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Pretreatment resistance mutations and treatment outcomes in adults living with HIV-1: a cohort study in urban Malawi.
AIDS Research and Therapy ( IF 2.2 ) Pub Date : 2020-05-20 , DOI: 10.1186/s12981-020-00282-3
F Neuhann 1 , A de Forest 1 , E Heger 2 , A Nhlema 3 , C Scheller 4 , R Kaiser 2 , H M Steffen 5 , H Tweya 3 , G Fätkenheuer 6 , S Phiri 3, 7, 8, 9
Affiliation  

BACKGROUND 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. METHODS 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. RESULTS 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. CONCLUSION 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.

中文翻译:

成人HIV-1感染者的治疗前耐药性突变和治疗结果:马拉维市区的一项队列研究。

背景技术在抗逆转录病毒纯真的HIV感染者(PLHIV)中的治疗前耐药性(PDR)代表了治疗失败风险和耐药性HIV变体传播的重要指标。我们评估了马拉维利隆圭的HIV-1感染者中PDR的患病率和治疗效果。方法我们从Lighthouse Tenofovir队列研究(LighTen)中随机选择了200名参与者。在2014年和2015年开始治疗之前抽取血清样本,进行冷冻,然后分析是否存在HIV-1耐药性突变。扩增子通过Stanford HIVdb解释算法8.4进行测序和解释。我们通过在2019年10月的随访期结束时评估临床结局和病毒抑制作用来评估治疗结局。结果在200个样本中的197个中,PDR测试成功。总体NNRTI-PDR患病率为13.7%(27/197)。中级或高级NNRTI-PDR的患病率为11.2%(22/197)。最常见的突变是K103N(5.6%,11/197),其次是Y181C(3.6%,7/197)。在一个案例中,我们检测到NRTI抗性突变(M184V),并与多个NNRTI抗性突变结合。分析的所有HIV-1分离物均为C亚型。在27例NNRTI-PDR患者中,有9例仍活着,接受抗逆转录病毒治疗,并在随访结束时被病毒抑制。结论NNRTI-PDR的流行率高于《全球HIV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前的研究相似,并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,我们的发现强调了在撒哈拉以南非洲地区需要继续进行PDR监测和药物警戒。
更新日期:2020-05-20
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