Molecular epidemiology of a primarily MSM acute HIV‐1 cohort in Bangkok, Thailand and connections within networks of transmission in Asia

Abstract

IntroductionThailand plays a substantial role in global HIV‐1 transmission of CRF01_AE. Worldwide, men who have sex with men (MSM) are at elevated risk for HIV‐1 infection. Hence, understanding HIV‐1 diversity in a primarily Thai MSM cohort with acute infection, and its connections to the broader HIV‐1 transmission network in Asia is crucial for research and development of HIV‐1 vaccines, treatment and cure.MethodsSubtypes and diversity of infecting viruses from individuals sampled from 2009 to 2015 within the RV254/SEARCH 010 cohort were assessed by multiregion hybridization assay (MHAbce), multiregion subtype‐specific PCR assay (MSSPbce) and full‐length single‐genome sequencing (SGS). Phylogenetic analysis was performed by maximum likelihood. Pairwise genetic distances of envelope gp160 sequences obtained from the cohort and from Asia (Los Alamos National Laboratory HIV Database) were calculated to identify potential transmission networks.Results MHAbce/MSSPbce results identified 81.6% CRF01_AE infecting strains in RV254. CRF01_AE/B recombinants and subtype B were found at 7.3% and 2.8% respectively. Western subtype B strains outnumbered Thai B′ strains. Phylogenetic analysis revealed one C, one CRF01_AE/CRF02_AG recombinant and one CRF01_AE/B/C recombinant. Asian network analysis identified one hundred and twenty‐three clusters, including five clusters of RV254 participants. None of the RV254 sequences clustered with non‐RV254 sequences. The largest international cluster involved 15 CRF01_AE strains from China and Vietnam. The remaining clusters were mostly intracountry connections, of which 31.7% included Thai nodes and 43.1% included Chinese nodes.ConclusionWhile the majority of strains in Thailand are CRF01_AE and subtype B, emergence of unique recombinant forms (URFs) are found in a moderate fraction of new HIV‐1 infections. Approaches to vaccine design and immunotherapeutics will need to monitor and consider the expanding proportion of recombinants and the increasing genetic diversity in the region. Identified HIV‐1 transmission networks indicate ongoing spread of HIV‐1 among MSM. As HIV‐1 epidemics continue to expand in other Asian countries, transmission network analyses can inform strategies for prevention, intervention, treatment and cure.

HIV-1 subtype diversity and transmission strain source among men who have sex with men in Guangxi, China

“…The proportion aged 25 years or less was higher than those in studies from Shenzhen, Beijing and Shanghai 26 – 28 , as well as the United States 29 . Our sample was similar to those in Kunming 30 and Thailand 31 .…”

“…We created a table (see Supplementary Table S1 ) to compare the HIV subtype/CRF diversity in western and Asian countries, as well as provinces or large cities in China. The HIV subtype/CRF diversity in Guangxi MSM in the current study was more complicated than that in 2013 11 and those in southeast countries such as Thailand 31 , Malaysia 32 and Singapore 33 . Degrees of diversity were high in Shanghai 28 , Guangdong 26 , Beijing 34 and Sichuan 35 .…”

Dynamics of Human Immunodeficiency Virus-1 Genetic Diversification During Acute Infection

“…Study participants were from the RV254/SEARCH010 cohort (clinicaltrials.gov NCT00796146), a prospective study of participants with AHI in Bangkok, Thailand [ 2 ]. Most were male (96.0%) and men who have sex with men ([MSM] 92.1%) [ 4 ]. The estimated time of HIV exposure was obtained from each participant through self-report.…”

“…Human immunodeficiency virus-1 subtyping was performed using a multiregion hybridization assay (MHAbce) or a multiregion subtype-specific polymerase chain reaction assay (MSS Pbce) as previously described [ 5 , 6 ]. We focused on CRF01_AE infections, the predominant clade in this cohort (81.6%) [ 4 ] that represents the majority of circulating strains in Thailand [ 7 ]. A total of 353 CRF01_AE infections at Fiebig I to IV were identified, among which 98 had sequences retrieved by single genome amplification (SGA) available for genetic analysis.…”

Incorporation of information diffusion model for enhancing analyses in HIV molecular surveillance

“…In such circumstances, a network approach can be more applicable as it does not assume all sequences to be descendants from one common ancestor but rather compares the dissimilarity amongst them [1]. Such genetic network-based analysis is particularly relevant for examining HIV transmission dynamics in the population where multiple subtypes were in circulation [2][3][4]. As a predominantly sexually transmitted infection, HIV forms networks which do not occur randomly but are behaviourally driven and shaped by treatment interventions [5][6].…”