Pharmacotherapy

Monday, March 14, 2005

Opioid substitution and HIV/AIDS treatment and prevention

Thomas Kerr, Alex Wodak, Richard Elliott, Julio S Montaner, Evan Wood

The Lancet, Vol 364
November 27, 2004

The HIV/AIDS epidemic remains a global crisis affecting millions of lives as well as the development of many countries throughout the world. About 40 million people are infected with HIV, with an estimated 5 million people infected during 2003 (1). In many of the regions with the fastest growing HIV epidemics, such as parts of Asia, eastern Europe, and the former Soviet Union, injection drug users (IDUs) and their sexual contacts account for most new infections. Opioid dependence is the underlying condition fuelling the HIV epidemic in many countries.

The development of new antiretroviral treatments improved the care of HIV-infected persons (2), although the anticipated benefits have been eroded by poor access to in areas hardest hit by the epidemic (3). While access has been particularly poor in those areas of southern Africa where HIV prevalence is highest, in many regions with large IDU-driven HIV epidemics, access to antiretrovirals is also exceedingly low (4).

In recent years several large international initiatives have attempted to increase access to antiretroviral treatments. Most notable are the 3 by 5 initiative of WHO and UNAIDS, which aims to provide treatment to 3 million people in developing countries by the end of 2005 (5), and the Global Fund to Fight AIDS, Tuberculosis and Malaria (GFATM), which provides millions of dollars each year for the prevention and treatment of HIV in lower income countries (6).

Although regions with IDU-driven epidemics are expected to be targeted by both 3 by 5 and GFATM, the successful implementation of antiretroviral treatment in these settings is impeded by significant problems resulting from untreated opioid dependence. Attracting and retaining IDUs into HIV/AIDS care if antiretroviral treatments are provided without adequate addiction treatment has proved problematic (7, 8).

Clinical studies show that providing drug-dependence treatment services generally greatly enhances uptake, adherence to, and retention in HIV treatment in IDUs (8). One of the most well-evaluated strategies has been the provision of opioid-substitution therapies, such as methadone and buprenorphine, which reduce HIV risk behaviour, overdose deaths, and also improve outcomes from antiretroviral treatment in HIV-infected opioid users (7-13). With many controlled clinical trials (12), the weight of evidence behind these modalities is so strong that substitution therapy has now been recognised as the most effective treatment for opioid dependence (14), and has recently become the cornerstone of treatment in many parts of the world (15). Unfortunately, despite being relatively inexpensive and uncomplicated therapies, methadone and buprenorphine are often not offered, provided in a suboptimal fashion, or banned in many of the countries where injection-related HIV epidemics are currently raging (6, 15).

In light of the challenges in delivering HIV/AIDS care to IDUs (3), WHO has recommended the integration of opioid-substitution therapies in its HIV treatment guidelines for IDUs in resource-limited settings.4 However, methadone and buprenorphine are not presently included in WHO’s Model List of Essential Medicines (16). There are several adverse consequences associated with the status of opioid-substitution therapies in relation to the list as WHO and others work to increase access to antiretroviral treatments and improve the health of IDUs around the world. The primary objectives of WHO’s Drugs Action Programme is to reduce morbidity and mortality by helping countries integrate essential drugs and medicines into their national health system (17). Therefore, the addition of these drugs to the essential medicines list would facilitate greater access to substitution therapies and greater integration of these therapies within the HIV care systems in countries where access is currently limited. Adding these drugs will also remove barriers to securing funding for integrated treatment systems that couple opioid-substitution therapy with HIV treatment because many funding agencies, including GFATM, require justification for the purchase of drugs not currently on the list. Finally, recognition of the overwhelming scientific support for opioid-substitution therapy (7, 12, 23), by the addition of these medications to the essential medicines list, will send a clear message to nations confronted by IDU-driven HIV epidemics that these drugs are regarded as essential components of HIV prevention and treatment for IDUs.

In March, 2005, there will be an opportunity to address these concerns when WHO’s Expert Committee on the Use of Essential Drugs will consider applications requesting that methadone and buprenorphine be added as essential medicines. Essential drugs are selected on the basis of public-health relevance, safety, efficacy, and cost effectiveness, and a large volume of clinical evidence indicates clearly that methadone and buprenorphine satisfy these criteria (7, 12, 13, 18, 19). Given what is now known about the effectiveness of opioid-substitution therapy in HIV prevention and treatment (7, 12, 13), a decision to add these drugs to the list is needed to help ensure greater access to substitution therapies and antiretroviral treatments, and in turn to help to bring the HIV/AIDS epidemic among IDUs under control.

Authors:

Thomas Kerr, Alex Wodak, Richard Elliott, Julio S Montaner, Evan Wood

British Columbia Centre for Excellence in HIV/AIDS, St Paul’s Hospital, Vancouver, British Columbia, Canada V6Z 1Y6 (TK, JSM, EW); Canadian HIV/AIDS Legal Network, Montreal, Quebec (TK, RE); Alcohol and Drug Service, St Vincent’s Hospital, Sydney, New South Wales, Australia (AW); and Department of Medicine, University of British Columbia, British Columbia, Canada (JSM, EW) tkerr@cfenet.ubc.ca

References:

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  2. Mocroft A, Vella S, Benfield TL, for the EuroSIDA Study Group. Changing patterns of mortality across Europe in patients infected with HIV-1. Lancet 1998; 352:1725-30.
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  12. National Consensus Development Panel on Effective Medical Treatment of Opiate Addiction. Effective medical treatment of opiate addiction. JAMA 1998; 280: 1936–43.
  13. Johnson RE, Chutuape MA, Strain EC, Walsh SL, Stitzer ML, Bigelow GE. A comparison of levomethadyl acetate, buprenorphine, and methadone for opioid dependence. N Engl J Med 2000; 343: 1290–97.
  14. WHO United Nations Office of Drug and Crime, UNAIDS. Substitution maintenance therapy in the management of opioid dependence and HIV/AIDS prevention: position paper. Geneva: WHO, 2004.
  15. Ball AL, Rana S, Dehne KL. HIV prevention among injecting drug users: responses in developing and transitional countries. Public Health Rep 1998; 113 (suppl 1): 170–81.
  16. World Health Organization. Essential medicines: WHO model list, 13th edn. Geneva: WHO, April, 2003.
  17. World Health Organization. Essential drug policies and programmes. Geneva: WHO, 2004.
  18. Ball J, Ross A. The effectiveness of methadone maintenance treatment: patients, programs, services and outcomes. New York: Springer-Verlag, 1991.
  19. Bell J, Zador D. A risk-benefit analysis of methadone maintenance treatment. Drug Safety 2000; 22: 179–90.

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