博茨瓦纳 HIV-1 亚型 C 感染的抗逆转录病毒治疗初治和经验丰富成人中与多伟拉韦相关的耐药突变。
Doravirine-associated resistance mutations in antiretroviral therapy naïve and experienced adults with HIV-1 subtype C infection in Botswana.
机构信息
Botswana Harvard AIDS Institute Partnership, Gaborone, Botswana; Department of Medical Sciences, Faculty of Allied Health Professions, University of Botswana, Gaborone, Botswana.
Botswana Harvard AIDS Institute Partnership, Gaborone, Botswana; Department of Biological Sciences, Faculty of Science, University of Botswana, Gaborone, Botswana.
出版信息
J Glob Antimicrob Resist. 2022 Dec;31:128-134. doi: 10.1016/j.jgar.2022.08.008. Epub 2022 Aug 13.
OBJECTIVES
There are limited data on the prevalence of doravirine (DOR)-associated drug resistance mutations in people with HIV (PWH) in Botswana. This cross-sectional, retrospective study aimed to explore the prevalence of DOR-associated resistance mutations among ART-naïve and -experienced PWH in Botswana enrolled in the population-based Botswana Combination Prevention Project (BCPP).
METHODS
A total of 6078 HIV-1C pol sequences were analysed for DOR-associated resistance mutations using the Stanford HIV drug resistance database, and their levels were predicted according to the Stanford DRM penalty scores and resistance interpretation. Virologic failure was defined as HIV-1 RNA load (VL) >400 copies/mL.
RESULTS
Among 6078 PWH, 5999 (99%) had known ART status, and 4529/5999 (79%) were on ART at time of sampling. The suppression rate among ART-experienced was 4517/4729 (96%). The overall prevalence of any DOR-associated resistance mutations was 181/1473 (12.3% [95% confidence interval {CI}: 10.7-14.1]); by ART status: 42/212 (19.8% [95% CI: 14.7-25.4]) among ART-failing individuals (VL ≥400 copies/mL) and 139/1261 (11.0% [95% CI: 9.3-12.9]) among ART-naïve individuals (P < 0.01). Intermediate DOR-associated resistance mutations were observed in 106/1261 (7.8% [95% CI: 6.9-10.1]) in ART-naïve individuals and 29/212 (13.7% [95% CI: 9.4-8.5]) among ART-experienced participants (P < 0.01). High-level DOR-associated resistance mutations were observed in 33/1261 (2.6% [95% CI: 1.8-3.7]) among ART-naïve and 13/212 (6.1% [95% CI: 3.6-10.8]) among ART-failing PWH (P < 0.01). PWH failing ART with at least one EFV/NVP-associated resistance mutation had high prevalence 13/67 (19.4%) of high-level DOR-associated resistance mutations.
CONCLUSION
DOR-associated mutations were rare (11.0%) among ART-naive PWH but present in 62.7% of Botswana individuals who failed NNRTI-based ART with at least one EFV/NVP-associated resistance mutation. Testing for HIV drug resistance should underpin the use of DOR in PWH who have taken first-generation NNRTIs.
目的
博茨瓦纳艾滋病毒感染者（PWH）中多替拉韦（DOR）相关耐药突变的流行率数据有限。这项横断面、回顾性研究旨在探索博茨瓦纳基于人群的博茨瓦纳组合预防项目（BCPP）中接受初治和经治抗逆转录病毒治疗的 PWH 中 DOR 相关耐药突变的流行率。
方法
使用斯坦福 HIV 耐药数据库分析了总共 6078 个 HIV-1C pol 序列，以确定 DOR 相关耐药突变，并根据斯坦福 DRM 罚分和耐药解释预测其水平。病毒学失败定义为 HIV-1 RNA 载量（VL）>400 拷贝/ml。
结果
在 6078 名 PWH 中，5999 名（99%）有已知的 ART 状态，4529/5999 名（79%）在采样时正在接受 ART 治疗。经治者的抑制率为 4517/4729（96%）。任何 DOR 相关耐药突变的总流行率为 181/1473（12.3%[95%置信区间：10.7-14.1]）；按 ART 状态：42/212（19.8%[95%置信区间：14.7-25.4]）在 ART 失败（VL≥400 拷贝/ml）者中，139/1261（11.0%[95%置信区间：9.3-12.9]）在 ART 初治者中（P<0.01）。在 ART 初治者中观察到 106/1261（7.8%[95%置信区间：6.9-10.1]）中等水平 DOR 相关耐药突变，在经治者中观察到 29/212（13.7%[95%置信区间：9.4-8.5]）（P<0.01）。在 ART 初治者中观察到 33/1261（2.6%[95%置信区间：1.8-3.7]）和在 ART 失败者中观察到 13/212（6.1%[95%置信区间：3.6-10.8]）高水平 DOR 相关耐药突变（P<0.01）。至少有 1 种 EFV/NVP 相关耐药突变的 ART 失败的 PWH 中，高水平 DOR 相关耐药突变的流行率很高，为 13/67（19.4%）。
结论
DOR 相关突变在 ART 初治 PWH 中罕见（11.0%），但在至少有 1 种 EFV/NVP 相关耐药突变的博茨瓦纳人群中，接受第一代 NNRTI 治疗失败的个体中存在 62.7%。在曾接受过第一代 NNRTI 治疗的 PWH 中使用 DOR 时，应进行 HIV 耐药性检测。
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