Centro de Investigação em Saúde de Angola (CISA), Caxito, Angola.
Instituto Nacional de Investigação em Saúde (INIS), Luanda, Angola.
Sci Rep. 2024 Jul 10;14(1):15893. doi: 10.1038/s41598-024-66905-1.
The surveillance of drug resistance in the HIV-1 naïve population remains critical to optimizing the effectiveness of antiretroviral therapy (ART), mainly in the era of integrase strand transfer inhibitor (INSTI) regimens. Currently, there is no data regarding resistance to INSTI in Angola since Dolutegravir-DTG was included in the first-line ART regimen. Herein, we investigated the HIV-1 genetic diversity and pretreatment drug resistance (PDR) profile against nucleoside/tide reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), protease inhibitors (PIs), and INSTIs, using a next-generation sequencing (NGS) approach with MinION, established to track and survey DRMs in Angola. This was a cross-sectional study comprising 48 newly HIV-diagnosed patients from Luanda, Angola, screened between March 2022 and May 2023. PR, RT, and IN fragments were sequenced for drug resistance and molecular transmission cluster analysis. A total of 45 out of the 48 plasma samples were successfully sequenced. Of these, 10/45 (22.2%) presented PDR to PIs/NRTIs/NNRTIs. Major mutations for NRTIs (2.2%), NNRTIs (20%), PIs (2.2%), and accessory mutations against INSTIs (13.3%) were detected. No major mutations against INSTIs were detected. M41L (2%) and I85V (2%) mutations were detected for NRTI and PI, respectively. K103N (7%), Y181C (7%), and K101E (7%) mutations were frequently observed in NNRTI. The L74M (9%) accessory mutation was frequently observed in the INSTI class. HIV-1 pure subtypes C (33%), F1 (17%), G (15%), A1 (10%), H (6%), and D (4%), CRF01_AG (4%) were observed, while about 10% were recombinant strains. About 31% of detected HIV-1C sequences were in clusters, suggesting small-scale local transmission chains. No major mutations against integrase inhibitors were detected, supporting the continued use of INSTI in the country. Further studies assessing the HIV-1 epidemiology in the era of INSTI-based ART regimens are needed in Angola.
在整合酶抑制剂（INSTI）方案时代，对 HIV-1 初治人群的耐药性监测仍然至关重要，主要是为了优化抗逆转录病毒治疗（ART）的效果。目前，由于多替拉韦（DTG）已被纳入一线 ART 方案，安哥拉尚未有关于 INSTI 耐药的数据。在此，我们使用 MinION 建立的下一代测序（NGS）方法，调查了 HIV-1 的遗传多样性和针对核苷/核苷酸逆转录酶抑制剂（NRTIs）、非核苷逆转录酶抑制剂（NNRTIs）、蛋白酶抑制剂（PIs）和 INSTIs 的预处理耐药（PDR）谱，该方法用于在安哥拉追踪和监测耐药突变。这是一项横断面研究，共纳入 2022 年 3 月至 2023 年 5 月期间在安哥拉罗安达新诊断的 48 例 HIV 阳性患者。对 PR、RT 和 IN 片段进行了耐药性和分子传播群分析测序。其中，45 份血浆样本中有 45 份成功测序。这些样本中，10/45（22.2%）对 PIs/NRTIs/NNRTIs 有 PDR。检测到 NRTI（2.2%）、NNRTI（20%）、PI（2.2%）和 INSTI（13.3%）的辅助突变的主要耐药突变。未检测到针对 INSTI 的主要耐药突变。分别检测到 NRTI 和 PI 的 M41L（2%）和 I85V（2%）突变。NNRTI 中经常观察到 K103N（7%）、Y181C（7%）和 K101E（7%）突变。INSTI 类中经常观察到 L74M（9%）辅助突变。观察到 HIV-1 纯亚型 C（33%）、F1（17%）、G（15%）、A1（10%）、H（6%）和 D（4%）、CRF01_AG（4%），而约 10%为重组株。约 31%的检测到的 HIV-1C 序列处于聚类中，提示存在小规模的本地传播链。未检测到针对整合酶抑制剂的主要耐药突变，支持在该国继续使用 INSTI。安哥拉需要进一步研究评估 INSTI 为基础的 ART 方案时代的 HIV-1 流行病学。
