喀麦隆 HIV-1 各亚型中整合酶耐药突变和保守区的基线情况：对资源有限环境中向多替拉韦转换的影响。

Baseline integrase drug resistance mutations and conserved regions across HIV-1 clades in Cameroon: implications for transition to dolutegravir in resource-limited settings.

机构信息

Virology Laboratory, Chantal BIYA International Reference Centre for Research on HIV/AIDS Prevention and Management (CIRCB), Yaoundé, Cameroon.

Department of Experimental Medicine, University of Rome "Tor Vergata", Rome, Italy.

出版信息

J Antimicrob Chemother. 2021 Apr 13;76(5):1277-1285. doi: 10.1093/jac/dkab004.

DOI:10.1093/jac/dkab004

PMID:33501504

Abstract

BACKGROUND

Transition to dolutegravir-based regimens in resource-limited settings (RLS) requires prior understanding of HIV-1 integrase variants and conserved regions. Therefore, we evaluated integrase drug resistance mutations (DRMs) and conserved regions amongst integrase strand transfer inhibitor (INSTI)-naive patients harbouring diverse HIV-1 clades in Cameroon.

METHODS

A cross-sectional study was conducted amongst 918 INSTI-naive patients from Cameroon (89 ART-naive and 829 ART-experienced patients). HIV-1 sequences were interpreted regarding INSTI-DRMs using the Stanford HIVdb v8.9-1 and the 2019 IAS-USA list. Amino acid positions with <1% variability were considered as highly conserved. Subtyping was performed by phylogeny.

RESULTS

Overall prevalence (95% CI) of INSTI-DRMs was 0.8% (0.4-1.7), with 0.0% (0.0-4.0) amongst ART-naive versus 0.9% (0.5-1.9) amongst ART-experienced patients; P = 0.44. Accessory mutations (95% CI) were found in 33.8% (30.9-37.0), with 38.2% (28.1-49.1) amongst ART-naive versus 33.4% (30.4-36.7) amongst ART-experienced patients; P = 0.21. Of 288 HIV-1 integrase amino acid positions, 58.3% were highly conserved across subtypes in the following major regions: V75-G82, E85-P90, H114-G118, K127-W132, E138-G149, Q168-L172, T174-V180, W235-A239 and L241-D253. Wide genetic diversity was found (37 clades), including groups M (92.3%), N (1.4%), O (6.2%) and P (0.1%). Amongst group M, CRF02_AG was predominant (47.4%), with a significantly higher frequency (95% CI) of accessory mutations compared with non-AG [41.4% (36.8-46.0) versus 27.1% (23.3-31.2) respectively; P < 0.001].

CONCLUSIONS

The low baseline of INSTI-DRMs (<1%) in Cameroon suggests effectiveness of dolutegravir-based regimens. In spite of high conservation across clades, the variability of accessory mutations between major circulating strains underscores the need for monitoring the selection of INSTI-DRMs while scaling up dolutegravir-based regimens in RLS.

摘要

背景

在资源有限的环境（RLS）中转换为多替拉韦为基础的方案需要事先了解 HIV-1 整合酶的变异体和保守区域。因此，我们评估了在喀麦隆的 HIV-1 整合酶抑制剂（INSTI）初治患者中，不同 HIV-1 群系中整合酶耐药突变（DRMs）和保守区域。

方法

在喀麦隆进行了一项横断面研究，共纳入了 918 例初治 INSTI 的患者（89 例 ART 初治和 829 例 ART 经验丰富的患者）。使用斯坦福 HIVdb v8.9-1 和 2019 年 IAS-USA 列表，对 INSTI-DRMs 进行了 HIV-1 序列解释。变异率<1%的氨基酸位置被认为是高度保守的。通过系统发生学进行亚型分类。

结果

总体而言，INSTI-DRMs 的流行率（95%CI）为 0.8%（0.4-1.7），ART 初治患者为 0.0%（0.0-4.0），ART 经验丰富患者为 0.9%（0.5-1.9）；P=0.44。发现了辅助突变（95%CI），占 33.8%（30.9-37.0），ART 初治患者为 38.2%（28.1-49.1），ART 经验丰富患者为 33.4%（30.4-36.7）；P=0.21。在 288 个 HIV-1 整合酶氨基酸位置中，58.3%在主要区域高度保守，包括 V75-G82、E85-P90、H114-G118、K127-W132、E138-G149、Q168-L172、T174-V180、W235-A239 和 L241-D253。发现了广泛的遗传多样性（37 个群系），包括 M 群（92.3%）、N 群（1.4%）、O 群（6.2%）和 P 群（0.1%）。在 M 群中，CRF02_AG 占主导地位（47.4%），与非 AG 相比，辅助突变的频率显著更高[41.4%（36.8-46.0）与 27.1%（23.3-31.2）；P<0.001]。