艾滋病毒-1初治人群的耐药性监测对于优化抗逆转录病毒疗法(ART)的有效性仍然至关重要。主要在整合酶链转移抑制剂(INSTI)方案的时代。目前,由于Dolutegravir-DTG被纳入ART一线方案,安哥拉没有关于INSTI耐药的数据.在这里,我们调查了HIV-1的遗传多样性和抗核苷/肽逆转录酶抑制剂(NRTIs)的预处理药物抗性(PDR)谱,非核苷逆转录酶抑制剂(NNRTIs),蛋白酶抑制剂(PIs),和INSTIs,使用MinION的下一代测序(NGS)方法,建立跟踪和调查安哥拉的DRM。这是一项横断面研究,包括来自罗安达的48名新诊断为HIV的患者,安哥拉,在2022年3月至2023年5月期间放映。PR,RT,和IN片段测序进行耐药性和分子传递聚类分析。48个血浆样品中的总共45个被成功地测序。其中,10/45(22.2%)将PDR提交给PI/NRTIs/NNRTIs。NRTIs的主要突变(2.2%),NNRTI(20%),PI(2.2%),并检测到针对INSTIs的辅助突变(13.3%)。未检测到针对INSTIs的主要突变。M41L(2%)和I85V(2%)突变检测为NRTI和PI,分别。K103N(7%),Y181C(7%),在NNRTI中经常观察到K101E(7%)突变。在INSTI类中经常观察到L74M(9%)辅助突变。HIV-1纯亚型C(33%),F1(17%),G(15%),A1(10%),H(6%),和D(4%),观察到CRF01_AG(4%),而约10%为重组菌株。检测到的HIV-1C序列中约有31%成簇,建议小规模的局部传播链。未检测到针对整合酶抑制剂的主要突变,支持在该国继续使用INSTI。安哥拉需要进一步研究评估基于INSTI的ART方案时代的HIV-1流行病学。
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.