Phylodynamic Profile of HIV-1 Subtype B, CRF01_AE and the Recently Emerging CRF51_01B among Men Who Have Sex with Men (MSM) in Singapore

Kim Tien Ng,Yee Sin Leo,Kok Keng Tee,Kuan Kiat Chew,Mei Ting Tan,Adeeba Kamarulzaman,Oliver Laeyendecker,Oon Tek Ng,Thomas C Quinn,Wei Xin Khong,Kah Ying Ng,Palvinder Kaur Singh,Joe Kwan Yap,Marco Salemi

doi:10.1371/journal.pone.0080884

Abstract

HIV-1 subtype B and CRF01_AE are the predominant infecting subtypes among men who have sex with men (MSM) in Singapore. The genetic history, population dynamics and pattern of transmission networks of these genotypes remain largely unknown. We delineated the phylodynamic profiles of HIV-1 subtype B, CRF01_AE and the recently characterized CRF51_01B strains circulating among the MSM population in Singapore. A total of 105 (49.5%) newly-diagnosed treatment-naïve MSM were recruited between February 2008 and August 2009. Phylogenetic reconstructions of the protease gene (HXB2: 2239 – 2629), gp120 (HXB2: 6942 – 7577) and gp41 (HXB2: 7803 – 8276) of the env gene uncovered five monophyletic transmission networks (two each within subtype B and CRF01_AE and one within CRF51_01B lineages) of different sizes (involving 3 – 23 MSM subjects, supported by posterior probability measure of 1.0). Bayesian coalescent analysis estimated that the emergence and dissemination of multiple sub-epidemic networks occurred between 1995 and 2005, driven largely by subtype B and later followed by CRF01_AE. Exponential increase in effective population size for both subtype B and CRF01_AE occurred between 2002 to 2007 and 2005 to 2007, respectively. Genealogical estimates suggested that the novel CRF51_01B lineages were probably generated through series of recombination events involving CRF01_AE and multiple subtype B ancestors. Our study provides the first insight on the phylodynamic profiles of HIV-1 subtype B, CRF01_AE and CRF51_01B viral strains circulating among MSM in Singapore.

Highlights

Human immunodeficiency virus type 1 (HIV-1)is known for its extreme genetic diversity, owing to its high mutation rates, high viral turnovers and the persistent nature of its infection [1]
HIV-1 transmission is increasing among the men who have sex with men (MSM) population in Singapore and other countries in the region, a comprehensive analysis on the viral diversity, growth and temporal dynamics in this high-risk group remains scarce in Southeast Asia
Bayesian coalescent analysis estimated that the time of most recent common ancestor (tMRCA) for all transmission networks originated between 1995 and 2005, with subtype B radiated around late 1990s, followed closely by CRF01_AE that emerged in early 2000s

Summary

Introduction

Human immunodeficiency virus type 1 (HIV-1)is known for its extreme genetic diversity, owing to its high mutation rates, high viral turnovers and the persistent nature of its infection [1]. Recent surveillance reports have shown significant increase in the prevalence of HIV-1 infections among MSM in several Asian countries [4,5,6]. A more recent study further confirmed that HIV-1 subtype B and CRF01_AE continue to be the predominant genotypes circulating in Singapore, with a higher CRF01_AE prevalence among MSM [8]. Despite the significant clinical and epidemiological impact attributed to HIV-1 subtype B, CRF01_AE and CRF51_01B in Singapore [10], the genetic history, population dynamics and pattern of transmission networks of these genotypes remains largely unexplored. In the present study, based on the HIV-1 protease and env (gp120 and gp41) genes, we attempt to delineate the genetic history and the phylodynamic profiles of HIV-1 subtype B and CRF01_AE, as well as the little known CRF51_01B lineages isolated from the MSM population in Singapore, by using a suite of phylogenetic tools that involve maximum likelihood and Bayesian coalescence approaches

Methods

Results

Conclusion