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Prevalence of transmitted HIV-1 drug resistance among treatment-naive individuals in China, 2000-2016

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Abstract

Human immunodeficiency virus (HIV) with transmitted drug-resistance (TDR) limits the therapeutic options available for treatment-naive HIV patients. This study aimed to further our understanding of the prevalence and transmission characteristics of HIV with TDR for the application of first-line antiretroviral regimens. A total of 6578 HIV-1 protease/reverse-transcriptase sequences from treatment-naive individuals in China between 2000 and 2016 were obtained from the Los Alamos HIV Sequence Database and were analyzed for TDR. Transmission networks were constructed to determine genetic relationships. The spreading routes of large TDR clusters were identified using a Bayesian phylogeographic framework. TDR mutations were detected in 274 (4.51%) individuals, with 1.40% associated with resistance to nucleoside reverse transcriptase inhibitors, 1.52% to non-nucleoside reverse transcriptase inhibitors, and 1.87% to protease inhibitors. The most frequent mutation was M46L (58, 0.89%), followed by K103N (36, 0.55%), M46I (36, 0.55%), and M184V (26, 0.40%). The prevalence of total TDR initially decreased between 2000 and 2010 (OR = 0.83, 95% CI 0.73–0.95) and then increased thereafter (OR = 1.50, 95% CI 1.13–1.97). The proportion of sequences in a cluster (clustering rate) among HIV isolates with TDR sequences was lower than that of sequences without TDR (40.5% vs. 48.8%, P = 0.023) and increased from 27.3% in 2005–2006 to 63.6% in 2015–2016 (P < 0.001). While most TDR mutations were associated with reduced relative transmission fitness, mutation M46I was associated with higher relative transmission fitness than the wild-type strain. This study identified a low-level prevalence of TDR HIV in China during the last two decades. However, the increasing TDR HIV rate since 2010, the persistent circulation of drug resistance mutations, and the expansion of self-sustaining drug resistance reservoirs may compromise the efficacy of antiretroviral therapy programs.

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Funding

This study was supported by the Natural Science Foundation of China (81772170) and by the National Key Research and Development Program of China (No. 2017YFC0211704).

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Authors and Affiliations

  1. Department of Epidemiology, School of Public Health, Fudan University, Shanghai, 200237, China

    Huangbo Yuan, Xuefu Wu, Mingshan Wu, Qiwen Fang, Xin Zhang, Tingting Shi & Tiejun Zhang

  2. State Key Laboratory of Genetic Engineering, Human Phenome Institute, and School of Life Sciences, Fudan University, Shanghai, China

    Huangbo Yuan & Zhenqiu Liu

  3. Department of Infectious Disease Epidemiology, London School of Hygiene & Tropical Medicine, London, UK

    Damien C. Tully

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  1. Huangbo Yuan
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Correspondence to Tiejun Zhang.

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Yuan, H., Liu, Z., Wu, X. et al. Prevalence of transmitted HIV-1 drug resistance among treatment-naive individuals in China, 2000-2016. Arch Virol 166, 2451–2460 (2021). https://doi.org/10.1007/s00705-021-05140-9

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