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

Huangbo Yuan,Xuefu Wu,Damien C Tully,Tiejun Zhang,Qiwen Fang,Mingshan Wu,Tingting Shi,Zhenqiu Liu,Xin Zhang

doi:10.1007/s00705-021-05140-9

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.

Highlights

The global scale-up of antiretroviral therapy (ART) for HIV-1 infections has resulted in considerable reductions in HIV/AIDS-related morbidity and mortality [1,2,3]
We identified transmitted-drug resistant HIV among ART-naive HIV-1-infected individuals in China
The overall prevalence of HIV with transmitted drug resistant (TDR) was 4.51%, which is comparable to that reported by Zhao et al and Su et al (3%–5%) [8,9]

Summary

Introduction

The global scale-up of antiretroviral therapy (ART) for HIV-1 infections has resulted in considerable reductions in HIV/AIDS-related morbidity and mortality [1,2,3]. Primary infection with transmitted drug resistant (TDR) HIV strains limits a newly-diagnosed patient’s treatment options and is associated with treatment failure. Previous studies have shown that China had a prevalence of HIV with TDR of approximately 3.6% in ART-naive patients in 2015 [8,9], which was lower than that in Western countries [10,11,12,13]. Given the large number of HIV-infected people and the persistent circulation of HIV in China, the number of patients for whom ART failed because of drug resistance is considerably high in this country

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