Pre-treatment and acquired HIV drug resistance in Dar es Salaam, Tanzania in the era of tenofovir and routine viral load monitoring
Pre-treatment and acquired HIV drug resistance in Dar es Salaam, Tanzania in the era of tenofovir and routine viral load monitoring
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DOI：
10.1093/jac/dkz272
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发表时间：
2019-10-01
影响因子：
5.2
通讯作者：
Ueno, Takamasa
中科院分区：
文献类型：
--
作者：
Barabona, Godfrey;Mahiti, Macdonald;Ueno, Takamasa
我们调查了坦桑尼亚治疗前和获得性艾滋病毒耐药突变（DRMs）的流行情况和模式，作为“治疗所有”战略、病毒学监测和逐步增加替诺福韦的使用正在艾滋病毒治疗规划中实施。方法从2017年6月至10月在坦桑尼亚达累斯萨拉姆Muhimbili国家医院的护理和治疗诊所就诊的60名未接受art治疗和166名治疗但病毒感染的成人（100 400拷贝/mL）血浆中分离病毒RNA。用PCR扩增病毒蛋白酶和逆转录酶基因，并直接测序。结果成功扩增样本的病毒基因分型显示，14/47（29.8%）未接受art治疗的受试者中存在治疗前DRMs。其中，7/47（14.9%）携带突变，对至少一种默认一线治疗方案的药物具有高度耐药性。在治疗但病毒感染的受试者中，DRMs的检出率为100/111(90%)，其中NNRTI、NRTI和PI的检出率分别为95/100（95%）、92/100（92%）和13/100（13%）。替诺福韦耐药突变K65R和K70G/E或>= 3胸苷类似物耐药突变，包括M41L和L210W，在18/36（50%）含替诺福韦治疗失败的受试者中发现。4名患者携带多种drm，这可能导致对坦桑尼亚所有可用的抗逆转录病毒治疗方案产生耐药性。综上所述，治疗前和获得性drm非常普遍，这对坦桑尼亚抗逆转录病毒治疗方案的有效性构成了重大风险。为了有效和可持续地治疗艾滋病毒，有必要提供具有更高耐药遗传屏障和强有力的治疗监测的新一代抗逆转录病毒药物。
Objectives We investigated the prevalence and patterns of pre-treatment and acquired HIV drug resistance mutations (DRMs) in Tanzania as a 'treat all' strategy, virological monitoring and the progressive increase in usage of tenofovir are being implemented in HIV treatment programmes.Methods Viral RNA was isolated from plasma of 60 ART-naive and 166 treated-but-viraemic (>400copies/mL) HIV-1-infected adults attending a care and treatment clinic at Muhimbili National Hospital, Dar es Salaam, Tanzania, between June and October 2017. Viral genes encoding protease and reverse transcriptase were amplified by PCR and directly sequenced.Results Viral genotyping of successfully amplified samples revealed pre-treatment DRMs in 14/47 (29.8%) ART-naive subjects. Of these, 7/47 (14.9%) harboured mutations that confer high-level resistance to at least one drug of the default first-line regimen. In treated-but-viraemic subjects, DRMs were found in 100/111 (90%), where DRMs against NNRTI, NRTI and PI were observed in 95/100 (95%), 92/100 (92%) and 13/100 (13%), respectively. Tenofovir-resistance mutations K65R and K70G/E or >= 3 thymidine analogue resistance mutations including M41L and L210W were found in 18/36 (50%) subjects on a tenofovir-containing regimen at failure. Four patients harboured multiple DRMs, which can confer resistance to all available ART regimens in Tanzania.Conclusions Taken together, pre-treatment and acquired DRMs were highly prevalent, which represents a major risk for the efficacy of ART programmes in Tanzania. Availability of a newer generation of antiretroviral drugs with a higher genetic barrier to resistance and robust treatment monitoring is warranted for effective and sustainable HIV treatment.