Department of Medical Laboratory Science, College of Medicine and Health Science, Debre Tabor University, Debre Tabor, Ethiopia.
Armauer Hansen Research Institute, Addis Ababa, Ethiopia.
Retrovirology. 2020 Sep 29;17(1):33. doi: 10.1186/s12977-020-00542-0.
The development of pretreatment drug resistance (PDR) is becoming an obstacle to the success of antiretroviral therapy (ART). Besides, data from developing settings including Ethiopia is still limited. Therefore, this study was aimed to assess HIV-1 genetic diversity and PDR mutations among ART-naive recently diagnosed HIV-1 infected individuals in Addis Ababa, Ethiopia.
Institutional based cross-sectional study was conducted from June to December 2018 in Addis Ababa among ART-naive recently diagnosed individuals. Partial HIV-1 pol region covering the entire protease (PR) and partial reverse transcriptase (RT) regions of 51 samples were amplified and sequenced using an in-house assay. Drug resistance mutations were examined using calibrated population resistance (CPR) tool version 6.0 from the Stanford HIV drug resistance database and the International Antiviral Society-USA (IAS-USA) 2019 mutation list.
According to both algorithms used, 9.8% (5/51) of analyzed samples had at least one PDR Mutation. PDR mutations to Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs) were the most frequently detected (7.8% and 9.8%, according to the CPR tool and IAS-USA algorithm, respectively). The most frequently observed NNRTIs-associated mutations common to both algorithms were K103N (2%), Y188L (2%), K101E (2%), and V106A (2%), while E138A (2%) was observed according to IAS-USA only. Y115F and M184V (mutations that confer resistance to NRTIs) dual mutations were detected according to both criteria in a single study participant (2%). PDR mutation to protease inhibitors was found to be low (only G73S; 2% according to the CPR tool). Phylogenetic analysis showed that 98% (50/51) of the study participants were infected with HIV-1C virus while one individual (2%) was infected with HIV-1A1 virus.
This study showed an increased level of PDR and persistence HIV-1C clade homogeneity after 15 years of the rollout of ART and 3 decades of HIV-1C circulation in Ethiopia, respectively. Therefore, we recommend routine baseline genotypic drug resistance testing for all newly diagnosed HIV infected patients before initiating treatment. This will aid the selection of appropriate therapy in achieving the 90% of patients having an undetectable viral load in consonance with the UN target.
预处理耐药(PDR)的发展正成为抗逆转录病毒治疗(ART)成功的障碍。此外,包括埃塞俄比亚在内的发展中地区的数据仍然有限。因此,本研究旨在评估埃塞俄比亚亚的斯亚贝巴新诊断的 HIV-1 感染未经治疗的个体中 HIV-1 遗传多样性和 PDR 突变。
2018 年 6 月至 12 月,在亚的斯亚贝巴进行了一项基于机构的横断面研究,对象为新诊断未经治疗的 HIV-1 感染者。使用内部检测法扩增并测序了 51 个样本的 HIV-1 pol 区的部分区域,包括整个蛋白酶(PR)和部分逆转录酶(RT)区。使用斯坦福 HIV 耐药数据库校准人群耐药(CPR)工具版本 6.0 和国际抗病毒学会-美国(IAS-USA)2019 突变列表检查耐药突变。
根据使用的两种算法,分析的 51 个样本中,有 9.8%(5/51)至少有一种 PDR 突变。非核苷类逆转录酶抑制剂(NNRTI)耐药突变最为常见(根据 CPR 工具和 IAS-USA 算法,分别为 7.8%和 9.8%)。两种算法均观察到最常见的 NNRTI 相关突变是 K103N(2%)、Y188L(2%)、K101E(2%)和 V106A(2%),而仅 IAS-USA 观察到 E138A(2%)。根据两种标准,均在单个研究参与者中检测到 Y115F 和 M184V(对 NRTIs 耐药的突变)双重突变(2%)。蛋白酶抑制剂耐药突变发现很低(仅 G73S;根据 CPR 工具为 2%)。系统进化分析显示,98%(50/51)的研究参与者感染了 HIV-1C 病毒,而 1 名参与者(2%)感染了 HIV-1A1 病毒。
本研究表明,在 ART 推出 15 年后和 HIV-1C 循环 30 年后,埃塞俄比亚的 PDR 水平增加,HIV-1C 分支的同质性保持不变。因此,我们建议对所有新诊断的 HIV 感染患者在开始治疗前进行常规的基线基因型耐药性检测。这将有助于选择适当的治疗方法,实现 90%的患者病毒载量不可检测,符合联合国的目标。