Prevalence of Drug Resistance and Genetic Transmission Networks Among Human Immunodeficiency Virus/Acquired Immunodeficiency Syndrome Patients with Antiretroviral Therapy Failure in Guangxi, China.

Prevalence of drug resistance (DR) challenges the epidemic control of human immunodeficiency virus (HIV)-1. However, little is known about DR among patients with antiretroviral therapy (ART) failure in Guangxi province, China. This cross-sectional study was aimed to investigate the prevalence of DR and the characteristics of DR sequences in the genetic transmission network among HIV-1 patients with ART failure in Guangxi. We enrolled 358 eligible patients between 2012 and 2018. Blood samples were subjected to reverse transcription polymerase chain reaction, followed by sequencing of the HIV-1 polymerase (pol) gene. An online subtyping tool and neighbor-joining phylogenetic tree were used to determine the genotype. HIV-TRACE tool was used to constructed transmission network with a pairwise genetic distance of 0.013. DR was analyzed using the Stanford University HIV Drug Resistance Database. We obtained 293 pol-sequences from participants; CRF01_AE (75.4%), CRF 08_BC (15.7%), and CRF07_BC (8.5%) were the main subtypes, and an A1 subtype was detected in Guangxi for the first time. The overall prevalence of DR was 32.4% (95/293). Among those with identified DR, 25.6% were against non-nucleoside analog reverse-transcriptase inhibitors (NNRTIs), 17.7% were against nucleoside analog reverse-transcriptase inhibitors (NRTIs), and 14.3% were against both NRTIs and NNRTIs. The common drug-resistant mutations were M184V (10.2%), K103N (10.6%) and V179D (6.1%). The patients located in the southern Guangxi [adjust odds ratio (AOR) = 10.87], or whose blood plasma were taken in 2017-2018 (AOR = 3.98) had an increased risk of DR. Of the CRF01_AE, CRF07_BC, and CRF08_BC sequences, 18.6%, 8.0%, and 13.0% fell into clusters, respectively. Nine (9.7%) sequences from patients with DR fell into three clusters. The largest cluster containing 11 individuals was the CRF01_AE subtype, 27.3% of whom were DR patients. Although the prevalence of DR among ART failure patients in Guangxi was at a low level, the continuous surveillance of DR in ART patients is necessary.

Using Molecular Transmission Networks to Reveal the Epidemic of Pretreatment HIV-1 Drug Resistance in Guangxi, China.

INTRODUCTION: Pretreatment drug resistance (PDR) is becoming an obstacle to the success of ART. This study investigated the prevalence of PDR and the transmission clusters (TCs) of drug resistance mutations (DRMs) in two cities where drug abuse used to be high to describe the local HIV-1 transmission dynamics. METHODS: Plasma samples were obtained from 1,027 ART-naïve patients in Guangxi. Viral subtypes and DRMs were identified. Transmission network and related factors were also determined. RESULTS: A total of 1,025 eligible sequences were obtained from Qinzhou (65.8%) and Baise (34.2%) cities. The predominant HIV-1 genotype was CRF08_BC (45.0%), followed by CRF01_AE (40.9%). The overall prevalence of PDR was 8.3%, and resistance to NNRTI was the most common. Putative links with at least one other sequence were found in 543/1,025 (53.0%) sequences, forming 111 clusters (2-143 individuals). The most prevalent shared DRMs included V106I (45.35%), V179D (15.1%), and V179E (15.1%). Clusters related to shared DRMs were more frequent and larger in CRF08_BC. The prevalence of shared DRMs increased with time, while the proportion of PDR gradually decreased. Age > 50 years was associated with clustering. Subtype CRF08_BC was more likely to have DRMs, PDR propagation, and DRM sharing. CONCLUSION: PDR prevalence is moderate in this region. The association between PDR and subtype CRF08_BC suggested that DRMs spreading from injection drug users (IDUs) to heterosexuals (HETs) might be the major source of PDR in this region. Our findings highlight the significance of continuous surveillance of PDR.

Genomic Characterization of a Novel HIV Type 1 Strain Originating from CRF07_BC and CRF01_AE by Heterosexual Transmission in the Lingshan Prefecture of Guangxi Province, China.

Recently, an increasing number of circulating recombinant forms (CRFs) and unique recombinant forms of HIV-1 have been identified in China, contributing substantially to the genetic variability of this virus. This study reports a novel second-generation recombinant form of HIV-1 (GX2015QZLS204), composed of segments from the CRF07_BC and CRF01_AE strains, which was isolated from an HIV-positive male individual infected through heterosexual contact, while residing in the Guangxi province of southwest China. Analysis of the near full-length genome sequence showed that one segment of the CRF01_AE virus subtype was inserted into the CRF07_BC subtype backbone. Recombination analysis demonstrated that the genome of GX2015QZLS204 was separated into seven segments with six breakpoints. Subregion trees constructed by the neighbor-joining method confirmed that the CRF01_AE segment was from the previously identified CRF01_AE cluster 2, and the CRF07_BC segment correlated with the CRF07_BC strain originating from the Jiangxi and Xinjiang provinces of China. The emergence of GX2015QZLS204 highlights the frequent generation of novel recombinant forms and the increasing complications of the HIV-1 epidemic among heterosexual transmission (HET) groups in China. This highlights the importance of monitoring HIV-1 molecular epidemiological characteristics and the urgent need for reduction of the HIV-1 epidemic among HET groups in China.