Gemechu Abdella, Mihret Adane, Mengesha Mesfin, Alemayehu Dawit Hailu, Kidane Eleni, Aseffa Abraham, Howe Rawleigh, Seyoum Berhanu, Mulu Andargachew
School of Medical Laboratory Sciences, College of Health and Medical Sciences Haramaya University Harar Ethiopia.
Armauer Hansen Research Institute Addis Ababa Ethiopia.
Health Sci Rep. 2025 Apr 16;8(4):e70672. doi: 10.1002/hsr2.70672. eCollection 2025 Apr.
In Ethiopia, HIV-1 pretreatment drug resistance (PDR) data are limited owing to a lack of routine genotyping resistance tests. This study aimed to determine the prevalence of HIV-1 PDR mutations and genetic diversity among newly diagnosed people with HIV in eastern Ethiopia.
HIV RNA was extracted using Abbott m2000sp. HIV-1 partial pol genes were amplified and sequenced using the Sanger dideoxy method. DRM profiles were examined and interpreted according to the calibrated population resistance (CPR) and Stanford University HIV drug resistance algorithms. A maximum likelihood phylogenetic tree was constructed using PhyML version 3.0 and visualized using the iTOL tool. Bivariable and multivariable logistic regression models were used to identify baseline factors associated with outcomes at a value of < 0.05.
Among newly diagnosed individuals with baseline viral load (≥ 1000 copies/mL) and amplifications were successful, the genotyping success rate was 78.4%. Among the isolates successfully sequenced, three HIV-1 strains were detected, of which 97.1% had HIV-1 subtype C, 1.4% A1C, and 1.4% CF1 recombinant. According to the Stanford HIVDR algorithm, 21.7% of people had at least one drug associated PDR mutation, whereas CPR reported 14.5% DRMs. NNRTIs had the highest PDR mutation rate (13.0%), followed by NRTIs (7.2%) and PIs (2.9%). The most commonly observed major DRMs were: NNRTIs (K103N and G190A), NRTIs (D67G and L210W), and PIs (L90M and I54S). Patients who were bedridden at enrollment were more likely to harbor PDR mutations (AOR: 5.4; 95% CI: 1.53-30.7).
High PDR levels, predominantly for NNRTIs, are observed. During clinical follow-up, special attention should be given to bedridden functional status patients. Further surveillance studies are needed to evaluate the long-term effects of prolonged accumulation of resistance and its transmission on current ART regimens and to design appropriate interventions to halt the HIV epidemic.
在埃塞俄比亚,由于缺乏常规的基因分型耐药性检测,HIV-1治疗前耐药(PDR)数据有限。本研究旨在确定埃塞俄比亚东部新诊断的HIV感染者中HIV-1 PDR突变的流行情况和基因多样性。
使用雅培m2000sp提取HIV RNA。采用桑格双脱氧法对HIV-1部分pol基因进行扩增和测序。根据校准人群耐药性(CPR)和斯坦福大学HIV耐药性算法检查和解释耐药突变(DRM)谱。使用PhyML 3.0版本构建最大似然系统发育树,并使用iTOL工具进行可视化。采用双变量和多变量逻辑回归模型,以<0.05的P值确定与结局相关的基线因素。
在基线病毒载量≥1000拷贝/mL且扩增成功的新诊断个体中,基因分型成功率为78.4%。在成功测序的分离株中,检测到三种HIV-1毒株,其中97.1%为HIV-1 C亚型,1.4%为A1C亚型,1.4%为CF1重组型。根据斯坦福HIVDR算法,21.7%的人至少有一个与药物相关的PDR突变,而CPR报告的DRM为14.5%。非核苷类逆转录酶抑制剂(NNRTIs)的PDR突变率最高(13.0%),其次是核苷类逆转录酶抑制剂(NRTIs,7.2%)和蛋白酶抑制剂(PIs,2.9%)。最常观察到的主要DRM为:NNRTIs(K103N和G190A)、NRTIs(D67G和L210W)和PIs(L90M和I54S)。入组时卧床不起的患者更有可能携带PDR突变(调整优势比:5.4;95%置信区间:1.53-30.7)。
观察到较高的PDR水平,主要针对NNRTIs。在临床随访期间,应特别关注卧床不起的功能状态患者。需要进一步的监测研究,以评估耐药性长期积累及其传播对当前抗逆转录病毒治疗方案的长期影响,并设计适当的干预措施以遏制HIV疫情。