MSM and HIV-1 infection in China

Addressing HIV-1/AIDS problem in China's complex socioeconomic environment has never been straightforward. Dynamic economic changes over the past few decades continue to create new challenges to intervention efforts, particularly among one of the worst hit and hardest to reach populations, men who have sex with men (MSM). MSM represents a diverse population coming from all walks of life and largely resides in urban settings. Increasing proportion has been coming from young and well-educated professionals, including college students. Developing effective intervention measures to target MSM has become critical to China's HIV-1/AIDS prevention efforts. Not only does recent data indicate that HIV-1 infections have been rising rapidly among the MSM in China, but studies have shown that Chinese MSM commonly participate in high-risk behaviors that make this population a potential bridge for generalized disease transmission. Comprehensive, coordinated and creative strategies from the key stake holders have to be implemented and reinforced in a timely fashion before the epidemic runs out of control and further spread into the general population. HIV-1/AIDS in China was initially identified among populations of intravenous drug users (IDUs) in southwest provinces in 1980's and commercial blood donors in central provinces in 1990's [1,2]. Collaborative public health initiatives over the past decade have stopped transmission through illegal blood donation, transfusion and reduced the spread of HIV-1 among IDUs, but infections among MSM continue to rise at alarming rates [2–6]. According to statistics from the Chinese Ministry of Health and UNAIDS [7], MSM comprised only 0.3% of the all cases between 1985 and 2005. This number spiked to 2.5% in 2006, and reached 25.8% in 2014 (Fig. 1). More strikingly, between 2007 and 2009, the proportion of MSM among the new HIV-1 cases jumped from 12.2% to 32.5% [7]. A 2009 national survey of MSM in over 61 major cities found a prevalence as high as 10% in major southwestern cities where the epidemic was first identified, compared to an average prevalence of 5% overall [7]. We recently undertook a perspective study of 8943 MSM in 11 major Chinese cities and showed the average prevalence of HIV-1 infection to be 9.9% with average incidence of 5.5 per 100 person-years (/100PY), a startling number similar to those reported elsewhere [8–10] and notably higher than that of female sex workers (1.4/100PY) and IDUs (0.7/100PY) in China [11]. Considering China's size and widespread population, national statistics can fail to reflect the severity of localized epidemics. For instance, in one northeastern city, Shenyang, HIV-1 incidence rose from 4.7/100 PY to as high as 10.2/100PY between 2007 and 2009 [12]. These cases were also associated with high incidence of syphilis infections, with an average 38.5/100 PY [13]. HIV-1 transmission in China is increasing faster in MSM than in any other group. The rates of high-risk behavior among MSM are particularly concerning. We found that about 22.9% of the infected MSM have a history of blood donation, increasing likelihood of HIV-1 transmission through blood products. A very low proportion of HIV-1 positive individuals share their status with sexual partners, 44.1% to 43.9% to couples and regular male sexual partners, and only 4.9% to casual male sexual partners. Approximately 38.0% of MSM have exchanged money for sexual activities. An estimated 45.7% of MSM reported having unprotected sex with homosexual partners, and 10.9% with heterosexual partners. Although drug use has not been shown to be a significant contributor to HIV transmission between Chinese MSM, research in seven major cities showed that districts with highest rates of illicit drug use among MSM populations also shared the highest HIV prevalence [14,15]. Such high-risk behavior not only makes MSM populations significantly more vulnerable to infection, but also creates an open door for disease transmission to the general population. Genetic and biological properties of HIV-1 have become increasingly complex among MSM. While the initial dominant subtype of HIV-1 among MSM closely resembles European-North American subtype B and Thai subtype B (B′), our recent studies have shown the dominance of Thai circulating recombinant form (CRF) 01_AE in both acutely and chronically infected MSM (Fig. 2). In the acute cohort, CRF01_AE is responsible for 52.2% to 75.9% of infected MSM studied from 2007 to 2009. In the chronic cohort, approximately 81.3% of infections were caused by CRF01_AE, whereas subtypes B or B′ and C/CRF07/CRF08 are responsible for 16.0% and 2.7%, respectively. Several unique recombinant forms (URF) have also been identified in the MSM population as the result of co-infection by and recombination between different subtypes of HIV-1. These results are consistent with the hypothesis that HIV-1 was introduced to MSM via multiple high-risk groups from both within and outside China and continue to evolve to more complexity [1,16]. Furthermore, many of these viruses are resistant to one or more antiretroviral drugs, contributing to the high prevalence of HIV-1 drug resistance strains in MSM populations [17–21]. Among the 10 Chinese cities we studied, the greatest prevalence was found in Kunming (14.3%), Shenyang (8.3%), Beijing (7.5%) and Chongqing (4.6%). Lastly, significant proportion of viruses circulating among MSM also demonstrated strong resistance to recently identified broadly neutralizing monoclonal antibodies, suggesting their unique antigenic features compared to those prevalent elsewhere in the world. As the epidemic continues to expand throughout the MSM and inevitably spills over to other populations, such genetic diversity and levels of resistance are expected to increase, creating further challenges to effective antiretroviral treatment and vaccine development. While historically, homosexual behavior was not condemned in China, economic and cultural factors have pressured MSM populations to hide their sexual identity [3]. Traditional attitudes towards sex have largely been influenced by Chinese Confucian philosophies which emphasize obedience to one's family and sex within marriage for the purpose of reproduction. In recent decades, however, there has been a decline in the strength of these traditional forces, a major source of which lies in the liberal economic and political reforms which began in the late 1970's. In fact, modern Chinese society has undergone a dramatic sexual liberation, with increasing rates of pre-marital and extramarital sex and a growing tolerance of homosexual behavior. Bars and public spaces targeting homosexuals have become more common in major cities, and the internet and mobile application (APP) has provided an outlet for MSM to privately access information and connect with other MSM communities [11]. Nonetheless, despite these more liberal attitudes, homosexuality remains highly stigmatized. Chinese society emphasizes the importance of social standing, and many MSM cite a fear of ‘losing face’, meaning damage to their social integrity, if their sexual orientation were revealed. The primary pressure for homosexuals to conceal their identity comes from their families, in which younger generations are expected to marry to uphold the family reputation and lineage. Behavioral surveys of Chinese MSM have reported that between 20.0% and 31.2% Chinese MSM are married with females. These numbers vary across cities, with 19.5% reported in Shenyang and 20.5% in Beijing. However, married homosexual men commonly hide their sexual behavior, having significantly higher proportion of commercial sexual behaviors with male partners (18.3% vs. 12.2%), alcohol use (27.1% vs. 13.1%), illicit drug use (5.3% vs. 2.5%) and HIV prevalence (5.4% vs. 3.8%) than men who only have sex with men, thus putting their wives and children at risk of becoming infected with HIV-1 and other sexually transmitted diseases. Adding to this complexity is the movement of approximately 140 million migrants from rural areas to large cities to seek for financial prosperity, a byproduct of China's rapid economic development [22]. Migrant MSM populations have a higher prevalence of HIV-1 infections compared to non-migrants as migrant MSM generally perceive themselves to have a lower risk for contracting HIV-1. Thus, they frequently engage in high-risk behaviors by having low rates of condom use and more sexual partners. Not only does this mobile demographic facilitate HIV-1 transmission between Chinese cities, but most migrants move ‘illegally’, restricting their access to public health services such as HIV-1 testing and treatment outside their hometown. Phylogenetic tree depicting the genetic complexity of HIV-1 from infected MSM in China. A total of 197 full-length pol nucleotide sequences (2844 nucleotides in length located between position 2253–5096 in the HXB2 genome) obtained from the Chinese MSM between year 2007 and 2013 were included with appropriate reference sequences from HIV database (http://hiv-web.lan1.gov/). Individual sequences clustered with CRF01_AE are colored in red, subtype B/B′ in green, subtype CRF07_BC in blue while the reference sequences are in black. The remaining CRFs and URFs are highlighted with various other colors. Rapid changes in the demographic profile of Chinese MSM and the biological complexity of HIV-1 pose tremendous challenges to prevention strategies, antiretroviral therapies and vaccine development. Although HIV-1/AIDS is currently a low-level epidemic primarily localized among high-risk groups in specific geographic areas, generalized spread of the disease would be a tremendous public health crisis. Awareness that MSM may act as the vehicle for disease transmission beyond high-risk groups has made addressing this population a priority for both government and non-government prevention efforts [2]. In light of these dramatic changes, prevention and treatment strategies must be specifically tailored to reduce new infections among MSM and prevent generalization of the epidemic. Based on our study and previous research, we believe the following measures comprise the most effective approach towards this objective. At the policy level: Although China's State Council approved the ‘Regulation on the Prevention and Treatment of HIV-1/AIDS’ in 2006 which outlined recommendations to eliminate legal and public prejudices against infected individuals, it currently does not carry any specific legal consequences. New legislation is necessary which would provide clear legal requirements and enforcement policies, and should also be expanded to criminalize the intentional exposure of others to HIV-1 and require both physician and partner notification of an individual's HIV-1 positive status. At the program level: Increasing public education on and awareness of HIV-1/AIDS has shown to positively affect behavioral changes, and these campaigns need to be substantially targeted at Chinese MSM population. Our studies have shown that a majority of MSM prefer connecting via internet, mobile phones and other modern social media. Health campaigns should therefore utilize these new technologies and target the online chat rooms and resources frequently accessed by this population. The context of these programs should focus on promoting condom use and those proven effective preventive measures, as well as encouraging individuals and communities take responsibility for safe decisions. To raise awareness for these programs, popular regional and local figures affected by HIV-1/AIDS should be encouraged to take on leadership positions and act as role models for behavioral change. In particular, MSM population as a whole must recognize the seriousness and consequence of the situation should the status quo remains the same and has to lead the way to make drastic behavior change to minimize the further spread of HIV-1 in the population. At the research and clinical care level: Epidemiological research has increased in recent years; however, data need to be improved and applied to public health ends rather than held purely for surveillance and analysis. Proactive, voluntary testing and counseling services should be extended into outreach campaigns that specifically target MSM population, in order to ensure individuals know their status and receive clinical treatment and care in a timely manner. In conjunction with research showing that focusing antiretroviral treatments on high-risk HIV-1 positive groups can significantly reduce viral transmission [23–26], China should take steps to ensure MSM are receiving antiretroviral therapy and preventative strategies, such as pre-exposure prophylaxis [27]. Vaccine strategies should also be targeted to the HIV-1 strains that are dominant in MSM population. In countries worldwide, efforts to control HIV-1/AIDS among MSM face challenges similar to those found in China. In the United States, differences in access to medical care, reception of treatment and knowledge of partner status have been some of the greatest contributors to racial disparity in infections rates [28]. In many Latin American and African nations, as in China, fear of exposures due to stigmas surrounding HIV-1/AIDS or homosexuality remains the primary barrier to testing and treatment [29]. While the individual recommendations outlined here have shown great promise on the micro-scale, only through a large-scale, coordinated effort between policy, program, research and clinical sectors will we begin to see a significant reduction in new infections. The HIV-1/AIDS challenge is not insurmountable, but it will require streamlined and timely action. The authors thank Drs Xiaoxu Han and Junjie Xu for phylogenetic and epidemiologic analysis and Ms Jessica Spero Li and Kelly C. Arledge for technical assistance. This work was supported by the funds from National Natural Science Foundation Award 81530065, the National Science and Technology Major Projects (2012ZX10001-006 and 2012ZX10001-009), Ministry of Science and Technology of China (2014CB542500-03), China Program of the Bill & Melinda Gates Foundation, and partially by Janssen Investigator Award to Linqi Zhang.