Tracy Swan, Treatment Action Group

HIV and hepatitis C are prevalent among current and former injection drug users (IDUs). For years, activists have been protesting the exclusion of people who use drugs from clinical trials of novel agents for HIV and hepatitis C. Excluding high prevalence populations from all research of new treatments is unacceptable, unless there is a compelling safety reason to do so.

Recently, exclusion criteria have become slightly less restrictive in some cases, leaving the investigator holding the bag, as it were. He or she is empowered to decide whether a person’s drug and/or alcohol use, dependence or abuse will interfere with the ability to participate in a trial—or if it could endanger study volunteers.

In theory, this is progress, but in practice, the impact is limited. Concerns about adherence and drug-drug interactions need to be addressed. Regular attendance at clinic visits may be a good indicator for the ability to participate in a clinical trial, rather than whether or not a person is using drugs and/or alcohol. Drug and alcohol use, dependence and abuse are not the same, and should be assessed with validated, easy-to-use tools such as the AUDIT-C. It may be possible to identify drug-drug interactions by in vitro studies—and if not, a safe way to gather this information must be determined.

Some drug-and alcohol-related exclusion criteria have become gospel, although the information they are based on may be limited or outdated. These have rendered drug and alcohol users ineligible for approved treatments and interventions, as well as clinical trials. Here are two examples:

• Early HCV treatment trials, using interferon monotherapy, reported poorer outcomes among people who drank before or during HCV treatment versus non-drinkers. [1, 2, 3] Hence, many doctors are unwilling to treat drinkers for hepatitis C, despite newer information, and more effective HCV treatment. Two recent studies, which used interferon plus ribiavirin), reported that people who drank prior to, or during HCV treatment responded as well as non-drinkers. [4, 5]
• Although recent alcohol and/or drug use is considered a “relative” contraindication for liver transplantation in the United States, candidates with a history of substance abuse must be abstinent for six months before they are put on the waiting list. [6] This delay may be fatal for some people ,since the chronic shortage of donor organs may mean a long wait. However, a recent study did not find any difference in survival of liver transplant recipients who resumed substance use versus those who remained abstinent after transplantation. [7]

HIV and hepatitis C trials for people who use drugs

The following listing of studies that are currently recruiting-or soon to open is compiled from:

http://clinicaltrials.gov

Unless listed under “international”, these trials are in the United States.

Listing these trials is not an endorsement or comment on either the research or trial design.

International

• Adolescent Drug and HIV Prevention in South Africa
• Methadone Maintenance & HIV Risk in Ukraine
• Naltrexone and Adrenergic Agents to Reduce Heroin Use in Heroin Addicts
• Project HERMITAGE: HIV Prevention in Hospitalized Russian Drinkers
• Addiction Treatment in Russia: Oral vs. Naltrexone Implant
• Hepatitis C Among Opioid addicts in Opioid maintenance Treatment in Zurich, Switzerland (HepCOP)

Prevention/Drug Treatment (HIV status not specified unless noted)

• Computer-Assisted HIV Prevention for Young Drug Users
• Treatment of Heroin and Cocaine With Methadone Maintenance and Contingency Management Users
• Drug Treatment Combined With Drug and Risk Reduction Counseling in the Prevention of HIV Infection Among Injection Drug Users (HIV negative)

Prisoners

• Prison Buprenorphine
• Effectiveness of Opiate Replacement Therapy Administered Prior to Release From a Correctional Facility – 1
• Buprenorphine Maintenance for Opioid-Addicted Persons in Jail and Post-Release (males only)
• Hepatitis C (HIV status not specified unless noted)
• A Video-Based HCV Curriculum for Drug Users
• Improving Hepatitis C Treatment in Injection Drug Users
• Study of the Effects of Motivational Enhancement Therapy on Alcohol Use in Chronic Hepatitis C Patients
• Treatment of Acute Hepatitis C Virus Infection With Pegylated Interferon in Injection Drug Users (for HIV-negative people only)

HIV Positive Women

• Brief Therapy Intervention for Heavy/Hazardous Drinking in HIV-Positive Women

HIV Positive or At-Risk Men

• Mirtazapine to Reduce Methamphetamine Use Among MSM With High-Risk HIV Behaviors
• Aripiprazole Treatment for Methamphetamine Dependence Among High-Risk MSM
• Acceptability of Pharmacologic Treatment for Methamphetamine Dependence Among MSM
• Behavior Change and Maintenance Intervention for HIV+ MSM Methamphetamine Users
• 12 Week Group Therapy Intervention for HIV+ Methamphetamine Users and Deliver It Within an HIV/AIDS Primary Care Setting.
• Behavioral Therapy Development for Methamphetamine Abuse
• Addressing Young Men’s Substance Use and HIV Risk

HIV-Positive: Women and Men

• Comparison of HIV Clinic-Based Treatment With Buprenorphine Versus Referred Care in Heroin-Dependent Participants
• Buprenorphine and Integrated HIV Care Evaluation
• Directly Administered HIV Therapy in Methadone Clinics
• Skills Based Counseling for Adherence and Depression in HIV+ Methadone Patients – 1
• The Effects of Nutritional Supplementation and Drug Abuse on HIV
• Pharmacotherapy for HIV+ Stimulant Dependent Individuals
• The CORE Buprenorphine Project – An HIV Primary Care Program Demonstration
• Buprenorphine HIV Care Integration Project

References
1. Mochida S, Ohnishi K, Matsuo S, Kakihara K, Fujiwara K. Effect of alcohol intake on the efficacy of interferon therapy in patients with chronic hepatitis C as evaluated by multivariate logistic regression analysis. Alcohol Clin Exp Res. 1996 Dec;20(9 Suppl):371A-377A.
2. Ohnishi K, Matsuo S, Matsutani K, et al. Interferon therapy for chronic hepatitis C in habitual drinkers: comparison with chronichepatitis C in infrequent drinkers. Am J Gastroenterol. 1996 Jul;91(7):1374-9.
3. Okazaki T, Yoshihara H, Suzuki K, et al. Efficacy of interferon therapy in patients with chronic hepatitis C. Comparison between non-drinkers and drinkers. Scand J Gastroenterol. 1994 Nov;29(11):1039-43.
4. Anand BS, Currie S, Dieperink E, et al; VA-HCV-001 Study Group. Alcohol use and treatment of hepatitis C virus: results of a national multicenter study. Gastroenterology. 2006 May;130(6):1607-16.
5. Schaefer M, Schmidt F, Folwaczny C, et al. Adherence and mental side effects during hepatitis C treatment with interferon alfa and ribavirin in psychiatric risk groups. Hepatology. 2003 Feb;37(2):443-51.
6. Lucey MR, Brown KA, Everson GT, et.al. Minimal Criteria for Placement of Adults on the Liver Transplant Waiting List: A Report of a National Conference Organized by the American Society of Transplant Physicians and the American Association for the Study of Liver Diseases. Liver Transpl Surg. 1997 Nov;3(6):628-37.
7. Nickels M, Jain A, Sharma R, et al. Polysubstance abuse in liver transplant patients and its impact on survival outcome. Exp Clin Transplant. 2007 Dec;5(2):680-5.