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坦桑尼亚达累斯萨拉姆地区在使用替诺福韦和常规病毒载量监测时代的治疗前和获得性 HIV 耐药情况。

Pre-treatment and acquired HIV drug resistance in Dar es Salaam, Tanzania in the era of tenofovir and routine viral load monitoring.

机构信息

Joint Research Center for Human Retrovirus Infection, Kumamoto University, Kumamoto, Japan.

International Research Center for Medical Sciences, Kumamoto University, Kumamoto, Japan.

出版信息

J Antimicrob Chemother. 2019 Oct 1;74(10):3016-3020. doi: 10.1093/jac/dkz272.

Abstract

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 (>400 copies/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.

摘要

目的

在坦桑尼亚实施“治必治”策略、病毒学监测和逐步增加使用替诺福韦的情况下,我们研究了治疗前和获得性 HIV 耐药突变(DRMs)的流行情况和模式。

方法

2017 年 6 月至 10 月期间,从坦桑尼亚达累斯萨拉姆穆希比利国家医院护理和治疗诊所接受治疗但病毒载量仍高于 400 拷贝/ml 的 166 名和未经治疗的初治(ART-naive)的 60 名 HIV-1 感染成人的血浆中分离病毒 RNA。通过 PCR 扩增病毒基因编码的蛋白酶和逆转录酶,并直接测序。

结果

对成功扩增样本进行病毒基因分型,发现 14/47(29.8%)初治的无耐药组中存在治疗前耐药突变。其中,7/47(14.9%)存在至少一种对默认一线方案中的一种药物具有高度耐药性的突变。在治疗但病毒载量仍高的患者中,在 100/111(90%)患者中发现耐药突变,其中发现针对 NNRTI、NRTI 和 PI 的耐药突变分别为 95/100(95%)、92/100(92%)和 13/100(13%)。在失败时使用含替诺福韦方案的 18/36(50%)患者中发现了替诺福韦耐药突变 K65R 和 K70G/E 或包括 M41L 和 L210W 在内的≥3 种胸苷类似物耐药突变。有 4 名患者携带多种耐药突变,这可能使所有可用的抗逆转录病毒治疗方案在坦桑尼亚失去疗效。

结论

总之,治疗前和获得性耐药突变的发生率很高,这对坦桑尼亚的 ART 方案的疗效构成了重大风险。需要提供新一代具有更高耐药遗传屏障的抗逆转录病毒药物和强有力的治疗监测,以实现有效和可持续的 HIV 治疗。

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