HIV-1 Transmission Networks Among Men Who Have Sex With Men in Asia TO THE EDITOR—We read with great interest the recent article by Yang et al [1], which reports the high incidence of human immunodeficiency virus type 1 (HIV-1) infection and syphilis among men who have sex with men (MSM) in Jiangsu and Changzhou cities in China. The potential role of transmission networks in fueling the AIDS epidemic among MSM in Asia was also highlighted in the editorial section of the same issue [2]. Because regional data on transmission networks remain largely inadequate, we examined the population history of HIV-1 transmission networks by estimating the temporal origin of genetically similar virus variants circulating at a population level across Asia. Using phylodynamic information, we also attempted
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to explain the continued expansion of HIV-1 among MSM as seen today in the region. We studied 192 HIV-1 positive treatment-naive MSM recruited in Singapore and Malaysia between 2006 and 2012. The protease sequence data generated from an antiretroviral resistance surveillance program were analyzed using neighbor-joining and maximum likelihood phylogenetic reconstructions to identify transmission networks, following guidelines described elsewhere [3, 4]. Bayesian coalescent analysis was carried out to delineate the divergence time of each networks. A total of 12 transmission networks of different sizes (involving 3– 23 MSM subjects) were identified in Singapore and Malaysia, most of which emerged after the mid-1990s (Figure 1). New networks continued to emerge thereafter, despite increased access to combination antiretroviral therapy in both of these countries. Branch length analysis of the time-stamped phylogenetic trees also showed a relatively short transmission interval (time between transmission events), ranged from 0.1 to 6.5 years, suggesting that HIV-1 was transmitted at great speed within these networks. Similar phylodynamic studies conducted recently in China and Hong Kong also uncovered the presence of multiple transmission networks among MSM [6, 7] (Figure 1). Population history estimation for HIV-1 showed a trend of continuous emergence of new networks and coexistence of multiple MSM subepidemics from various common ancestors in these Asian countries. This is in alignment with the high HIV-1 incidence among MSM reported across Asia [8], establishing the role of transmission networks in contributing to the rise in new HIV-1 infections. These networks, if left uninterrupted by means of effective intervention strategies, such as early initiation of combination antiretroviral therapy or preexposure prophylaxis, will most likely continue to grow, resulting in sustained transmission among MSM.
Figure 1. Divergence times of human immunodeficiency virus type 1 (HIV-1) transmission networks among men who have sex with men in Asia. The divergence time (in calendar years) of the most recent common ancestor for the transmission networks observed in Malaysia and Singapore were estimated based on the HIV-1 protease gene using Bayesian coalescent relaxed clock-based analysis in BEAST software (version 1.7.4) [5] and a general time-reversible nucleotide substitution model with a gamma distribution and a proportion of invariant sites. Under similar conditions, the origin of the transmission networks found in Hong Kong and mainland China (northern China) were estimated based on the HIV-1 pol and gag gene sequences, respectively, also using BEAST software. The mean divergence times (circles) for each transmission network and the 95% highest posterior distribution are indicated.
Note Potential conflicts of interest. All authors: No reported conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.
Kim Tien Ng,1 Kah Ying Ng,2 Jonathan Hon-Kwan Chen,3,4 Oon Tek Ng,2 Adeeba Kamarulzaman,1 and Kok Keng Tee1
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Centre of Excellence for Research in AIDS (CERiA), Department of Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia; 2 Institute of Infectious Disease and Epidemiology, Communicable Disease Centre, Tan Tock Seng Hospital, Singapore; 3Department of Microbiology, Queen Mary Hospital, and 4AIDS Institute, University of Hong Kong, Hong Kong Special Administrative Region, China
References 1. Yang HT, Tang W, Xiao ZP, et al. Worsening epidemic of HIV and syphilis among men who have sex with men in Jiangsu Province, China. Clin Infect Dis 2014; 58:1753–9. 2. Mayer KH. The next tsunami? HIV spread in Asian men who have sex with men. Clin Infect Dis 2014; 58:1760–2. 3. Aldous JL, Pond SK, Poon A, et al. Characterizing HIV transmission networks across the United States. Clin Infect Dis 2012; 55:1135–43. 4. Chalmet K, Staelens D, Blot S, et al. Epidemiological study of phylogenetic transmission
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clusters in a local HIV-1 epidemic reveals distinct differences between subtype B and non-B infections. BMC Infect Dis 2010; 10:262. Drummond AJ, Rambaut A. BEAST: Bayesian evolutionary analysis by sampling trees. BMC Evol Biol 2007; 7:214. Chen JH, Wong KH, Chan KC, et al. Phylodynamics of HIV-1 subtype B among the menhaving-sex-with-men (MSM) population in Hong Kong. PLoS One 2011; 6:e25286. Ye J, Xin R, Yu S, et al. Phylogenetic and temporal dynamics of human immunodeficiency virus type 1 CRF01_AE in China. PLoS One 2013; 8:e54238. Joint United Nations Programme on HIV/AIDS. HIV in Asia and the Pacific. Available at: http:// www.unaids.org/en/resources/documents/2013/ name,89768,en.asp. Accessed 3 July 2014.
Correspondence: Kok Keng Tee, PhD, Centre of Excellence for Research in AIDS (CERiA), Department of Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia ([email protected]). Clinical Infectious Diseases 2014;59(6):910–11 © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals. [email protected]. DOI: 10.1093/cid/ciu480
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to explain the continued expansion of HIV-1 among MSM as seen today in the region. We studied 192 HIV-1 positive treatment-naive MSM recruited in Singapore and Malaysia between 2006 and 2012. The protease sequence data generated from an antiretroviral resistance surveillance program were analyzed using neighbor-joining and maximum likelihood phylogenetic reconstructions to identify transmission networks, following guidelines described elsewhere [3, 4]. Bayesian coalescent analysis was carried out to delineate the divergence time of each networks. A total of 12 transmission networks of different sizes (involving 3– 23 MSM subjects) were identified in Singapore and Malaysia, most of which emerged after the mid-1990s (Figure 1). New networks continued to emerge thereafter, despite increased access to combination antiretroviral therapy in both of these countries. Branch length analysis of the time-stamped phylogenetic trees also showed a relatively short transmission interval (time between transmission events), ranged from 0.1 to 6.5 years, suggesting that HIV-1 was transmitted at great speed within these networks. Similar phylodynamic studies conducted recently in China and Hong Kong also uncovered the presence of multiple transmission networks among MSM [6, 7] (Figure 1). Population history estimation for HIV-1 showed a trend of continuous emergence of new networks and coexistence of multiple MSM subepidemics from various common ancestors in these Asian countries. This is in alignment with the high HIV-1 incidence among MSM reported across Asia [8], establishing the role of transmission networks in contributing to the rise in new HIV-1 infections. These networks, if left uninterrupted by means of effective intervention strategies, such as early initiation of combination antiretroviral therapy or preexposure prophylaxis, will most likely continue to grow, resulting in sustained transmission among MSM.
Figure 1. Divergence times of human immunodeficiency virus type 1 (HIV-1) transmission networks among men who have sex with men in Asia. The divergence time (in calendar years) of the most recent common ancestor for the transmission networks observed in Malaysia and Singapore were estimated based on the HIV-1 protease gene using Bayesian coalescent relaxed clock-based analysis in BEAST software (version 1.7.4) [5] and a general time-reversible nucleotide substitution model with a gamma distribution and a proportion of invariant sites. Under similar conditions, the origin of the transmission networks found in Hong Kong and mainland China (northern China) were estimated based on the HIV-1 pol and gag gene sequences, respectively, also using BEAST software. The mean divergence times (circles) for each transmission network and the 95% highest posterior distribution are indicated.
Note Potential conflicts of interest. All authors: No reported conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.
Kim Tien Ng,1 Kah Ying Ng,2 Jonathan Hon-Kwan Chen,3,4 Oon Tek Ng,2 Adeeba Kamarulzaman,1 and Kok Keng Tee1
5.
6.
7.
1
Centre of Excellence for Research in AIDS (CERiA), Department of Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia; 2 Institute of Infectious Disease and Epidemiology, Communicable Disease Centre, Tan Tock Seng Hospital, Singapore; 3Department of Microbiology, Queen Mary Hospital, and 4AIDS Institute, University of Hong Kong, Hong Kong Special Administrative Region, China
References 1. Yang HT, Tang W, Xiao ZP, et al. Worsening epidemic of HIV and syphilis among men who have sex with men in Jiangsu Province, China. Clin Infect Dis 2014; 58:1753–9. 2. Mayer KH. The next tsunami? HIV spread in Asian men who have sex with men. Clin Infect Dis 2014; 58:1760–2. 3. Aldous JL, Pond SK, Poon A, et al. Characterizing HIV transmission networks across the United States. Clin Infect Dis 2012; 55:1135–43. 4. Chalmet K, Staelens D, Blot S, et al. Epidemiological study of phylogenetic transmission
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clusters in a local HIV-1 epidemic reveals distinct differences between subtype B and non-B infections. BMC Infect Dis 2010; 10:262. Drummond AJ, Rambaut A. BEAST: Bayesian evolutionary analysis by sampling trees. BMC Evol Biol 2007; 7:214. Chen JH, Wong KH, Chan KC, et al. Phylodynamics of HIV-1 subtype B among the menhaving-sex-with-men (MSM) population in Hong Kong. PLoS One 2011; 6:e25286. Ye J, Xin R, Yu S, et al. Phylogenetic and temporal dynamics of human immunodeficiency virus type 1 CRF01_AE in China. PLoS One 2013; 8:e54238. Joint United Nations Programme on HIV/AIDS. HIV in Asia and the Pacific. Available at: http:// www.unaids.org/en/resources/documents/2013/ name,89768,en.asp. Accessed 3 July 2014.
Correspondence: Kok Keng Tee, PhD, Centre of Excellence for Research in AIDS (CERiA), Department of Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia ([email protected]). Clinical Infectious Diseases 2014;59(6):910–11 © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals. [email protected]. DOI: 10.1093/cid/ciu480
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