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Current HIV Research


ISSN (Print): 1570-162X
ISSN (Online): 1873-4251

Research Article

Molecular Characterization of HIV-1 Minority Subtypes in Hong Kong: A Recent Epidemic of CRF07_BC among the Men who have Sex with Men Population

Author(s): Kenneth Siu-Sing Leung, Sabrina Wai-Chi To, Jonathan Hon-Kwan Chen, Gilman Kit-Hang Siu, Kenny Chi-Wai Chan and Wing-Cheong Yam*

Volume 17, Issue 1, 2019

Page: [53 - 64] Pages: 12

DOI: 10.2174/1570162X17666190530081355


Background: Over the past years, an increasing trend was noticed for non-B and non- CRF01_AE HIV-1 strains prevalence in Hong Kong.

Objective: In this study, we aimed at using the available HIV-1 pol sequences collected from 1994 to 2013 through our local antiretroviral resistance surveillance program to investigate the molecular epidemiology and evolution of HIV-1 minority subtypes in Hong Kong. We also aimed at investigating their potential association and impact of those transmission risk groups.

Methods: A total of 2,315 HIV-1 partial pol sequences were included. HIV-1 genotypes were determined by REGA Genotyping Tool and phylogenetic analysis with reference sequences. The viral evolutionary rates and time of the most common ancestor (tMRCA) were estimated by Bayesian Markov Chain Monte Carlo (MCMC) interference.

Results: Apart from the two prevalent HIV-1 genotypes in Hong Kong (subtype B,41.6%, CRF01_AE,40.5%), phylogenetic analysis revealed a broad viral diversity including CRF07_BC(5.1%), subtype C(4.5%), CRF02_AG(1.1%), CRF08_BC(0.8%), subtype A1(0.8%), subtype G(0.4%), subtype D(0.4%), CRF06_cpx(0.4%), subtype F(0.1%), CRF12_BF(0·04%) and other recombinants(4.5%). The top five minority subtypes were further analyzed which demonstrated distinct epidemiological and phylogenetic patterns. Over 70% of subtypes A1, C and CRF02_AG infections were circulated among non-Chinese Asians or African community in Hong Kong and were mainly transmitted between heterosexual regular partners. Instead, over 90% of CRF07_BC and CRF08_BC patients were Chinese. An epidemic cluster was identified in CRF07_BC and estimated to expand from 2002 onwards based on skyline plot and molecular clock analysis.

Conclusion: Our results highlighted the emergence of CRF07_BC epidemic in local MSM community, public health interventions targeting the community should be further enhanced to tackle the epidemic.

Keywords: HIV-1 epidemiology, CRF07_BC, HIV-1 minority subtypes, non-B non-AE transmission, men-who-have-sexwith- men, HIV-1 partial pol gene.

Graphical Abstract
WHO U. Global report: UNAIDS Report on the global AIDS epidemic. 2013. global_ report/en/
Han X, An M, Zhang M, et al. Identification of 3 distinct HIV-1 founding strains responsible for expanding epidemic among men who have sex with men in 9 Chinese cities. J Acquir Immune Defic Syndr 2013; 64(1): 16-24.
[] [PMID: 23542640]
van Griensven F, Holtz TH, Thienkrua W, et al. Temporal trends in HIV-1 incidence and risk behaviours in men who have sex with men in Bangkok, Thailand, 2006-13: an observational study. Lancet HIV 2015; 2(2): e64-70.
[] [PMID: 26424462]
van Griensven F, Guadamuz TE, de Lind van Wijngaarden JW, Phanuphak N, Solomon SS, Lo YR. Challenges and emerging opportunities for the HIV prevention, treatment and care cascade in men who have sex with men in Asia Pacific. Sex Transm Infect 2017; 93(5): 356-62.
[] [PMID: 28729520]
Virtual AIDS Office of Hong Kong DoHHKS HIV Surveillance Report 2014.
Strathdee SA, Stockman JK. Epidemiology of HIV among injecting and non-injecting drug users: current trends and implications for interventions. Curr HIV/AIDS Rep 2010; 7(2): 99-106.
[] [PMID: 20425564]
Hemelaar J, Gouws E, Ghys PD, Osmanov S. Global trends in molecular epidemiology of HIV-1 during 2000-2007. AIDS 2011; 25(5): 679-89.
[] [PMID: 21297424]
Pyne MT, Hackett J Jr, Holzmayer V, Hillyard DR. Large-scale analysis of the prevalence and geographic distribution of HIV-1 non-B variants in the United States. J Clin Microbiol 2013; 51(8): 2662-9.
[] [PMID: 23761148]
Taylor BS, Sobieszczyk ME, McCutchan FE, Hammer SM. The challenge of HIV-1 subtype diversity. N Engl J Med 2008; 358(15): 1590-602.
[] [PMID: 18403767]
Cheung KW, Peng Q, He L, et al. Rapid and Simultaneous Detection of Major Drug Resistance Mutations in Reverse Transcriptase Gene for HIV-1 CRF01_AE, CRF07_BC and Subtype B in China Using Sequenom MassARRAY® System. PLoS One 2016; 11(4): e0153641.
[] [PMID: 27092551]
To SW, Chen JH, Wong KH, Chan KC, Chen Z, Yam WC. Determination of the high prevalence of Dual/Mixed- or X4-tropism among HIV type 1 CRF01_AE in Hong Kong by genotyping and phenotyping methods. AIDS Res Hum Retroviruses 2013; 29(8): 1123-8.
[] [PMID: 23647565]
Xiao P, Li J, Fu G, Zhou Y, Huan X, Yang H. Geographic Distribution and Temporal Trends of HIV-1 Subtypes through Heterosexual Transmission in China: A Systematic Review and Meta-Analysis. Int J Environ Res Public Health 2017; 14(7): E830.
[] [PMID: 28737729]
Leung TW, Mak D, Wong KH, et al. Molecular epidemiology demonstrated three emerging clusters of human immunodeficiency virus type 1 subtype B infection in Hong Kong. AIDS Res Hum Retroviruses 2008; 24(7): 903-10.
[] [PMID: 18593342]
Chen JHK, Wong KH, Chen Z, et al. Increased genetic diversity of HIV-1 circulating in Hong Kong. PLoS One 2010; 5(8): e12198.
[] [PMID: 20808942]
Tee KK, Pybus OG, Li XJ, et al. Temporal and spatial dynamics of human immunodeficiency virus type 1 circulating recombinant forms 08_BC and 07_BC in Asia. J Virol 2008; 82(18): 9206-15.
[] [PMID: 18596096]
Chen YJ, Lee CM, Chen M, et al. Molecular epidemiology of HIV-1 infection in Taiwan from 2005 to 2008: further spread of CRF07_BC and emergence of CRF07_BC/subtype B dual infection. J Acquir Immune Defic Syndr 2012; 59(5): 438-46.
[] [PMID: 22343173]
Zhang M, Jia D, Li H, et al. Phylodynamic analysis revealed that epidemic of CRF07_BC strain in men who have sex with men drove its second spreading wave in China. AIDS Res Hum Retroviruses 2017; 33(10): 1065-9.
[] [PMID: 28569547]
Jiao Y, Wang Y, Kong D, et al. Characterization of a new HIV-1 CRF01_AE/CRF07_BC recombinant virus form among men who have sex with men in beijing, China. AIDS Res Hum Retroviruses 2018; 34(6): 550-4.
[] [PMID: 29589485]
Chen JH, Wong KH, Chan K, et al. Evaluation of an in-house genotyping resistance test for HIV-1 drug resistance interpretation and genotyping. J Clin Virol 2007; 39(2): 125-31.
[] [PMID: 17449318]
Chen JH, Wong KH, Li PC, et al. In-house human immunodeficiency virus-1 genotype resistance testing to determine highly active antiretroviral therapy resistance mutations in Hong Kong. Hong Kong Med J 2012; 18(1): 20-4.
[PMID: 22302906]
Chen JH, Wong KH, Chan KC, et al. Molecular epidemiology and divergence of HIV type 1 protease codon 35 inserted strains among treatment-naive patients in Hong Kong. AIDS Res Hum Retroviruses 2008; 24(4): 537-42.
[] [PMID: 18426335]
Lee SS, Tam DK, Tan Y, et al. An exploratory study on the social and genotypic clustering of HIV infection in men having sex with men. AIDS 2009; 23(13): 1755-64.
[] [PMID: 19609202]
Staden R, Beal KF, Bonfield JK. The Staden package, 1998. Methods Mol Biol 2000; 132: 115-30.
[PMID: 10547834]
Bonfield JK. Smith Kf, Staden R. A new DNA sequence assembly program. Nucleic Acids Res 1995; 23(24): 4992-9.
[] [PMID: 8559656]
de Oliveira T, Deforche K, Cassol S, et al. An automated genotyping system for analysis of HIV-1 and other microbial sequences. Bioinformatics 2005; 21(19): 3797-800.
[] [PMID: 16076886]
Guindon S, Dufayard JF, Lefort V, Anisimova M, Hordijk W, Gascuel O. New algorithms and methods to estimate maximum-likelihood phylogenies: assessing the performance of PhyML 3.0. Syst Biol 2010; 59(3): 307-21.
[] [PMID: 20525638]
Kuiken C, Korber B, Shafer RW. HIV sequence databases. AIDS Rev 2003; 5(1): 52-61.
[PMID: 12875108]
Lefort V, Longueville JE, Gascuel O. SMS: Smart Model Selection in PhyML. Mol Biol Evol 2017; 34(9): 2422-4.
[] [PMID: 28472384]
Guindon S, Gascuel O. A simple, fast, and accurate algorithm to estimate large phylogenies by maximum likelihood. Syst Biol 2003; 52(5): 696-704.
[] [PMID: 14530136]
Susko E. Using minimum bootstrap support for splits to construct confidence regions for trees. Evol Bioinform Online 2007; 2: 129-43.
[PMID: 19455207]
Posada D. jModelTest: phylogenetic model averaging. Mol Biol Evol 2008; 25(7): 1253-6.
[] [PMID: 18397919]
Darriba D, Taboada GL, Doallo R, Posada D. jModelTest 2: more models, new heuristics and parallel computing. Nat Methods 2012; 9(8): 772.
[] [PMID: 22847109]
Drummond AJ, Rambaut A. BEAST: Bayesian evolutionary analysis by sampling trees. BMC Evol Biol 2007; 7: 214.
[] [PMID: 17996036]
Bouckaert R, Heled J, Kühnert D, et al. BEAST 2: a software platform for Bayesian evolutionary analysis. PLOS Comput Biol 2014; 10(4): e1003537.
[] [PMID: 24722319]
Rambaut A, Drummond AJ, Xie D, Baele G, Suchard MA. Posterior Summarization in Bayesian Phylogenetics Using Tracer 1.7. Syst Biol 2018; 67(5): 901-4.
[] [PMID: 29718447]
Su YZ, Ma YL, Jia MH, et al. Update on diversity and distribution of HIV-1 subtypes in Yunnan province. Epidemiol Infect 2013; 141(11): 2418-27.
[] [PMID: 23406836]
Sui H, Gui T, Jia L, et al. Different frequencies of drug resistance mutations among HIV-1 subtypes circulating in China: a comprehensive study. PLoS One 2014; 9(3): e91803.
[] [PMID: 24663120]
Yang R, Kusagawa S, Zhang C, Xia X, Ben K, Takebe Y. Identification and characterization of a new class of human immunodeficiency virus type 1 recombinants comprised of two circulating recombinant forms, CRF07_BC and CRF08_BC, in China. J Virol 2003; 77(1): 685-95.
[] [PMID: 12477871]
Li L, Lu X, Li H, et al. High genetic diversity of HIV-1 was found in men who have sex with men in Shijiazhuang, China. Infect Genet Evol 2011; 11(6): 1487-92.
[] [PMID: 21645646]
Li L, Sun G, Li T, et al. Multiple introductions of HIV into men who have sex with men were found in Zhengzhou City, China. AIDS Res Hum Retroviruses 2012; 28(9): 1147-51.
[] [PMID: 22236149]
Chen JH, Wong KH, Li P, et al. Molecular epidemiological study of HIV-1 CRF01_AE transmission in Hong Kong. J Acquir Immune Defic Syndr 2009; 51(5): 530-5.
[] [PMID: 19521252]
Chen JHK, Wong KH, Chan KCW, To SWC, Chen Z, Yam WC. Phylodynamics of HIV-1 subtype B among the men-having-sex-with-men (MSM) population in Hong Kong. PLoS One 2011; 6(9): e25286.
[] [PMID: 21966483]
Bhusal N, Sutthent R, Horthongkham N, Athipanyasilp N, Kantakamalakul W. Prevalence of HIV-1 subtypes and antiretroviral drug resistance mutations in Nepal. Curr HIV Res 2016; 14(6): 517-24.
[] [PMID: 27697032]
Oyomopito RA, Chen YJ, Sungkanuparph S, et al. Risk group characteristics and viral transmission clusters in South-East Asian patients infected with human immunodeficiency virus-1 (HIV-1) circulating recombinant form (CRF) 01_AE and subtype B. Kaohsiung J Med Sci 2015; 31(9): 445-53.
[] [PMID: 26362956]
Wei M, Guan Q, Liang H, et al. Simple subtyping assay for human immunodeficiency virus type 1 subtypes B, C, CRF01-AE, CRF07-BC, and CRF08-BC. J Clin Microbiol 2004; 42(9): 4261-7.
[] [PMID: 15365021]
Yan Y, Wu S, Chen L, et al. Shift in HIV/AIDS Epidemic in Southeastern China: A Longitudinal Study from 1987 to 2015. Int J Environ Res Public Health 2016; 13(8): E794.
[] [PMID: 27509511]
Ariën KK, Vanham G, Arts EJ. Is HIV-1 evolving to a less virulent form in humans? Nat Rev Microbiol 2007; 5(2): 141-51.
[] [PMID: 17203103]
Wilkinson E, Engelbrecht S, de Oliveira T. History and origin of the HIV-1 subtype C epidemic in South Africa and the greater southern African region. Sci Rep 2015; 5: 16897.
[] [PMID: 26574165]
Siddappa NB, Dash PK, Mahadevan A, et al. Identification of subtype C human immunodeficiency virus type 1 by subtype-specific PCR and its use in the characterization of viruses circulating in the southern parts of India. J Clin Microbiol 2004; 42(6): 2742-51.
[] [PMID: 15184461]
Census and Statics Department TGoHKS. 2013. Available at: https://www.
Piyasirisilp S, McCutchan FE, Carr JK, et al. A recent outbreak of human immunodeficiency virus type 1 infection in southern China was initiated by two highly homogeneous, geographically separated strains, circulating recombinant form AE and a novel BC recombinant. J Virol 2000; 74(23): 11286-95.
[] [PMID: 11070028]
Feng Y, Takebe Y, Wei H, et al. Geographic origin and evolutionary history of China’s two predominant HIV-1 circulating recombinant forms, CRF07_BC and CRF08_BC. Sci Rep 2016; 6: 19279.
[] [PMID: 26763952]
Su L, Graf M, Zhang Y, et al. Characterization of a virtually full-length human immunodeficiency virus type 1 genome of a prevalent intersubtype (C/B′) recombinant strain in China. J Virol 2000; 74(23): 11367-76.
[] [PMID: 11070037]
Zhang L, Chen Z, Cao Y, et al. Molecular characterization of human immunodeficiency virus type 1 and hepatitis C virus in paid blood donors and injection drug users in china. J Virol 2004; 78(24): 13591-9.
[] [PMID: 15564470]
Lin HH, Shih YL, Liu YC, et al. An epidemic of HIV type I CRF07_BC infection among injection drug users in Taiwan. J Acquir Immune Defic Syndr 2006; 42(2): 248-55.
[] [PMID: 16760801]
Li XJ, Kusagawa S, Xia X, et al. Molecular epidemiology of the heterosexual HIV-1 transmission in Kunming, Yunnan Province of China suggests origin from the local IDU epidemic. AIDS Res Hum Retroviruses 2005; 21(11): 977-80.
[] [PMID: 16386117]
Qiu Z, Xing H, Wei M, et al. Characterization of five nearly full-length genomes of early HIV type 1 strains in Ruili city: implications for the genesis of CRF07_BC and CRF08_BC circulating in China. AIDS Res Hum Retroviruses 2005; 21(12): 1051-6.
[] [PMID: 16379609]
Li Z, Liao L, Feng Y, et al. Trends of HIV subtypes and phylogenetic dynamics among young men who have sex with men in China, 2009-2014. Sci Rep 2015; 5: 16708.
[] [PMID: 26577039]
He X, Xing H, Ruan Y, et al. A comprehensive mapping of HIV-1 genotypes in various risk groups and regions across China based on a nationwide molecular epidemiologic survey. PLoS One 2012; 7(10): e47289.
[] [PMID: 23056619]
Meng Z, Xing H, He X, Ma L, Xu W, Shao Y. Genetic characterization of three newly isolated CRF07_BC near full-length genomes in China. AIDS Res Hum Retroviruses 2007; 23(8): 1049-54.
[] [PMID: 17725423]
Jia Y, Sun J, Fan L, et al. Estimates of HIV prevalence in a highly endemic area of China: Dehong Prefecture, Yunnan Province. Int J Epidemiol 2008; 37(6): 1287-96.
[] [PMID: 18922804]
Takebe Y, Liao H, Hase S, et al. Reconstructing the epidemic history of HIV-1 circulating recombinant forms CRF07_BC and CRF08_BC in East Asia: the relevance of genetic diversity and phylodynamics for vaccine strategies. Vaccine 2010; 28(Suppl. 2): B39-44.
[] [PMID: 20510742]
Li X, Xue Y, Cheng H, et al. HIV-1 Genetic Diversity and Its Impact on Baseline CD4+T Cells and Viral Loads among Recently Infected Men Who Have Sex with Men in Shanghai, China. PLoS One 2015; 10(6): e0129559.
[] [PMID: 26121491]
Beyrer C, Baral SD, van Griensven F, et al. Global epidemiology of HIV infection in men who have sex with men. Lancet 2012; 380(9839): 367-77.
[] [PMID: 22819660]
Jakopanec I, Grjibovski AM, Nilsen Ø, Blystad H, Aavitsland P. Trends in HIV infection surveillance data among men who have sex with men in Norway, 1995-2011. BMC Public Health 2013; 13: 144.
[] [PMID: 23414557]
Li HM, Peng RR, Li J, et al. HIV incidence among men who have sex with men in China: a meta-analysis of published studies. PLoS One 2011; 6(8): e23431.
[] [PMID: 21887251]
Koblin BA, Husnik MJ, Colfax G, et al. Risk factors for HIV infection among men who have sex with men. AIDS 2006; 20(5): 731-9.
[] [PMID: 16514304]
Baral S, Trapence G, Motimedi F, et al. HIV prevalence, risks for HIV infection, and human rights among men who have sex with men (MSM) in Malawi, Namibia, and Botswana. PLoS One 2009; 4(3): e4997.
[] [PMID: 19325707]
Balaji AB, Bowles KE, Le BC, Paz-Bailey G, Oster AM, Group NS. High HIV incidence and prevalence and associated factors among young MSM, 2008. AIDS 2013; 27(2): 269-78.
[] [PMID: 23079807]

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