HIV-1 Drug Resistance and Genetic Transmission Networks Among MSM Failing Antiretroviral Therapy in South China 2014-2019

Abstract

Background: Guangdong, located in South China, is one of the areas heavily affected by HIV-1 in China. The transmission of HIV-1 among men who have sex with men (MSM) has gradually been increasing in Guangdong.

Objective: To investigate the characteristics of the HIV-1 drug resistance, and genetic transmission networks in MSM with antiretroviral therapy (ART) failure from 2014 to 2019 in Guangdong.

Methods: HIV-1 pol gene sequences were amplified. An online subtyping tool was used to determine the genotype, and a maximum likelihood phylogenetic tree was reconstructed to confirm the genotype results. The Stanford University HIV Drug Resistance Database was used to analyse the sequences of drug resistance mutations (DRMs) and drug resistance profiles. A pairwise Tamura-Nei 93 genetic distance-based method was used to analyse the genetic transmission networks.

Results: Of 393 sequences isolated from HIV-infected MSM with ART failure, CRF01_AE (47.3%), CRF07_BC (21.4%) and CRF55_01B (21.4%) were the top three strains. 55.2% individuals harboured NRTI DRMs, whereas 67.4% carried NNRTI DRMs. 96.8% cases harboured mutations resistance to NRTIs or NNRTIs at high-level. The most common DRMs were M184I/V (42.2%), followed by V179D/E (37.9%) and K65R (27.2%). Of the subtype B sequences, no sequence fell into a cluster. Of the CRF01_AE, CRF55_01B, and CRF59_01B sequences, 14.5%, 61.9%, and 33.3% fell into clusters, respectively. Of the CRF07_BC sequences, 39.3% fell into clusters. The majority of MSM in transmission networks were concentrated at age below 35 years old, with multiple links. Moreover, approximately 54.8% of MSM had more than 2 potential transmission partners.

Conclusion: Drug resistance mutations more frequently occurred in NNRTIs among MSM with ART failure in Guangdong Province. Transmission network analysis revealed a complex transmission pattern, and more attention should be given to younger HIV-1-infected MSM with multiple links.

Keywords: HIV-1; MSM; drug resistance; genetic transmission networks.

Figure 1

Distribution characteristics of HIV-1 genotypes among MSM with ART failure in Guangdong Province from 2014 to 2019. The maximum likelihood phylogenetic tree was constructed using PhyML 3.0. The reference sequences, including nine subtypes (A–D, F–H, J and K), CRF01_AE, CRF07_BC, CRF08_BC, CRF55_01B, and CRF59_01B, were downloaded from the Los Alamos HIV Sequence Database (https://www.hiv.lanl.gov/content/index). Different colour lines represent different genotypes. The subtype H sequences were selected as the outgroup. aLTR values higher than 0.9 were used to identify lineages and are indicated at the corresponding nodes of the tree.

Figure 2

Age- and drug-resistance-associated genetic transmission networks of different genotype sequences. The networks were constructed using Cytoscape with a pairwise genetic distance analysed by using HyPhy software. A total of 27 CRF01_AE sequences (A), 33 CRF07_BC sequences (B), 52 CRF55_01B sequences (C), and 3 CRF59_01B sequences (D) were used for genetic transmission network analysis, and the largest cluster had 48 sequences. Different colours and shapes represent sequences from different age groups or those showing drug resistance or not, respectively.