Does buprenorphine have a role in preventing HIV transmission and treating HIV-infected IDUs? (corrected)

A review article published in the 15^th September edition of Clinical Infectious Diseases has outlined the benefits of buprenorphine (Subutex) in the treatment of intravenous drug use. The drug, which was added to the World Health Organization’s (WHO's) list of essential drugs in July 2005, may be beneficial in reducing HIV transmission through injection practices, as well as treating HIV-infected drug users.

Injection drug use is a major factor in the transmission of HIV internationally. Around 10% of all HIV transmissions can be attributed to the consequences of intravenous drug use including needle sharing or unsafe sex. Drug use has also been linked to the majority of HIV transmissions in central and Eastern Europe and Southeast Asia.

The most commonly used treatment for addiction to opioids, such as heroin and morphine, is replacement therapy with methadone. This drug mimics the effects of opioids by binding to the same receptor molecules as these drugs. These receptors, called mu-opioid receptors, are found on the surface of cells in the brain and spinal cord and trigger the drugs’ sedating, euphoric and pain-killing effects.

Methadone works by preventing the withdrawal symptoms and craving brought about when an addict stops injecting drugs. By reducing the frequency of drug injection, it has been shown to reduce the incidence of HIV infection. However, the use of methadone has a number of problems, including being itself addictive, and its risk of causing breathing problems and overdose. It also interacts with many HIV drugs.

Buprenorphine, in contrast to methadone, is a partial agonist of the mu-opioid receptor. This means that it activates mu-opioid receptors less strongly than methadone, which, the authors argue, may reduce the likelihood of it being abused, particularly in regions where it is supplied in combination with naloxone, a drug that blocks mu-opioid receptors. It is also very difficult to overdose on buprenorphine as its effects plateau at high doses, and it has fewer interactions with HIV drugs, so is easier to use in patients taking antiretroviral therapy.

“The introduction of buprenorphine, a new medication to treat opioid dependence that has fewer restrictions than methadone, holds promise for reducing HIV transmission and improving the care of patients with opioid dependence and HIV disease,” write the review’s authors, Lynn Sullivan and David Fiellin from Yale University School of Medicine. “Methadone has a long history of proven efficacy and benefits in treating opioid dependence, and the addition of buprenorphine serves to expand the treatment options”.

Buprenorphine has become more widely available over the last ten years. It is taken as a tablet dissolved under the tongue daily or three times a week, and was recently added to the WHO's list of essential drugs. This lists all medicines that should be available in adequate amounts and at an affordable price within all health systems, and are selected according to public health relevance, efficacy, safety and cost-effectiveness.

In their review, the authors summarise the results of cost-effectiveness studies comparing buprenorphine to methadone. These have concluded that buprenorphine treatment programmes may be preferable, both in the treatment of opioid dependence itself, and in its effects on reducing new HIV infections.

However, despite the drug’s benefits, the authors point out that few studies have examined its effects on HIV risk behaviours, such as needle sharing and unsafe sex, although larger scale studies are planned.

In injection drug users (IDUs) who are already HIV-positive, there is evidence from the French Manif 2000 cohort study that use of buprenorphine improves adherence to antiretroviral drugs. Although this was not associated with a better response to therapy, and over half of the patients reverting to drug use during the study, they point out that, despite limited evidence, buprenorphine is less likely to interact with HIV drugs than methadone.

AZT (zidovudine, Retrovir) and some protease inhibitors may increase buprenorphine levels, but the pharmacological properties of buprenorphine mean that its effects are not increased above a ‘ceiling’ level, so increased buprenorphine levels are unlikely to cause dangerous side-effects. However, the authors write, “as efforts continue with the goal to integrate use of buprenorphine into HIV care, further studies will need to be undertaken to make more than theoretical statements about these interactions.”

In conclusion, there is room for substantial optimism about the inclusion of buprenorphine in the treatment of IDUs for the prevention of HIV transmission and the treatment of IDUs who are already HIV-positive. Although the practicalities of treatment programmes remain to be fully evaluated, many of the questions surrounding the drug’s role will be answered in ongoing and future studies.

“In the meantime, office-based clinicians, for the first time in nearly 100 years, have the opportunity to provide a unique treatment to minimise the adverse impact of opioid dependence,” the authors conclude.