Trends in Pretreatment HIV-1 Drug Resistance in Antiretroviral Therapy-naive Adults in South Africa, 2000-2016: A Pooled Sequence Analysis
Trends in Pretreatment HIV-1 Drug Resistance in Antiretroviral Therapy-naive Adults in South Africa, 2000-2016: A Pooled Sequence Analysis
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DOI：
10.1016/j.eclinm.2019.03.006
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发表时间：
2019-03-01
影响因子：
15.1
通讯作者：
de Oliveira, Tulio
中科院分区：
文献类型：
--
作者：
Chimukangara, Benjamin;Lessells, Richard J.;de Oliveira, Tulio
背景：南非拥有世界上最大的公共抗逆转录病毒疗法（ART）项目。我们评估了南非未接受过抗逆转录病毒治疗的成年人中治疗前HIV - 1耐药性（PDR）的时间趋势。
方法：我们纳入了2000年至2016年间进行的研究数据集，这些数据集包含来自十多名未接受过抗逆转录病毒治疗的成年人的HIV - 1 pol基因序列。我们分析了这些序列中101种耐药突变的存在情况。我们按采样年份对序列进行汇总，并使用广义线性混合模型进行序列水平分析，将数据集作为随机效应纳入其中。
结果：我们确定了38个数据集，并检索到6880个HIV - 1 pol基因序列用于分析。直到2009年，PDR的年度汇总患病率一直保持在5%以下，然后在2015年上升至11.9%的峰值（95%置信区间（CI）为9.2 - 15.0）。非核苷类逆转录酶抑制剂（NNRTI）PDR的年度汇总患病率直到2011年一直保持在5%以下，然后到2014年上升至10.0%（95% CI为8.4 - 11.8）。在2000年至2016年间，NNRTI PDR每年增加1.18倍（95% CI为1.13 - 1.23）（p < 0.001），核苷类逆转录酶抑制剂PDR每年增加1.10倍（95% CI为1.05 - 1.16）（p = 0.001）。
解释：南非PDR的增加对结束艾滋病流行的努力构成了威胁。这些发现支持了最近修改标准一线抗逆转录病毒治疗方案的决定，但也强调了需要采取更广泛的公共卫生行动来防止耐药性HIV的进一步出现和传播。
资金来源：本研究项目由南非医学研究委员会（MRC）资助，资金来自国家财政部的经济竞争力和支持计划。
免责声明：本出版物的内容仅由作者负责，不一定代表美国疾病控制与预防中心（CDC）的官方观点。（C）2019年由爱思唯尔有限公司出版。这是一篇在CC BY - NC - ND许可下的开放获取文章
Background: South Africa has the largest public antiretroviral therapy (ART) programme in the world. We assessed temporal trends in pretreatment HIV-1 drug resistance (PDR) in ART-naive adults from South Africa.Methods: We included datasets from studies conducted between 2000 and 2016, with HIV-1 pol sequences from more than ten ART-naive adults. We analysed sequences for the presence of 101 drug resistance mutations. We pooled sequences by sampling year and performed a sequence-level analysis using a generalized linear mixed model, including the dataset as a random effect.Findings: We identified 38 datasets, and retrieved 6880 HIV-1 pol sequences for analysis. The pooled annual prevalence of PDR remained below 5% until 2009, then increased to a peak of 11.9% (95% confidence interval (CI) 9.2-15.0) in 2015. The pooled annual prevalence of non-nucleoside reverse-transcriptase inhibitor (NNRTI) PDR remained below 5% until 2011, then increased to 10.0% (95% CI 8.4-11.8) by 2014. Between 2000 and 2016, there was a 1.18-fold (95% CI 1.13-1.23) annual increase in NNRTI PDR (p < 0.001), and a 1.10-fold (95% CI 1.05-1.16) annual increase in nucleoside reverse-transcriptase inhibitor PDR (p = 0.001). Interpretation: Increasing PDR in South Africa presents a threat to the efforts to end the HIV/AIDS epidemic. These findings support the recent decision to modify the standard first-line ART regimen, but also highlights the need for broader public health action to prevent the further emergence and transmission of drug-resistant HIV.Source of Funding: This research project was funded by the South African Medical Research Council (MRC) with funds from National Treasury under its Economic Competitiveness and Support Package.Disclaimer: The contents of this publication are solely the responsibility of the authors and do not necessarily represent the official views of CDC. (C) 2019 Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license