Neuhann F, de Forest A, Heger E, Nhlema A, Scheller C, Kaiser R, Steffen H M, Tweya H, Fätkenheuer G, Phiri S
Heidelberg Institute for Global Health, University Hospital of Heidelberg, Im Neuenheimer Feld 130.3, 69120, Heidelberg, Germany.
Institute of Virology, University of Cologne, Faculty of Medicine and University Hospital of Cologne, Cologne, Germany.
AIDS Res Ther. 2020 May 20;17(1):22. doi: 10.1186/s12981-020-00282-3.
Pre-treatment drug resistance (PDR) among antiretroviral drug-naïve people living with HIV (PLHIV) represents an important indicator for the risk of treatment failure and the spread of drug resistant HIV variants. We assessed the prevalence of PDR and treatment outcomes among adults living with HIV-1 in Lilongwe, Malawi.
We selected 200 participants at random from the Lighthouse Tenofovir Cohort Study (LighTen). Serum samples were drawn prior to treatment initiation in 2014 and 2015, frozen, and later analyzed for the presence of HIV-1 drug resistance mutations. Amplicons were sequenced and interpreted by Stanford HIVdb interpretation algorithm 8.4. We assessed treatment outcomes by evaluating clinical outcome and viral suppression at the end of the follow-up period in October 2019.
PDR testing was successful in 197 of 200 samples. The overall NNRTI- PDR prevalence was 13.7% (27/197). The prevalence of intermediate or high level NNRTI- PDR was 11.2% (22/197). The most common mutation was K103N (5.6%, 11/197), followed by Y181C (3.6%, 7/197). In one case, we detected an NRTI resistance mutation (M184V), in combination with multiple NNRTI resistance mutations. All HIV-1 isolates analyzed were of subtype C. Of the 27 patients with NNRTI- PDR, 9 were still alive, on ART, and virally suppressed at the end of follow-up.
The prevalence of NNRTI- PDR was above the critical level of 10% suggested by the Global Action Plan on HIV Drug Resistance. The distribution of drug resistance mutations was similar to that seen in previous studies from the region, and further supports the introduction of integrase inhibitors in first-line treatment in Malawi. Furthermore, our findings underline the need for continued PDR surveillance and pharmacovigilance in Sub-Saharan Africa.
在未接受过抗逆转录病毒治疗的艾滋病毒感染者（PLHIV）中，治疗前耐药性（PDR）是治疗失败风险和耐药艾滋病毒变异传播的重要指标。我们评估了马拉维利隆圭成人艾滋病毒-1感染者中PDR的流行情况和治疗结果。
我们从灯塔替诺福韦队列研究（LighTen）中随机选取了200名参与者。在2014年和2015年开始治疗前采集血清样本，冷冻保存，随后分析是否存在艾滋病毒-1耐药突变。扩增子进行测序，并由斯坦福HIVdb解释算法8.4进行解读。我们通过评估2019年10月随访期结束时的临床结局和病毒抑制情况来评估治疗结果。
200份样本中有197份成功进行了PDR检测。总体非核苷类逆转录酶抑制剂（NNRTI）-PDR患病率为13.7%（27/197）。中高水平NNRTI-PDR患病率为11.2%（22/197）。最常见的突变是K103N（5.6%，11/197），其次是Y181C（3.6%，7/197）。在1例中，我们检测到1例核苷类逆转录酶抑制剂（NRTI）耐药突变（M184V），同时伴有多个NNRTI耐药突变。所有分析的艾滋病毒-1分离株均为C亚型。在27例NNRTI-PDR患者中，9例在随访结束时仍存活，接受抗逆转录病毒治疗（ART）且病毒得到抑制。
NNRTI-PDR患病率高于《全球艾滋病毒耐药性行动计划》建议的10%的临界水平。耐药突变的分布与该地区以往研究相似，进一步支持在马拉维的一线治疗中引入整合酶抑制剂。此外，我们的研究结果强调了撒哈拉以南非洲持续进行PDR监测和药物警戒的必要性。
