screening will remain of key importance for LAI treatment implementation. Sequence data from this article have been deposited in GenBank under accession numbers: GU906860, GU906864, GU906871-GU906874, JQ305750-JQ305791, KC409134-KC409222, KM057341-KM057362, KM283892-KM284490, KT340108-KT340205, MZ468643-MZ468894, MZ671788-MZ671823, OP298017-OP302727.

摘要

目的

长效注射剂（LAI）卡替拉韦（CAB）和利匹韦林（RPV）治疗与口服抗逆转录病毒疗法（ART）相比具有重要优势，但确定了可能导致 CAB/RPV 治疗失败的基线因素。本研究的目的是描述先前影响该治疗疗效的病毒学因素的频率，即在波兰的 HIV-1 感染的初治和治疗经验患者中，利匹韦林和卡替拉韦耐药相关突变（RAM）和 A1/A6 亚型。

方法

分析了以下 HIV-1 序列数据集：4809 个蛋白酶和逆转录酶（PR/RT）序列来自 4649 名波兰白种人患者（4122 名初治和 687 名非初治），补充了 1217 例整合酶（PR/RT/INT）序列（942 名初治和 275 名非初治）。亚亚型 A 通过系统发育方法确定。主要和次要 CAB 和 RPV RAM 根据 IAS-USA 2019 列表确定，而次要 RAM 则根据斯坦福数据库算法另外定义。

结果

仅在具有 PR/RT 序列的 ART 失败病例中，A1/A6 亚型的频率范围为 6.11%，而在 PR/RT/INT 治疗初治的数据集则为 15.92%，而利匹韦林 RAM 在高达 5.89%的初治和 14.56%的 ART 失败病例中发现。无论治疗史如何，只有不到 1%的序列存在两种因素（RPV RAM 和 A1/A6 亚型）的组合。此外，在初治和有治疗经验的患者中，分别有 1.27%和 14.54%的序列存在 CAB RAM。

结论

尽管分别分析了 A1/A6 亚型或 CAB/RPV RAM 的频率显著，但与该治疗失败或该治疗相关的至少两种因素的组合很少见。随着现实生活队列中 A1/A6 亚型的流行程度不断提高，持续的亚型分类和 RAM 筛查将仍然是 LAI 治疗实施的关键。本文的序列数据已在 GenBank 中以以下登录号提交：GU906860、GU906864、GU906871-GU906874、JQ305750-JQ305791、KM057341-KM057362、KM283892-KM284490、KT340108-KT340205、MZ468643-MZ468894、MZ671788-MZ671823、OP298017-OP302727。