Antiretroviral Therapy for Former Plasma Donors in

E D I T O R I A L C O M M E N TA R Y

Antiretroviral Therapy for Former Plasma Donors in China: Saving Lives When HIV Prevention Fails Han-Zhu Qian1,2,4 and Sten H. Vermund1,3,4 1 Institute for Global Health, 2Vanderbilt Epidemiology Center, and Departments of 3Pediatrics and 4Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee

(See the article by Zhang et al. on pages 825–33)

Received 16 May 2008; accepted 19 May 2008; electronically published 8 August 2008. Reprints or correspondence: Dr. Sten H. Vermund, Vanderbilt Institute for Global Health, 2525 West End Ave., Ste. 750, Nashville, TN 37203–1738 (sten.vermund @vanderbilt.edu). Clinical Infectious Diseases 2008; 47:834–6 2008 by the Infectious Diseases Society of America. All rights reserved. 1058-4838/2008/4706-0017$15.00 DOI: 10.1086/590940

dices was an extraordinary public health and primary care achievement [3]. China began to move away from central planning toward a market economy in 1979. China’s agricultural reform substituted a “Household Responsibility System” in place of the deteriorating 3-tiered medical system and the almost defunct Cooperative Medical System [1]. Chinese persons living in rural areas have seen many changes. “Barefoot doctors” funded by the communes used to provide basic primary care, but they have been replaced by small health-related entrepreneurs, including fee-for-service medicine. Government services, such as hospitals, now charge far higher fees for their services than before. A new emphasis is placed on the training and placement of “village doctors,” who have ∼3 years of primary care training and who charge for their services. The public health system has also changed. Modern China relies less on community mobilization for public health achievement, which was the case with the successful campaigns devoted to such problems as malaria and schistosomiasis during past decades. In place of these commune-based volunteer programs, government public health programs now seek to involve community-based organizations, typically not as volunteers but as paid partners. In this context, illegal commercial blood collection activities emerged in poorer rural communities in the late 1980s and early

834 • CID 2008:47 (15 September) • EDITORIAL COMMENTARY

1990s, often abetted by corrupt local leaders or health officials. Voluntary blood donation does not meet the demands of the medical system in China. Blood is seen as a vital fluid in Chinese society. Donations are typically made in 200–250 mL volumes, rather than the 450–500 mL volumes obtained in American or European donations. In China, fewer people donate blood and they donate in lower volumes than in many other nations. In this environment, unscrupulous businessmen offered money for blood in illegal mobile rural blood donation schemes. These businessmen used plasmaphoresis to harvest plasma and reinfuse pooled RBCs of the same blood type, such that persons could donate again in a short time (typically within 1–4 weeks) without becoming anemic. Thus, farmers and their spouses donated blood repeatedly in short periods of time to supplement their very low incomes, until the itinerant blood procurers moved elsewhere. Mixing blood for reinfusion guarantees the transmission of bloodborne pathogens, of course, given that a single infected donor can infect dozens of other donors. The consequent epidemics of HIV and hepatitis C virus are well documented [4– 8]. The spread of hepatitis B in this environment has been less well studied, but 1 study suggested that it may not have been spread as extensively, for unknown reasons [4]. Chinese officials suppressed this destructive and illegal business in the

Downloaded from http://cid.oxfordjournals.org/ by guest on January 12, 2016

The spread of HIV and other bloodborne infections in rural communities in eastcentral China in the late 1980s and early 1990s was a tragic public health event. This occurred at a time of great transition. A market-oriented economy was emerging across the country, and the communebased rural health care system was collapsing. From the 1950s through the 1970s, China had established a 3-tiered health care infrastructure, including village barefoot doctors, township health care centers and county hospitals, and a low-cost Cooperative Medical System that provided basic health insurance [1]. This primary care infrastructure and basic insurance scheme served rural residents efficiently during a time that 180% of all Chinese persons lived in rural areas (compared with 50%–60% in 2008). The infant mortality rate decreased from ∼200 of 1000 live births in 1949 to 47 of 1000 live births in 1975, and life expectancy increased from 35 years in 1949 to 65 years in 1975 [2]. China’s gross national income per capita in 1975 was only $230, suggesting that the improvement in health in-

[11–12]. The policy for universal access to treatment in Brazil yielded a 40%–70% reduction in mortality, a 60% reduction in morbidity, and an 85% reduction in hospitalization from 1997 to 2003 [13]. In sub-Saharan Africa, where 68% of the world’s HIV-infected adults and 90% of the infected children reside, the number of infected people with access to ART increased from 100,000 to 11,000,000 from 2003 to 2006 [14]. In settings as diverse as Haiti and Zambia, ART delivery programs are saving lives on a large scale, although to date, published data from large-scale programs are primarily from urban centers [15, 16]. China’s success in overcoming constraints in rural care infrastructures to provide life-saving care and treatment to infected persons demonstrates the feasibility of rural HIV care programs [10]. China’s AIDS epidemic and ART program have characteristics that suggest special opportunities and challenges. Chinese farmers and their spouses in the poorer former plasma-donating communities in Henan and surrounding provinces typically have low-risk lifestyles; little secondary transmission has been documented [4]. However, China is a large country, and secondary transmission is feasible in some rural venues where high-risk behaviors are prevalent [17]. Most Chinese persons living with HIV/AIDS reside in rural regions, including Xinjiang, Guangxi, and Yunnan provinces, where injection drug use is driving HIV transmission [9, 18]. An increasing proportion of new HIV/AIDS case reports in China over time are attributable to sexual transmission [9, 19]. In 2007, the number of reported cases of HIV infection attributable to sexual contact surpassed the number of cases attributable to the previously dominant route of infection—injection drug use—for the first time. Many female sex workers and men who have sex with men may become infected with HIV in cities and later serve as an epidemiological “bridge” to their rural home regions of origin. This is exactly what occurred in the southeastern United

States; an early wave of rural cases reflected residents returning home from urban areas after becoming infected, but later cases were autochthonous [20, 21]. Illegal drug users, sex workers, and men who have sex with men face challenges of stigma and fear of arrest in China, which inhibits their pursuit of counseling and testing, prevention, and health care services. Although the need to provide care and treatment in central China, where former plasma donors reside, is obvious and urgent, there are many other rural areas where sexual and drug injection risks continue to be factors and prevention programs are inadequate. More and more infected former plasma donors will develop symptomatic AIDS in the next few years, and those currently receiving ART will live longer than previously untreated patients; the demand for care will increase. Few rural residents now have health insurance. The Chinese government has made rural health care reform a top priority. The New Cooperative Medical Scheme, a government-run voluntary insurance program, was initiated to insure rural residents against catastrophic health expenses and to protect them from impoverishment by illness [22]. The annual premium is 50 yuan (∼$7); the central and local governments pay 20 yuan each per person, and the farmers pay 10 yuan per person. Fifty yuan represents one-third of a farmer’s estimated health spending in the poorer central and western provinces of China [22]. So far, this new scheme has not taken HIV/ AIDS into consideration; the limited pool of insurance-derived funding in communities with a large number of patients with AIDS would deplete the reserves of the New Cooperative Medical Scheme. The Chinese government will need to continue expanding the China Cares program in these areas. Monitoring drug resistance and increasing drug options for patients infected with drug-resistant viruses is necessary. A 2005 publication from Henan province indicated that 18%–62% patients who re-

EDITORIAL COMMENTARY • CID 2008:47 (15 September) • 835


early 1990s, but only after much damage was done. An estimated 57,000 former blood and plasma donors have been infected with HIV in Henan, Anhui, Hubei, and Shanxi provinces [9]. More than a decade has passed since the apex in activity of these grotesque illegal plasma collection activities. Many infected former plasma donors have advanced HIV disease and need access to health care that is beyond their economic means. To respond to this need, the Chinese government started the China Cares program in 2003, with the slogan “Four Frees and One Care.” The program offers free HIV testing, free antiretroviral treatment (ART), free services for preventing mother-to-child transmission, free schooling for those who are orphans because of AIDS, and care and economic assistance to the families of people living with HIV/ AIDS. This nationwide program gives special attention to rural communities with a large number of HIV-infected former plasma donors. In this issue of Clinical Infectious Diseases, investigators from the Chinese Center for Disease Control and Prevention and the US National Institutes of Health report the impact of the national program that provides free ART on mortality in a subset of 4093 Chinese former plasma donors [10]. A thoughtful analysis demonstrates that the hazard of mortality among those not receiving ART is 2.8-fold greater than that among persons receiving ART. The authors correctly recognize the potential bias of assessing clinical effectiveness outside the context of a clinical trial. They demonstrate that the sickest persons were most likely to receive ART, which suggests that their findings might be a conservative estimate of the benefits of ART for rural former plasma donors infected with HIV in China. That the program has reduced mortality substantially in a very rural setting is an inspiration for the global push to provide HIV care in rural areas. In the United States, millions of life-years have been saved with antiretroviral drugs since 1989

5.

6.

7.

8.

9.

10.

Acknowledgments Potential conflicts of interest. H.Z.Q. and S.H.V.: no conflicts. 11.

References 1. Liu Y, Hsiao WC, Li Q, Liu X, Ren M. Transformation of China’s rural health care financing. Soc Sci Med 1995; 41:1085–93. 2. Jowett AJ. China: population change and population control. Jowett AJ. GeoJournal 1986; 12:349–63. 3. Globalis. China: gross national income per capita. Available at: http://globalis.gvu.unu .edu/indicator_detail.cfm?IndicatorIDp140 &CountrypCN. Accessed 16 May 2008. 4. Qian HZ, Vermund SH, Kaslow RA, et al. Co-

12.

13.

14.

infection with HIV and hepatitis C virus in former plasma/blood donors: challenge for patient care in rural China. AIDS 2006; 20: 1429–35. Xu JQ, Wang JJ, Han LF, et al. Epidemiology, clinical and laboratory characteristics of currently alive HIV-1 infected former blood donors naive to antiretroviral therapy in Anhui Province, China. Chin Med J (Engl) 2006; 119: 1941–8. Zhang W, Hu D, Xi Y, Zhang M, Duan G. Spread of HIV in one village in central China with a high prevalence rate of blood-borne AIDS. Int J Infect Dis 2006; 10:475–80. Ji G, Detels R, Wu Z, Yin Y. Correlates of HIV infection among former blood/plasma donors in rural China. AIDS 2006; 20:585–91. Wu Z, Rou K, Detels R. Prevalence of HIV infection among former commercial plasma donors in rural eastern China. Health Policy Plan 2001; 16:41–6. State council AIDS working committee office, UN theme group on HIV/AIDS in China, a joint assessment of HIV/AIDS prevention, treatment and care in China. Beijing: China Ministry of Health, 2007. Zhang F, Dou Z, Yu L, et al. The effect of highly active antiretroviral therapy on mortality in HIV-infected former plasma donors in China. Clin Infect Dis 2008; 47:825–33 (in this issue). Walensky RP, Paltiel AD, Losina E, et al. The survival benefits of AIDS treatment in the United States. J Infect Dis 2006; 194:11–9. Vermund SH. Millions of life-years saved with potent antiretroviral drugs in the United States: a celebration, with challenges. J Infect Dis 2006; 194:1–5. Marins JR, Jamal LF, Chen SY, et al. Dramatic improvement in survival among adult Brazilian AIDS patients. AIDS 2003; 17:1675–82. Ojikutu B, Jack C, Ramjee G. Provision of antiretroviral therapy in South Africa: unique challenges and remaining obstacles. J Infect Dis 2007; 196(suppl 3):S523–7.

836 • CID 2008:47 (15 September) • EDITORIAL COMMENTARY

15. Severe P, Leger P, Charles M, et al. Antiretroviral therapy in a thousand patients with AIDS in Haiti. N Engl J Med 2005; 353: 2325–34. 16. Stringer JS, Zulu I, Levy J, et al. Rapid scaleup of antiretroviral therapy at primary care sites in Zambia: feasibility and early outcomes. JAMA 2006; 296:782–93. 17. Ji G, Detels R, Wu Z, Yin Y. Risk of sexual HIV transmission in a rural area of China. Int J STD AIDS 2007; 18:380–3. 18. Xiao Y, Kristensen S, Sun J, Lu L, Vermund SH. Expansion of HIV/AIDS in China: lessons from Yunnan Province. Soc Sci Med 2007; 64: 665–75. 19. Qian HZ, Vermund SH, Wang N. Risk of HIV/ AIDS in China: subpopulations of special importance. Sex Transm Infect 2005; 81:442–7. 20. Rumley RL, Shappley NC, Waivers LE, Esinhart JD. AIDS in rural eastern North Carolina-patient migration: a rural AIDS burden. AIDS 1991; 5:1373–8. 21. Agee BS, Funkhouser E, Roseman JM, Fawal H, Holmberg SD, Vermund SH. Migration patterns following HIV diagnosis among adults residing in the nonurban Deep South. AIDS Care 2006; 18(suppl 1):S51–8. 22. Yip W, Hsiao WC. The Chinese health system at a crossroads. Health Aff (Millwood) 2008; 27:460–8. 23. Li JY, Li HP, Li L, et al. Prevalence and evolution of drug resistance HIV-1 variants in Henan, China. Cell Res 2005; 15:843–9. 24. Bangsberg DR, Kroetz DL, Deeks SG. Adherence-resistance relationships to combination HIV antiretroviral therapy. Curr HIV/AIDS Rep 2007; 4:65–72. 25. Farmer P, Le´andre F, Mukherjee JS, et al. Community-based approaches to HIV treatment in resource-poor settings. Lancet 2001; 358: 404–9. 26. Wang X, Wu Z. Factors associated with adherence to antiretroviral therapy among HIV/ AIDS patients in rural China. AIDS 2007; 21(suppl 8):S149–55.


ceived treatment for 16 months had developed drug-resistant infection [23]. Improved laboratory capacity, drug procurement systems, and drug quality control systems are needed. Most importantly for drug-resistance prevention, adherence programs based on person-to-person assistance, pharmacy-based approaches, and mnemonic-help systems are vital [24–26]. Fortunately, the rural Chinese health system network is still functioning well, although it is economically inaccessible for too many people. The booming economy of the past 3 decades has accumulated wealth at both central and provincial levels. If China maintains its strong political will to help with HIV care and treatment, China’s ART-based programs can continue to expand to meet the substantial and growing need for HIV care and ART.