Current human immunodeficiency virus epidemic and its response in China

KANG Lai-Yi

Shanghai Municipal Center for Disease Control and Prevention, Shanghai 200336, China

There is no doubt that human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) is a transmissible disease in China[1]. The first patient with AIDS was identified in 1985; since then, as of October 31, 2010, a total accumulative number of 370 000 patients with HIV/AIDS have been reported. Of them, there were 130 000 patients living with AIDS and 80 000 deaths, respectively. The Ministry of Health of China working together with the Joint United Nations Programme on HIV/AIDS (UNAIDS), World Health Organization (WHO), and relevant International Organizations made an estimation for the AIDS epidemic in 2009 of China and suggested that the estimated number of people living with HIV (PLHIV) in China was 740 000 (ranging from 560 000 to 920 000) and the prevalence rate in the population was 0.057% (0.042%-0.071%)[2]. Although the disease has been spreading for more than 25 years, China is still at a low-HIV prevalence rate. However, the Chinese government is aware that with any slight increase in the rate, the absolute infection number would be markedly increased due to China’s large population. In fact, the epidemic has already spread more widely from high-risk groups to the general population, especially in the high prevalence areas[2,3].

1 Current trends of the HIV epidemic in China

1.1 Regional differential in distribution

Although the disease has spread to all 31 provinces in the mainland of China since 1998, the accumulative number of PLHIV in Yunnan, Henan, Guangxi, Xinjiang, Guangdong, and Sichuan accounted for 80.5% of the total reported HIV/AIDS cases. In most of these provinces, there were 55 counties where the number of HIV-1-infected persons exceeded 1 000 in 2009, while only 43 counties reported PLHIV in 2008[4-7].

1.2 Predominance of sexual transmission

Sexual transmission continues to be the predominant mode of transmission. HIV spreads more frequently among men who have sex with men (MSM). 44.3% and 14.7% were infected through heterosexual transmission and homosexual transmission, respectively, among cumulative infected people; based on new infections estimated in 2009, heterosexual transmission accounted for 44.2% while homosexual transmission rose to 32.5%[8-15].

1.3 National low-level prevalence and locally serious epidemics

Although China had a low-level prevalence in 2009 with 0.057% estimated cases, Yunnan, Guanxi, Henan, Sichuan, Xinjiang, Guandong, etc., remained at a steady, high level of reported cases. Typical examples of high-level prevalence rate areas include the Dehong and Honghe counties in Yunan Province and Yining and Wulumuqi cities in Xinjiang Uighur Autonomous Region, particularly since 2007. As surveyed in recent years, the reported numbers from some areas have increased quickly in Sichuan and Guanxi Provinces[2].

1.4 Variety of HIV/AIDS epidemic patterns

Recently, epidemic patterns have varied. HIV-1-infected individuals have been found among individuals <15 years old and >50 years old, with an obvious annual increase. The reported cases among students (especially among those attending universities) increased quickly. In addition, an increasing number of transnational and transprovincial marriages have resulted in “cross-infection” by the different strains, which may result in the formation and spreading of HIV-1 recombinant strains in these areas[3-5].

2 HIV-1 subtype diversity

Two nationwide HIV molecular epidemiological surveys have been conducted in China[5,16]. The first one was conducted in the 1990s (1996-1998) and showed that the HIV-1 subtype B’ was predominant (47%); CRF_BC was next (30%). However, the findings from a second survey conducted from 2001-2003 showed that the distribution of HIV-1 subtypes had changed and subtype diversity had occurred, revealing a distinctively geographic distribution of subtypes in China with diverse subtypes circulating throughout China. Subtype B’ (Thailand B) is the predominant strain in the central part of China (Henan, Hubei, Anhui, Shanxi, etc.), CRF07_BC is predominant in northwest (Xinjiang) and southwest (Chongqing). CRF08_BC is predominant in southeast/south (Guangxi, Yunnan, etc.), while CRF01_AE is predominant in coastline provinces, such as Shanghai, Zhejiang, Jiangsu and Shandong, with the exception of Guangxi and Yunnan. With the spread of HIV-1 through sexual contact (including MSM), CRF01_AE is spreading throughout most of China’s provinces. In 2001-2003, at least 6 subtypes, including B’, B, A, C, CRF07/08 and CRF01_AE could be identified in China. Of them, 50% of the subtypes were CRF_BC; with the addition of CFR_AE (15%), nearly two thirds of the circulating subtypes were recombinant. An analysis of subtypes by transmission mode showed that except for the fact that blood donor subtypes were identified mostly as B’, the results from two surveys were quite different. For example, among drug users before 2000, 91% were infected with B’ and / (or) C strains, while in the 21st Century, 81% and 18% were infected with CRF07/08_BC and CRF01_AE strains, respectively. Subtype B’ and C strains were rarely seen. Sexual transmission is now a leading cause of spreading different subtypes in China. From the survey conducted in the 1990s, CRF01_AE (67%) was detected mainly in persons identified as contracting the disease via sexual contact, while based on the survey conducted in the 2000s, subtypes were identified as CRF07/08_BC (30%), CRF01_AE (27%), B’ (25%), and C, A, CRF02_AG (16%). Although a national-level survey has not been conducted in recent years, several provinces have independently conducted an investigation into the prevalence of HIV-1 genetic subtypes. Actually, diverse HIV-1 subtypes have been found in different provinces over the past years. Mostly HIV-1 clades and some unique recombination form (URF) strains have so far been identified in China[17-24].

3 Emergence of HIV drug resistance

As is well known, development and transmission of HIV drug resistance (HIVDR) has become a barrier against the use and promotion of highly active antiretroviral therapy (HAART), and therefore has become a public concern. However, the occurrence of HIVDR is inevitable because of the high degree of HIV replication and mutation that occurs under antiretroviral drug therapy particularly because this therapy is needed during the patient’s lifespan[25]. HIVDR includes primary drug resistance (transmission of HIV drug resistance, TDR) and secondary drug resistance (occurrence after antiretroviral therapy). China belongs to one of the resource-limit countries. Surveillance of TDR is an essential public health component of a comprehensive HIV strategy. Since 2004, according to WHO recommendation, China has conducted several surveillance efforts[26]. In addition to periodical HIVDR retrospective and perspective surveys among treatment-naïve and antiretroviral-treated patients, key surveys include HIVDR early warning indicators, HIVDR sentinel surveillance, and HIVDR threshold survey. At present, although the rate for TDR has been increased in the last decade, it’s still relatively low in China. For example, the TDR rate was 2.9% in 2004, 4.4% in 2005, and 3.6% in 2009, which was still lower compared with other countries[27,28]. On the other hand, a randomized investigation of HIVDR among patients on HAART has been carried out annually in certain provinces, i.e., 14 provinces in 2004, 31 provinces in 2005, 28 provinces in 2006-2007, and 10 provinces in 2009-2010. There was an obvious difference in HIVDR rate for different medication protocols for first-line therapies. The rate for HIVDR using azidothymidine (AZT)/didanosine (DDI)/nevirapine (NVP) and stavudine (d4T)/DDI/NVP was approximately 25.7%, while the HIVDR rate using modified first-line protocols [AZT/lamivudine (3TC)/NVP, d4T/3TC/NVP or AZT/3TC/efavirenz (EFV) and D4T/3TC/EFV] was only 1.6%-9.1%. Unfortunately, the updated rate for HIV mutation among patients taking first-line antiretroviral therapy in some areas was up to 30%; this provided the rationale for the use of second-line antiretroviral therapy. Comparison of HIVDR rates in three major antiretroviral groups revealed that higher HIVDR rates were associated with non-nucleoside reverse transcriptase inhibitors (NNRTIs) and with nucleoside reverse transcriptase inhibitors (NRTIs), while HIVDR rates associated with protease inhibitors were lower. The average rate for HIV-1 drug resistance was 9.5% throughout China from 2009-2010, which was much lower than the rate of 17.8% within the period of 2006-2007 when 3TC was being prescribed instead of DDI as first-line therapy. The most frequent NRTI or NNRTI-related mutations were M184V/I and K103N/R, respectively. Within the period of 2008-2009, a nationwide survey focusing on HIV infection among MSM from 61 cities was conducted and it revealed that the average rate for HIV infection in this population was 5%, with some being more than 10%. 363 HIV strains from MSM living in 15 provinces were detected and the average HIVDR rate was 6.1% (including >10% in 3 provinces). It is noteworthy that the primary HIVDR rate was much higher than other populations (<5%). The most frequent mutation codon detected in HIV-1-infected MSM was V118I[29-32]. It should be pointed out that although from 2004 to now the strategy for HIVDR surveillance and monitoring has been conducted for purposes of public health surveillance in China, since 2010 the Ministry of Health has required genotyping detection for one tenth of antiretroviral-treated individuals in order to understand if the clinical failure has occurred due to drug resistance using first-line therapy and to determine if it is necessary to use second-line antiretroviral therapy instead of the first-line therapy. The integration of HIVDR public health surveillance and individual clinical HIVDR testing is a new attempt in China[33,34].

4 China’s response to HIV/AIDS

4.1 Strengthening governmental leadership

The almost 30-year epidemic history of HIV has confirmed that HIV/AIDS prevention and control efforts throughout the world depend on governmental awareness and promise[4]. Since the severe acute respiratory syndrome (SARS) epidemic of 2003, the Chinese government has strengthened leadership at different levels[5-7]. They participated in many AIDS activities, especially during World AIDS Days to meet patients infected with HIV/AIDS and their families, their orphans, and front-line medical staff and social workers; they were called into expert workshops; and they supervised the next phase of AIDS prevention and control strategies. The central government, all 31 provincial governments, and most of the local level governments (including different departments) have set up AIDS Working Committees to form AIDS response leadership bodies, to put AIDS issues in the official agenda; to enhance departments’ and non-government organizations’ roles in AIDS prevention and control; to increase financial investments from both central and provincial governments. The central government has increased investments from 940 million RMB in 2007 to 1.22 billion RMB in 2009 and has stipulated relevant laws, regulations, and policies, including efforts to protect the rights of PLHIVs. Particularly, the Regulation on AIDS Prevention and Control, the creative policy to ensure AIDS prevention, treatment and anti-stigma and to create a positive environment for the removal of discrimination have been established[35-40].

4.2 Conducting measures for AIDS prevention and control

4.2.1EnhancinghealtheducationThe health education and health promotion related to AIDS have been carried out to enhance the public’s awareness, and to promote self-protection, anti-stigma, and anti-discrimination[4,41-43].

4.2.2EstablishingprofessionalorganizationsThe central, provincial and local county Centers for Disease Control and Prevention (CDC) system has been set up nationwidely and a special branch has been established to take measures to prevent and control AIDS. Designated hospitals and maternal-infant institutions have been serviced for AIDS medical care and an HIV lab network has been established for diagnosis, monitoring, evaluation, research, and technical support[4]. Nationwidely, there have been three different functional HIV lab networks, which have developed gradually from the 1990s to present. Particularly, a network of HIV serological labs has been established; 8 306 HIV screening labs and 318 HIV confirmatory labs were set up by the end of 2009. Since 1995, the China CDC and all 31 provincial CDCs have developed HIV network labs for molecular epidemiology surveillance and the HIVDR surveillance and monitoring network labs were developed in 2004[44-46]. At first, 4 state key labs were established, which were located within the China CDC, the First Affiliated Hospital of China Medical University, Department of AIDS/Sexually Transmitted Disease (STD) Control and Prevention of Shanghai Municipal CDC, and the AIDS Research Department of the Academy of Military Medical Science. The first three key labs have been accredited as national HIVDR network labs by WHO, and approximately 10 local HIVDR labs in provincial CDCs and relevant hospitals were set up or being developed[25].

4.2.3PromotingcomprehensiveinitiativesforpreventionandcontrolSince the 1990s, the national sentinel surveillance and testing system has been established. For example, in 2009, there were 1 318 sentinel surveillance sites, including 14 selected groups and 465 295 persons surveyed[5]. As a result, the rate for positive HIV antibody was 1.6%. An average HIV-positive rate within various risk populations was observed: drug users 5.6%, injection drug users (IDUs) 8.0%, female sex workers (FSWs) 0.4% and MSMs 5.2%. In 2009, there were 7 335 clinics to provide Voluntary Counseling Testing (VCT) and 1 630 926 received counseling; of them, 1 605 079 were being tested for HIV antibody. Management of blood donations and clinical use of blood have been strengthened[44]. For example, in 2009 a total of 3 654 tons blood were voluntarily donated; all donors received HIV testing; quality control systems (internal and external) were set up at all blood stations and labs; and standardized operating procedures were followed. Comprehensive interventions among high-risk groups (including MSMs, FSWs, PLHIVs) have been conducted to reduce HIV/STI transmission and to reduce the spread of HIV to the general population. Based on sentinel surveillance data from 2009, condom use rates calculated from last intercourse were up to 85.1% among sex workers and 73.1% among MSMs. Many areas have established special intervention teams to implement high-risk reduction strategies to the above groups. In 2009, there were 680 Methadone Maintenance Treatment Clinics in China; 241 975 IDUs were being treated and an estimated reduction of 3 000 cases with newly acquired HIV infection and reduction of heroin expense of 22.4 tons were observed. Interruption of HIV maternal-infant transmission is efficiently achieved. In 2009, more than 1 400 000 pregnant women were screened for HIV throughout several provinces with higher HIV prevalence rates; the rate for interruption of HIV maternal-infant transmission using antiretroviral medication was 75.3%[45-47].

4.2.4FreeAIDStreatmentprogramsThis is one of the national policies, titled “Four Free, One Care”. It was created to enhance the quality of life and to reduce mortality of patients living with AIDS. By the end of 2009, 79 946 adult patients with AIDS and 1 793 children with AIDS received free antiretroviral therapy, all of whom lived in 1 281 counties of all 31 provinces. In addition, 2 155 patients with AIDS started to receive second-line antiretroviral treatment. It was evident that the survival rate increased after antiretroviral treatment and the rate after 12 months of treatment was an average of 83.6% in 2009. Case mortality rates for adults with AIDS were 28/100 person-year and 5/100 person-year before and after antiretroviral treatment, respectively[5,48-52].

4.2.5HeighteningscientificresearchprojectsandcollaborationsIn order to enhance HIV prevention and control program quality, to reduce the incidence rate of new infections, and to create new technology, the Chinese government has put much more attention on scientific and technological research. Over the past two years, a total of 316 180 000 RMB were funded to national mega research programs focusing on novel HIV diagnostic reagents, epidemic patterns, antiretroviral treatment, HIVDR surveillance, immune protection mechanisms, biological prevention interventions, vaccine development, HIV and research onMycobacteriumtuberculosis(MTB)/hepatitis B virus (HBV)/ hepatitis C virus (HCV) co-infections, etc[5,53]. In the meantime, international and domestic collaborations have become key ways to acquire knowledge and experience in the HIV/AIDS field through the Global Foundation, China-US, China-Canada projects, etc, to promote effective work on AIDS control[41].

In conclusion, due to the above efforts, the rising trend of the HIV epidemic is slowed, demonstrating the great impact of the comprehensive prevention and control of HIV/AIDS. It was also evident that new infections are decreasing every year, i.e., annual new HIV infections decreased from 70 000 in 2005 to 50 000 in 2007 and 48 000 in 2009.

5 Facing challenges and further actions

Although the HIV epidemic in China has diminished, the Chinese people are now facing different challenges[49,54,55]: (1) Lack of AIDS knowledge among the public, even among medical staff. A recent investigation of average knowledge rate for HIV transmission and prevention ranged from 32.8% to 40.3%. (2) Wide existence of HIV epidemic factors, including MSM displaying multiple sex behaviors and low rate for persistent condom use; IDUs with a certain rate for sharing needle and syringes and increasing use of new drugs; FSWs unable to persist on condom use and being at risk for STI; and in particular, difficulty in spreading such information among these populations. (3) High population movement. Annual migrants for the whole country up to 220 millions from countryside to cities. (4) More than half of the estimated patients living with HIV/AIDS have yet to be identified and finding newly infected individuals is difficult. (5) Stigma and discrimination in the society. (6) Unbalanced implementation of “Four Free, One Care” in different areas and emergent increases in HIVDR. (7) Heavy responsibility for the development of HIV vaccine, curable anti-HIV drugs and new diagnostic method development. (8) Weak monitoring and evaluation systems. (9) Some local leaderships still lack of awareness and promise. (10) Lacking professional personnel and teams.

How to deal with the above challenges?

The government should continue to strengthen leadership, further carry out the responsibilities, with particular focus on some geographical areas with higher HIV prevalence and migrant populations, and further conduct a range of HIV prevention and control measures and relevant policies (including monitoring and inspecting)[56]. In the meantime, a series of comprehensive works should be conducted, including expanding coverage of health education, health promotion, surveillance and testing, preventing maternal-infant transmission, carrying out structure intervention (both behavioral and bio-interventional), strengthening blood safe management, controlling nosocomial infection, and providing care and support for HIV-infected and vulnerable groups. It is also very important to create a sound social environment for AIDS control, such as persisting on anti-stigma and anti-discrimination for patients with HIV/AIDS, protecting their rights for medical care, schooling, jobs, and strengthening treatment programs for criminals with HIV/AIDS; enhancing professionals’ capacity to build AIDS prevention and control and stimulating research and scientific achievements[57,58]. We are confident that with the above actions, China can continue to maintain a low incidence of HIV/AIDS.

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