MSM and HIV-1 infection in China

中国医科大学尚红教授和清华大学张林琦教授在今年10月27日的《国家科学评论》（National Science Review）杂志发表题为“MSM and HIV-1 infection in China”（中国男男同性恋人群与艾滋病感染）的评论文章，呼吁全社会高度重视艾滋病防治。特别是男男同性恋人群，现在已经到了全面爆发的边缘，必须及时采取有效防止措施。同时，加强基础研究，特别是根治策略和艾滋病疫苗的研究，为根本解决艾滋病重大难题提供有效的医学干预手段。
 
艾滋病防治在中国复杂的社会经济环境下向来不易。过去几十年里，经济发展的巨大变化使防治艾滋病不断面临新的挑战，特别对受害最深而又难以触及的男男同性恋人群（men who have sex with men, 下简称“MSM”）。
 



在中国，MSM遍布社会各阶层、各行各业，主要为城市居民，近年在高学历的年轻白领和在校大学生群体中亦有上升趋势。因此，针对MSM群体采取有效的干预治疗措施是中国防艾事业的关键一环。近来的数据显示，中国MSM群体中HIV感染率快速上升，普遍存在高风险的性行为，使MSM群体成为艾滋广泛传播的主要媒介。因此，关键利益相关者必须迅速贯彻执行全面而有效的战略举措，防止其进一步扩散到一般人群之中。
 
在中国，HIV/艾滋病最早出现于20世纪80年代南方的静脉注射吸毒群体以及90年代中部省份的卖血群体。过去十多年，完善的公共卫生法规已经消灭了由非法卖血与输血造成的HIV病毒传播，静脉注射吸毒者之间的传播也减少了。但是，MSM群体之间HIV病毒的传播却在不断飙升，而且速度惊人。


 

中国卫生部和联合国艾滋病规划署（UNAIDS）的数据显示，1985至2005年，中国艾滋感染者中，MSM群体中占感染总人数的0.3%，而到2006年攀升至2.5%，并继续飙升到2014年的25.8%（图1）。更惊人的是，从2007到2009，在新感染患者中，MSM人群从12.2%激增至32.5%。 2009年，一项在61个城市实施的全国性调查发现，南方几个主要城市MSM群体的HIV携带率普遍高达10%，远远高于全国平均5%的携带率。

 


最近，我们调查了中国11个主要城市、8943位有男男性行为的人士，发现其中感染率为9.9%，新发感染竟高达5.5每百人/年（编者注：100人中每年有5.5人新感染HIV）。这个惊人的数据与其他几个研究吻合，显著高于中国的女性性工作者（1.4 每百人/年）和静脉注射吸毒者（0.7每百人/年）。
 



考虑中国地大人多，全国性的统计很可能会忽略局部地区感染的严重程度。例如， 在沈阳，MSM人群HIV新发感染从2007年的4.7每百人/年增加到2009年的10.2每百人/年。这些新患者同时伴有高梅毒感染率，平均为38.5每百人/年。
 



MSM群体中一些高风险的行为特别值得关注。我们发现MSM群体中有22.9%的HIV感染者有献血史，这增加了通过血液制品传播艾滋的可能性。中国MSM群体中的HIV-1阳性携带者只有很少一部分（4.9%）对其同性偶然性伴侣告知感染状况，相比之下配偶和固定性伴侣的知情率为44.1%~43.9%。大约38.09%的MSM有过花钱买性的经历。据估计，有45.7%的MSM与同性发生过没有保护措施的性行为，与异性的数据为10.9% 。对于毒品使用，尽管没有发现对中国的MSM HIV传播有显著的贡献，对于国内7个大城市的调查发现，MSM的非法使用毒品的人群中，HIV感染率最高。这些高危行为不但使MSM群体更容易被感染，也为艾滋向一般人群传播打开了大门。
 





惊人的统计数据
 

在中国MSM群体中，HIV-1病毒的遗传特性和生物特征变得更加复杂。中国早期的主要病毒亚群接近于欧洲/北美的B亚型和泰国B亚型（B’）。我们最近研究发现，在MSM群体急性感染和慢性感染病例中，主要的病毒是泰国重组株（CRF）01_AE。


 

在急性期感染者队列中，CRF_01AE从2007年 占52.5%增加到2009年的75.9%。在慢性感染者队列中，大约81.3%的感染来自CRF_01AE，相比之下B和 B’亚型只占16%；C/CRF07/CRF08亚型只占2.7%。由于不同的HIV-1毒株亚型发生了共感染和重组，在中国MSM群体中产生几个独特的重组亚型。

 


这些结果显示，中国MSM群体中的HIV-1是通过国内国外的多个高危群体引入，并继续不断进化得更为复杂。而且，这些病毒中有不少对一种或几种抗逆转录病毒药物产生抗药性，导致MSM群体中的HIV耐药株的高流行性。在我们研究过的十个城市中，抗药性最高的是昆明（14.3%），后面依次是沈阳（8.3%）、北京（7.5%）和重庆（4.6%）。

 


最后，在MSM群体中流行的HIV病毒中，有相当一部分毒株对新近开发的广谱中和抗体显示出强烈的耐受性，说明这些HIV毒株具有不同于其他地区流行株的独特的抗原特征。鉴于HIV病毒不断在中国MSM群体中发展，并不可避免地扩散至其他人群，HIV病毒的遗传复杂性和抗药性也会不断增加，这给有效的抗逆转录病毒治疗和疫苗研发带来了更大的挑战。


 






独特的文化和社会经济特征
 



虽然从中国历史来看，同性性行为曾一度不受排斥，但是现代经济和文化因素仍使MSM群体隐藏其性取向。中国传统的性观念深受儒学影响，提倡家庭为重，主张以传宗接代为目的婚内性行为。近几十年来，随着20世纪70年代后期经济的迅猛发展，传统的性观念逐渐削弱。

 


事实上，现代中国社会正在经历一场惊骇世俗的性解放运动，婚前和婚外性行为增加，对同性性行为的理解和容忍也有了进步。针对同性恋者的酒吧和公共场所在大城市中越来越普遍，互联网和移动应用APP也为MSM群体提供了私下了解和接触其他同性群体的便利。

 


然而，尽管有这些开明的态度，同性恋还是被社会视为异端。中国社会崇尚社会地位，许多同性恋者不愿意暴露其真实的性倾向，怕丢“面子”，这可能会让自己的社会地位受损。同性恋遭受的主要压力来自家庭，老一辈期盼年轻一代结婚，维护家族的声誉与血统。


 


针对中国MSM群体的行为学调查指出，有20%到31.2%的MSM与女性结婚。这些数字因地不同，如沈阳为19.5%，而北京为20.5%。 然而，已婚的男同性恋者通常会隐藏自己的性倾向，与单纯男性性伴侣的人相比，他们花钱买同性性行为的比率更高（18.3% vs12.2%），吸毒（5.3% 对2.5%）和携带HIV的比率（5.4%比3.8%）也更高，从而把他们的妻子儿女置于HIV感染和其他性传播疾病的危险之中。
 



中国经济的快速发展也带来了1.4亿从农村到大城市寻求财富的打工族，这给MSM群体HIV问题添加了另一层的复杂性。与常住人口相比，流动人口的MSM人群HIV携带率较高，他们一般认为自己感染HIV的风险较低。因此，外来务工的MSM经常会有高危险的性行为，如不经常使用安全套和有更多的性伙伴。这种大规模人口流动不但帮助了HIV-1在城市间传播，而且绝大多数流动人口是“非法”迁徒，限制了他们正常享受公共健康设施的机会，如HIV-1检验和异地治疗等。
 









挑战与机会

 


中国MSM群体在人口学上的迅速变化和HIV-1病毒的生物复杂性给中国的防艾策略、抗逆转录病毒治疗和疫苗研发都带来巨大的挑战。虽然HIV/艾滋的疫情仍然处于低水平，主要局限在特定地域的高危群体之内，仍有可能出现大规模的流行性传染，并导致极大的公共健康危机。必须认识到，MSM群体可成为HIV在高危族群之外大范围传播的载体，MSM群体需要作为政府和非政府组织预防工作的优先重点。



 

针对上述变化，必须专门制定针对MSM群体预防和治疗策略，以减少MSM群体新发感染，防止疾病的大规模流行。根据我们的研究显示以下举措有利于防治艾滋的有效实现：
 


•政策层面： 

虽然国务院2006年批准的《艾滋病防治条例》已经明确规定，要求消除法律和公众对艾滋感染者的偏见，但目前并没有让违反者承担具体的法律后果。有必要制定新的法规，明确法律规定和执法政策，同时也要让故意传染他人HIV者承担法律责任，要求HIV-1阳性者必须向其性伴侣和医生告知其感染状态。

 



•宣传层面： 

加强公众教育，提高公众对民众关于HIV-1/艾滋的认识等举措已经显示出对行为变化的积极的影响，这类宣传应该更面向中国的MSM人群。我们的研究表明，MSM的主要联络方式是互联网、智能手机和其他现代社交媒介。

 


健康宣传教育应该更多地利用这些新技术，并针对网上聊天室和在线组群等这部分人经常使用的资源。宣传内容应着眼于促进安全套的使用以及已知的有效预防感染的措施，并鼓励个人和群体为自己的安全负责。


 


为了增加宣传的知名度，应该鼓励受HIV/艾滋感染的知名人士站出来现身说法，做出榜样。特别是男男性行为人群作为一个整体，必须认识到问题的严重性以及维持原状的后果将十分严重，只有采取措施改变其行为方式，才可能避免HIV-1在人群中的进一步扩散。
 




•研究和临床护理层面： 

流行病学研究虽然近年来有所增加，但数据应该更好地被利用，而非只用于监测和分析。预防性的无偿检测和咨询服务应该在宣传攻势中扩展到MSM群体。这样才能让这些人知道自己的状况，并及时接受治疗。


 

研究表明，抗逆转录病毒治疗可以大大降低高危群体中HIV-1的传染率，因此中国应采取措施确保MSM群体充分接受抗逆转录病毒疗法，并实施“预防性服药”等策略。 疫苗研发也必须针对MSM群体中占据主导的HIV-1的病毒亚群。



 


世界各国在控制MSM群体HIV/艾滋过程中面临着与中国类似的挑战。在美国，不同种族在享受医疗、接受治疗和对性伴侣状况了解的程度存在差别，这是不同种族HIV感染率不同的主要因素。和中国类似，在许多拉美和非洲国家，对感染HIV的恐惧成为HIV/艾滋和同性恋群体接受检测与治疗的主要障碍。

 


虽然上面几条建议在微观的层面可望取得成效，但只有通过政策、宣传、研究和治疗方面进行大规模的综合力量，才能显著降低新感染者的人数。HIV-1/艾滋带来的挑战并非不可战胜，但需要我们及时有效地行动起来。

PERSPECTIVES past. Hence, the proposal does not address the past and only deals with 'from this day forward'.
Of course, detailed implementation of such a scheme needs to be worked out. But I leave it to Chinese researchers who are much more familiar with tradition and customs to determine. And for readers who agree with this proposal, you are urged to support it by writing to the Chinese Academies or this journal.

MSM and HIV-1 infection in China
Hong Shang 1, * and Linqi Zhang 2, * 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.

ALARMING STATISTICS
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][3][4][5][6]. According to statistics from the Chinese Ministry of Health and UNAIDS [7]  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][9][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]. 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 exchangedmoney 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.

INCREASING VIRUS COMPLEXITY
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][18][19][20][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.

UNIQUE CULTURE AND SOCIOECONOMIC FEATURES
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.

CHALLENGES AND OPPORTUNITIES
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 nongovernment 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][24][25][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 microscale, 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.