Chinese Medical Journal 2009;122(11):1352-1355
A public health approach to rapid scale-up of free antiretroviral treatment in China: an ounce of prevention is worth a pound of cure

Marc Bulterys,  Sten H. Vermund,  Ray Y. Chen ,  Chin-Yih Ou

Marc Bulterys (Global AIDS Program – China Office, US Centers for Disease Control and Prevention, Beijing 100600, China)

Sten H. Vermund (Institute for Global Health and Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, Tennessee, USA)

Ray Y. Chen (Global AIDS Program – China Office, US Centers for Disease Control and Prevention, Beijing 100600, China)

Chin-Yih Ou (Division of Global AIDS, National Center for HIV, Viral Hepatitis, STD, and TB Prevention, Centers for Disease Control and Prevention, Atlanta, Georgia, USA)

Correspondence to:Marc Bulterys,Global AIDS Program – China Office, US Centers for Disease Control and Prevention, Beijing 100600, China (Tel: 86-10-65329901. Fax:. E-mail:bulterys@cn.cdc. gov)
Keywords
antiretroviral therapy; China; human immunodeficiency virus; drug resistance; universal access
Abstract

China′s rapidly evolving HIV/AIDS epidemic calls for a dramatic expansion of both prevention and treatment services.1,2 Official state media recently reported that for the first time, in 2008, HIV/AIDS became China′s leading cause of death among infectious diseases.3 Estimates from the Ministry of Health indicate that around 700 000 people were living with HIV and 85 000 people had AIDS in 2007.4 Initially, HIV-1 infection was confined primarily to certain high-risk populations such as injection drug users (IDU) along drug-trafficking routes, and former plasma donors (FPD) in rural communities in east-central China.1,5-7 Now, however, HIV prevalence is increasing among female sex workers (FSW) and men who have sex with men (MSM).4,8 It is estimated that in 2008, approximately 45% of new HIV cases in China were attributed to heterosexual transmission and 12% to MSM; the proportion of women infected has also doubled in the past decade.

To respond effectively to the urgent need of patients with advanced HIV disease, the Chinese government in 2003 started the National Free Antiretroviral Treatment Program (NFATP). Initially focused on FPD in rural communities,6 this program has since expanded to all 31 provinces. In 2009, the government announced that second-line antiretroviral treatment (ART) ― at a cost of approximately $1760 per patient per year ― will be provided free to AIDS patients who have become resistant to first-line ART.9 In this issue of the Chinese Medical Journal, investigators and leaders from the National Center for AIDS/STD Control and Prevention (NCAIDS) at the Chinese Center for Disease Control and Prevention describe the formidable challenges in rolling out ART to all those who need it.10 They highlight ethical considerations in distributing the benefits of ART equitably in the context of seeking to minimize development of multi-drug resistant HIV strains. The authors conclude that the aim of universal access to ART is achievable in China with additional and innovative strategies.

In the past five years, China has made impressive progress in the development and implementation of effective HIV prevention and control programs.1,11 At the same time, the Chinese government has shown a sustained commitment to rolling out a nationwide program for free first-line antiretroviral treatment. This program has been credited with a 5-fold decrease in mortality among AIDS patients who are FPD (from 27–30 deaths per 100 person-years before 2002 to 5–6 deaths per 100 person-years in the period 2005–2006).12 An analysis of the five-year outcomes of the NFATP among 48 785 previously ART-naïve adult AIDS patients also shows low mortality (4–5 per 100 person-years) after six months on ART.13 This reduction in mortality, to levels similar to other low or middle-income countries,14-18 has been sustained among all HIV transmission risk groups. However, the analysis also showed a high rate of immunological treatment failure (using standard WHO criteria) after five years on first-line ART.13 This is of particular concern in China because of the current limited availability of more costly second-line and salvage regimens.19

The major aim of combination ART is the reduction of HIV-related mortality and morbidity by suppression of plasma HIV RNA, with a subsequent increase in CD4+ T cell count.20 Poor adherence to ART increases the risk of incomplete viral suppression, ARV drug resistance, and death.21 In a meta-analysis, once-daily ART regimens have been shown to be associated with better adherence, particularly at treatment initiation.22 HIV prevention counseling is now recognized as an important part of HIV/AIDS care (“prevention with positives”).23 Several studies have shown that being in care is associated with a strong reduction in the prevalence of sexual risk behavior.24 From a population perspective, HIV testing and early provision of ART could yield substantial public health benefits because ART greatly reduces viral load and thus transmissibility.25,26

National HIV programs should be designed to minimize the time patients spend with CD4+ cell counts less than 350 cells/µl both before and during ART.23,27 In China, the median CD4+ count at entry into treatment is 118/µl; 30% of patients in the National Free ART Program started at CD4+ less than 50/µl.13 Undoubtedly, earlier HIV diagnosis and treatment could save more lives. Routine provider-initiated testing and counseling (recommended by health care providers to persons attending certain health care services such as sexually transmitted infections or tuberculosis clinics)23 could identify many more patients before they need ART. However, a major barrier to getting patients into early care is social stigma, particularly for heroin users, sex workers, and MSM. Unfortunately, some health professionals are also not free from stigmatizing their patients.28

In the public health approach, simplified treatment protocols and decentralized service delivery enable ART delivery to large numbers of patients in resource-limited settings; and high adherence rates may alleviate the need for frequent laboratory monitoring.29 Nevertheless, some critical operational research questions pertinent to China remain. For instance, what are the optimal time and criteria to switch patients to second-line ART? How can first-line regimens be made more durable? What is the most appropriate use of viral load measurement, in addition to CD4+ cell count, in an affordable public health approach? How can new point-of-care technologies for laboratory monitoring be utilized? There is an urgent need also for health information systems to be integrated and strengthened to capture the most critical information longitudinally in order to inform public health policy.

Although HIV-infected adults in China began receiving free ART in 2003, pediatric formulations did not become available until July 2005 through support from the Clinton Foundation HIV/AIDS Initiative.30 Before this time, children were treated with adult formulations. By April 2009, at least 1400 children had received ART in China. However, the median age of children initiated on ART is 7.8 years and very few children under two years of age are currently receiving ART. Thus, services to HIV-infected children may be added to the ethical imperatives highlighted by Yin et al.10 Preventing mother- to -child transmission (PMTCT) services continue to be scaled-up in China, especially in those provinces and counties with the highest HIV prevalence, and currently cover approximately 15% of all pregnant women (out of an estimated 17.3 million births annually). Highly-active ART has become the recommended regimen for PMTCT in China since 2007.31 Rapid HIV testing of women in labor with undocumented HIV status is also common, enabling immediate provision of ARV prophylaxis.32 Early infant HIV diagnosis using PCR must also move quickly beyond pilot programs to nationwide coverage to prevent high infant mortality before diagnosis. Of course, primary prevention of HIV infection in women holds the key to PMTCT.

Yin et al10 noted key shortcomings and challenges that need to be addressed to accomplish the goal of universal HIV treatment access in China. These include earlier identification of undiagnosed patients, increased human resource capacity, and reducing stigma and discrimination, issues similar to those faced by many other national HIV treatment programs.33-36 A notable item missing from their list is the need for increased funding. The Chinese government has commendably scaled up funding necessary for the treatment of HIV/AIDS to about 800 million RMB each year in 2004 and 2005.1 Nonetheless, a key shortcoming, as noted by Yin et al,10 is the lack of sufficient human resource capacity. As patients are successfully treated and live longer, HIV/AIDS becomes a chronic disease rather than an acute disease. As such, a successful HIV/AIDS treatment program will only continue to require more and more human and financial resources. The lack of sufficient human resource capacity has been identified by a number of studies to be the most critical component preventing universal access to HIV treatment today, particularly in Africa.35,36 A second funding priority is the further expansion of drug abuse treatment services. Again, commendably, China has rapidly expanded methadone maintenance treatment programs and is doing research into the use of buprenorphine-naloxone (HIV Prevention Trials Network 058 protocol; http://www.hptn.org) for reducing drug use and HIV transmission. However, these programs need to further expand to meet national need.37 Although China does not have the magnitude of HIV infection of many other countries, the geographic spread of HIV across China increases the challenge of coordinated healthcare delivery and the human resources required.

So where does China go from here to confront and meet the challenges to achieving universal access through the NFATP described by Yin et al10? We believe that China could learn valuable lessons from successful large-scale treatment programs in several countries and from modeling studies based on African data36 to assist in future resource needs planning. Furthermore, with the wealth of data contained in the national treatment database, increased resources should be committed to continue cross-disciplinary research on how to implement best practices to optimize treatment outcomes.34 Priority questions to address include how to promote treatment accessibility for marginalized populations such as IDU, sex workers, and MSM, how to best utilize HIV drug resistance testing surveillance results to scale-up second line treatment, and how to improve treatment outcomes among HIV patients co-infected with TB and/or hepatitis B or C. Given the life-long nature of ART in the absence of a cure for HIV infection, strengthening primary care will ensure sustainability as will systems to enhance adherence with “buddies”, mnemonics, and improved social norms for HIV-infected persons.38-40

In conclusion, the Chinais Ministry of Health has demonstrated that roll-out of life-saving HIV/AIDS treatment services is feasible on a large scale, in spite of challenges.10,12 These efforts should be applauded and continually supported. We believe that a major hurdle for China (and, incidentally, the United States) will be how optimally to reform and ensure an efficient and economically accessible rural health care delivery system.41,42 There continues to be great pressure, and indeed an ethical mandate, to expand ART (including second-line) to all those in need, particularly those ostracized by society. Universal ART coverage in China will thus require substantially reduced HIV incidence in the years to come. Even with excellent HIV/AIDS programs, the sheer size of China ― home to one fifth of the world′s population ― makes universal access to HIV testing, prevention, care and treatment services an enormous challenge for the government.1,3 History has shown that China has tremendous capacity to mobilize resources quickly and develop an effective and sustainable response in the face of daunting challenges (most recently in the aftermath of the earthquake in Sichuan). We are confident that China will maintain its strong political will and continue to expand HIV prevention programs and access to high-quality care and treatment to all its people.

Disclaimer: The conclusions in this report are those of the authors and do not necessarily represent the views of the US Centers for Disease Control and Prevention or the National Institutes of Health.

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