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.
J Antimicrob Chemother. 2021 Apr 13;76(5):1277-1285. doi: 10.1093/jac/dkab004.
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.
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.
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].
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.
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。
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。
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]。
喀麦隆 INSTI-DRMs 的基线水平较低（<1%），这表明多替拉韦为基础的方案有效。尽管在群系之间有高度的保守性，但主要流行株之间辅助突变的变异性强调了在资源有限的环境中扩大多替拉韦为基础的方案时，需要监测整合酶耐药突变的选择。
