China and HIV Vaccine Research: An Old Country with a New Commitment

China and HIV Vaccine Research: An Old Country with a New Commitment Yunda Huang1*, Steven G. Self1,2 and Yiming Shao3 1Statistical Center for HIV/AIDS Prevention and Research, Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, USA 2Department of Biostatistics, University of Washington, Seattle, USA 3National Center for AIDS/STD Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China


HIV/AIDS in China
Since its first AIDS case was identified in 1985, China's HIV/AIDS epidemic has expanded in size and spread in regions throughout the country. By 2002, HIV-positive people were present in all Chinese mainland provinces, municipalities, and autonomous regions [4]. In 2008, AIDS became China's number one killer infectious disease [5]. Joint research by the Health Ministry of China and WHO estimated total HIV infection cases of 0.74 million, with more than 0.13 million AIDS cases in China in 2010 [6]. In 2011, more than 48,000 new HIV infections were reported, and mortality from AIDS was almost 30,000 [7]. Although China's HIV epidemic remains at low prevalence overall (0.1% among adults) given its large population size, considerable concerns have been raised to the public and government officials regarding pockets of high infection rates among several sub-populations including Former Plasma Donors (FPD), Injecting Drug Users (IDU), Men who have Sex with Men (MSM), and most recently discordant heterosexual couples (DHC). HIV transmission in FPDs was greatly reduced after the banning of unregulated commercial blood collection in 1996 [8,9]. However, in IDU populations, HIV prevalence of more than 20% was reported in cities along or close to the drug trafficking road in the Province of Yunnan, Xinjiang, Sichuan, Guizhou, Hunan and Guangxi in 2004 [7]. A cohort study conducted between 2002-2005 reported an HIV incidence rate of 2.3 per 100 person-years in a drug trafficking city in southwest China [10]. In MSM populations, HIV transmission through homosexual sex accounts for 42% of new infectionsin 2009 [11] with an alarmingly high incidence rate of 5-8 per 100 person-years in some regions of China such as Shenyang [12] and Beijing [13]. The epidemic continues to spread further into the general population mostly through heterosexual transmission. In 2009 around 42 percent of people newly infected with HIV became infected through heterosexual sex [11]. A meta-analysis of heterosexual transmission among HIV discordant couples in China estimated an HIV sero conversion rate of 1.2 (95% CI: 0.9-1.7) per 100 person-year with an overall prevalence estimate of 11.5% (95% CI: 8.2% -15/2%) for HIV prevalence through heterosexual transmission in discordant couples [14].
These statistics have resulted in enormous pressure on the Chinese government to carry out effective prevention and imperative control of the HIV/AIDS epidemic in China. In the 1950's, the newly established People's Republic also faced serious public health challenges when 10% of national minorities, 5% of Chinese city dwellers and 2-3% of Chinese rural residents had syphilis, and the majority of sex workers living in urban areas had one or more Sexually Transmitted Diseases (STDs) [15,16]. The Chinese government was able to achieve virtual eradication of sexually transmitted diseases by massive health campaigns that were mostlyportrayed as patriotic [17]. However, today the value of freedom, personal wealth and happiness, as influenced by western culture since China reopened its doors to the west in the 1980's, often dominates the public's patriotic emotions towards government's campaigns. The government also realized that propaganda of drastic measures that worked before is no longer as effective to solve public health problems in China [18,19]. As a result, more science-based strategies have been implemented in China. For example, reduction of HIV transmission has been observed among the IDU populations due to the government's few strategies including the implementation of needle exchange programs since 1999 [20,21] and Methadone maintenance treatment programssince 2004 [22,23]. However, effective interventions among other high risk groups have been difficult to reach high coverage primarily due to their massiveness and underground nature. Discordant heterosexual couples are partially hidden and hard to reach because they are mainly comprised of migrant workers, their families, under-ground sex workers and their clients, and, covert gay men and their wives. Although homosexuality is becoming more tolerated in the cities, MSMs are often in a heterosexual marriage to conceal their true sexual orientation due to high levels of stigma toward homosexual sex in the Asian culture.

HIV Vaccine Research in China
More recently, the Chinese government realized the development of a safe and effective HIV vaccine could provide the best hope to control the HIV/AIDS epidemic, particularly among those hard to-reach risk groups and in resource-constrained regions. Such a commitment was highlighted during a visit to China CDC by Chinese Premier Wen Jiabao on the World AIDS Day in 2011, when he stressed on the importance of HIV vaccine research [24]. Such a strong political commitment in China often translates into important financial support.   [35]. China's self-developed HIV vaccine candidate, DNA + rTV, has been proven to be safe and immunogenic in Phase Ia and Ib clinical trials [36,37]. Given that the vast majority of HIV vaccine resources are currently devoted to development and testing of non-replicating vector vaccines [38], findings from such a trial is expected to be of high interest to the HIV vaccine research community worldwide.
In addition, with dominant HIV circulating strains of CRF01_AE, CRF07_B'C, and subtype B [39], China is in a unique bridging position to translate findings in China to other regions of the world that share common HIV subtypes in the circulating strains, including Latin America, North America, the Caribbean and Western Europe. Given its massive population and often centralized and well-equipped clinical sites and laboratory facilities, China is also in a unique position to speed up the evaluation of HIV vaccine candidates with strong commitment from its government. While there may be a greater need of transparency and openness from the Chinese government and scientists to collaborate with international stakeholders, there is also a need for foreign governments and organizations to better understand the cultural and societal background in China's research community. For example, historically dominated by a largely shame-based Confucian culture in which "… men hesitated to speak, for if their conduct fall short of what is said, it would be shameful. " (Analects of Confucius 4: 22), China is still "culturally-inclined" to cautiously share "uncertain" information with outsiders. This caution, however, should not be confused with an unwillingness to collaborate. Investment in a collaborative relationship of mutual trust and understanding with clear and common research goals can result in an openness of information sharing sufficient to support the collaboration. Another challenge is that China, being more frequently in the spotlight for economic growth and human rights, has a strong desire to make impact on its own effort. Although not unique to China, this certainly requires nuance and sensitivity in handling international collaboration with China. Last but not least, relatively tight regulatory requirements on early phase human clinical trials may also place constraints on the development of a successful HIV vaccine in China.
Nevertheless, China is a large and open country that possesses sufficient social and political motivations, as well as financial resources and scientific capability to play an important and unique role in the global search for an effective vaccine against HIV. Although the discovery of a successful HIV vaccine may seem elusive after three decades of concerted effort, the HIV vaccine field must not despair especially given the development of a successful vaccine had typically required decades to accomplish. China is now poised to fully engage its considerable resources in this effort and take its place among the global leaders in the search for a safe and effective HIV vaccine. This could not come at a better time.