Abstract
BackgroundOne major circulating HIV-1 subtype in Southeast Asian countries is CRF01_AE, but little is known about its epidemiology in Japan. We conducted a molecular phylodynamic study of patients newly diagnosed with CRF01_AE from 2003 to 2010.MethodsPlasma samples from patients registered in Japanese Drug Resistance HIV-1 Surveillance Network were analyzed for protease-reverse transcriptase sequences; all sequences undergo subtyping and phylogenetic analysis using distance-matrix-based, maximum likelihood and Bayesian coalescent Markov Chain Monte Carlo (MCMC) phylogenetic inferences. Transmission clusters were identified using interior branch test and depth-first searches for sub-tree partitions. Times of most recent common ancestor (tMRCAs) of significant clusters were estimated using Bayesian MCMC analysis.ResultsAmong 3618 patient registered in our network, 243 were infected with CRF01_AE. The majority of individuals with CRF01_AE were Japanese, predominantly male, and reported heterosexual contact as their risk factor. We found 5 large clusters with ≥5 members and 25 small clusters consisting of pairs of individuals with highly related CRF01_AE strains. The earliest cluster showed a tMRCA of 1996, and consisted of individuals with their known risk as heterosexual contacts. The other four large clusters showed later tMRCAs between 2000 and 2002 with members including intravenous drug users (IVDU) and non-Japanese, but not men who have sex with men (MSM). In contrast, small clusters included a high frequency of individuals reporting MSM risk factors. Phylogenetic analysis also showed that some individuals infected with HIV strains spread in East and South-eastern Asian countries.ConclusionsIntroduction of CRF01_AE viruses into Japan is estimated to have occurred in the 1990s. CFR01_AE spread via heterosexual behavior, then among persons connected with non-Japanese, IVDU, and MSM. Phylogenetic analysis demonstrated that some viral variants are largely restricted to Japan, while others have a broad geographic distribution.
Highlights
Since the first HIV-1-infected case was identified in Japan in 1985, the cumulative number of reported cases of HIV/AIDS has been increasing every year, reaching 18,447 by the end of 2010 [1]
Subtype B tends to be found in men who have sex with men (MSM) and Japanese people
We report our results from applying the phylodynamics approach to these sequence data to understand trends in the CRF01_AE outbreak in Japan, genetic relationships between the circulating strains within Japan and strains observed in the surrounding Asian countries, details of their transmission risk factors, and to identify the target populations for effective action plans to prevent further transmission of CRF01_AE
Summary
Since the first HIV-1-infected case was identified in Japan in 1985, the cumulative number of reported cases of HIV/AIDS has been increasing every year, reaching 18,447 by the end of 2010 [1]. The major HIV-1 subtype in the 1980s in Japan was subtype B [2] followed by CRF01_AE [3]. Overall the CRF01_AE is substantial, accounting for an estimated 36% of HIV in South, Southeast, and East Asia (Los Alamos database) in CRF01_AE was likely introduced into Japan’s heterosexual population in the early phase of the epidemic [3,4,7], but the characteristics of the spread of CRF01_AE in Japan have not been extensively investigated. CRF01_AE cases are significantly linked to heterosexual transmission [3,16,17] and non-Japanese people [16]. One major circulating HIV-1 subtype in Southeast Asian countries is CRF01_AE, but little is known about its epidemiology in Japan. We conducted a molecular phylodynamic study of patients newly diagnosed with CRF01_AE from 2003 to 2010
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