In the last few years, Russia has made some progress toward ensuring access to antiretroviral drugs for those in need. Even in a place like Kuznetsk, a remote and dilapidated town several hundred miles south-west of Moscow, an increasing number of people living with HIV is starting treatment. These people include injection drug users who, until recently, were routinely told that they were not deserving of ART or even specifically excluded from ARV programs. Yet, Russian injection drug users by no means have equitable access to ARV. As Larisa Badrieva and Konstantin Lyazhentsev point out in an article in the last edition of ARV4IDU, many barriers to access persist, with the lack of maintenance treatment chief among them.

Earlier this year, Human Rights Watch conducted research in three Russian regions to take a closer look at the drug dependence treatment system. We found that the vast majority of drug dependent people in Russia do not have access to evidence-based medical care to treat their dependence. As a result, many drug users who might otherwise have successfully entered into treatment programs are condemned to a life of continued drug use with its increased risk of HIV infection, other drug-related health conditions, and death by overdose. Undoubtedly, the lack of adequate drug dependence treatment will also result in some drug users dropping out of ARV treatment programs or having difficulty adhering to the treatment regimen.

Illicit drug use is a serious problem in Russia today, with estimates of the numbers of users ranging between 3 and 6 million people.  Many of these people—though by no means all—have developed drug dependence, a serious chronic, and often relapsing, disease as a result of prolonged drug use.  More than ten percent of injection drug users are living with HIV, and about seventy percent with hepatitis C. As is the case with people affected by other diseases, persons dependent on drugs have a right to medical care for their condition, both under Russian and international law.

Russia has an extensive system of state substance abuse clinics that offer services for alcohol and drug dependence and has, in the past few years, invested considerable funds into the development of rehabilitation centers for people dependent on drugs. Yet, our detailed field studies in Kazan (Republic of Tatarstan), Kaliningrad, and Penza, shows that the services offered at state clinics in Russia are generally of poor quality and not consistent with international best practices in the field of drug dependence treatment. This is due to policy decisions that Russia has made with regard to the provision of medical treatment that restrict the availability and accessibility of drug dependence treatment services, and affect their appropriateness and quality.

While detoxification treatment is widely available throughout Russia, rehabilitation treatment remains unavailable in many parts of the country. Private drug dependence clinics, some of which offer evidence-based rehabilitation treatment, are often unaffordable for drug users. Various obstacles keep drug users away from seeking treatment at state clinics, including the risk of restrictions on civil rights by being registered as a drug user, breaches of confidentiality associated with treatment, and a widespread distrust of drug treatment services that also undermines take-up rates. The treatment offered at detoxification clinics does not follow lessons learned from decades of research on effective drug dependence treatment modalities. On the contrary, policy decisions relating to what drug treatment programs can be offered deliberately ignore the best available medical evidence and recommendations, and as such arbitrarily restrict drug users’ access to appropriate health care.

Despite these important failings of the drug dependence treatment system in Russia, healthcare institutions, policy makers, and the Russian public routinely blame drug users for the failure to overcome their drug dependence. In its research, Human Rights Watch was repeatedly told that drug users simply lack the motivation, character, or perseverance to stop using drugs. Various officials are currently advocating new laws and policies that would enable the state to force drug users to undergo treatment. Undoubtedly, some drug users do not want to end their drug habit. But various studies show that almost all drug users in Russia who have used drugs for more than one year have made multiple attempts to stop using, either at healthcare facilities or on their own. Every single one of the around 60 drug users Human Rights Watch interviewed for this report had made at least one attempt to stop, and many had made multiple attempts. A young woman in Kazan expressed exasperation at both the drug treatment system and her own dependence:

I’m not going back there. There’s no point, they don’t cure you. I would go to the detoxification clinic if they actually helped [me] there. I’m sick and tired of injecting. But I can’t do it [withdraw] at home… I would like to live to 30 at least…
Svetlana S. (a pseudonym), 25 years old

Studies repeatedly demonstrate, however, that, no matter how strong a drug-dependent person’s motivation to address his or her drug use, the odds are that he or she will not succeed without access to an evidence-based drug dependence treatment program. Drug dependence is a chronic disease that often relapses, even for drug users who participate in proven treatment programs and are committed to their treatment. For many people affected by the disease, there are biological and psychological reasons why will power does not suffice to overcome the disease—just as people who suffer from depression cannot overcome their condition on will power alone but need medications, therapy, or a combination of the two.

A considerable part of the blame for the drug dependence treatment gap thus lies with the Russian government and Russia’s healthcare system, which leave most drug users who wish to stop using drugs or to gain control over their addiction to their own devices in the face of a serious chronic disease. As a result, many drug users who might otherwise have successfully entered into treatment programs are condemned to a life of continued drug use with its increased risk of HIV infection, other drug-related health conditions, and death by overdose. But Russian society also pays a price for the state’s failure to provide easily accessible and evidence-based drug dependence treatment services. In other countries, evidence-based treatment of drug users has been shown to lead to considerable savings on drug-use-related law enforcement efforts, incarcerations of drug users, and healthcare costs due to HIV, hepatitis C and other drug-related health conditions.

The right to health, which Russia has explicitly recognized in its constitution and by becoming party to various international human rights conventions, requires states to make healthcare services available for people affected by disease, including by drug dependence. These services must be accessible—without discrimination—for people who need them, and have to be culturally and ethically acceptable, scientifically and medically appropriate, and of good quality. Although the right to health, in recognition of the great variation in resource availability in different countries, is not prescriptive about a specific standard of care that has to be provided, states are obliged to work toward full realization of the right and to progressively improve the care offered. A rights-based health policy also requires states to ensure that policy decisions and choices are objective and evidence-based, directed towards maximizing the right to health of individuals, and not made on criteria that are discriminatory, arbitrary, or have an unjustifiably restrictive or negative impact on the enjoyment of the right to health, in comparison to other available policy options.

Availability of drug dependence treatment is mixed in Russia. While there are narcological clinics in all major towns of Russia, most of these clinics offer only detoxification, which, on its own, does little to help a drug user achieve a lasting remission.  State-run rehabilitation or relapse prevention centers, which provide the crucial second phase of drug dependence treatment by helping drug users manage psychological craving for drugs, exist in only 26 of Russia’s 86 regions. In some regions commercial or faith-based rehabilitation centers exist, but treatment at the former is often too expensive for drug users while many drug users do not feel comfortable using the latter.

One of the most effective and best-researched drug dependence treatment modalities for opiate dependence known today, methadone or buprenorphine maintenance treatment, is altogether unavailable in Russia. Although dozens of countries have successfully used these medications in the treatment of drug- dependent persons for several decades and the World Health Organization and the United Nations Office on Drugs and Crime have strongly endorsed them, their use is explicitly prohibited by law in Russia. Top officials in Russia, including in the healthcare sector, oppose their use on the mostly ideological ground that it substitutes one drug for another. The policy decision not to make methadone and buprenorphine available for the treatment of drug-dependent persons, based on factors that ignore medical evidence, can only be described as arbitrary and unreasonable, and as such is a failure of Russia’s obligation to fulfill the right to health.

Accessibility of treatment, the second requirement under the right to health, is highly problematic in Russia. Whereas research indicates that drug treatment services should be easily accessible so as to ensure that as many drug users make use of them as possible,  in Russia numerous barriers exist that keep drug users away from these services. Most drug users distrust state narcological clinics; they do not believe that the treatment offered is effective, and see the clinic staff as corrupt and uninterested in their recovery. State narcological clinics in the regions we visited have done little to counter this distrust. A central, and easily remedied, obstacle to treatment seeking is the fact that clinics in all three regions tell drug-dependent persons who voluntarily seek help—behavior that states should clearly encourage—that unless they pay for their own treatment, their names will be entered into a database of people considered to be drug dependent—under Russian law, all drug users who seek free treatment at state narcological clinics are placed on this state drug user registry—and that consequently certain restrictions will be imposed on their rights. Other factors that keep drug users away from state narcological clinics are the cost of paid treatment, including out-of-pocket charges for medications patients are supposed to receive for free, the requirement to collect paperwork on various health conditions prior to admission, and poor conditions in the clinics. Most drug users therefore do not believe that the treatment offered is effective, and they see the clinic staff as corrupt and uninterested in their recovery. State narcological clinics in the regions we visited have done little to counter this distrust.

Russia also fails to meet the requirement that treatment services offered be “scientifically and medically appropriate, and of good quality.” Decades of research into drug dependence treatment have created a vast body of evidence on the effectiveness of various treatment approaches. These findings have been summarized, among others, in the United Nations Office on Drugs and Crime’s “Drug Dependence Treatment Toolkit.” Yet, Russia has made little effort to incorporate lessons learned into its drug dependence treatment services.

Research findings, for example, underscore the fundamental importance of beginning psychosocial interventions with patients during the detoxification stage to motivate them to stay in treatment after detoxification is over.  However, we found that this hardly happens in Russia’s drug dependence clinics. First of all, patients are generally heavily medicated with tranquillizers and antipsychotic medications, even if research shows that this is not necessary for most patients.  As a result, patients are often in a reduced state of consciousness, making counseling efforts difficult or even pointless. Secondly, we found that only very limited counseling took place. Most drug users said that a psychologist or peer counselor from a rehabilitation center had talked to them about the possibility of continuing treatment but that that was the extent of psychosocial interventions. Various drug users mentioned extreme boredom while in the detoxification clinic. Patients are also generally not counseled on HIV while in the detoxification clinics, although best practice standards for drug dependence treatment recommend that such counseling take place.  Research also demonstrates the high effectiveness of methadone and buprenorphine maintenance programs, which, as mentioned above, are prohibited in Russia.

There is ample evidence that the state drug dependence treatment system in Russia is largely ineffective. In a 2006 survey of almost 1,000 injection drug users in 10 Russian regions conducted by the Penza Anti-AIDS Foundation, 59 percent of drug users who had made use of the state treatment system had gone back to using drugs within a month of finishing their treatment course; more than 90 percent had relapsed within a year. Various other studies also found that less than 10 percent of patients of state narcological clinics remain in remission a year after their treatment.  Indeed, Human Rights Watch interviewed drug users in each of the regions visited for this report who told us that they had gone back to using drugs within days of their release from the detoxification clinic. Using other measures of treatment effectiveness, such as the treatment system’s ability to recruit patients and retain them for a length of time adequate for appropriate treatment, the Russian system fares equally poorly.

Some narcological clinics in Russia also appear to routinely violate the privacy rights of those who try to access them. Governments and their agents are required to observe confidentiality of medical information. It appears, however, that some state narcological clinics in Russia share information on patients who are on the state drug user registry with law enforcement and other government agencies. The Penza Anti-AIDS Foundation survey found that respondents in many of the 10 regions surveyed believed that narcological clinics had shared information on them with others, mostly law enforcement agencies.  The routine sharing of medical information of drug users violates the acceptability component of the right to health, and the right to privacy protected under the European Convention on Human Rights, to which Russia is a party.

Human Rights Watch also found that Russia imposes unnecessary restrictions on the rights of people on the drug user registry, such as the right to obtain a driver’s license or hold certain jobs, and thereby violates the principle of non-discrimination. While the rationale behind these restrictions—public safety—may in principle appear to be legitimate, the restrictions are imposed selectively only on those drug users who have to avail of free treatment at state clinics because they cannot afford to pay for treatment services. Whether a patient can pay for services is not a legitimate criterion on which to determine that private information about them should be retained on a registry and be used to restrict certain civil rights. Furthermore, the restrictions are disproportionate as they are imposed for a five-year period without any assessment whether there is a need to impose them on the individual in question or any periodic review to determine whether that need continues to exist.

The close links between injection drug use and HIV infection add extra urgency to the need for effective drug dependence treatment. Injection drug users make up an estimated 65 to 80 percent of all persons living with HIV in Russia and around 10 percent of injection drug users in Russia are HIV-positive. Effective drug dependence treatment has been shown to help reduce HIV infections as patients may either stop using drugs altogether or may adopt less risky injection behavior. Today, as Russia is rapidly expanding access to antiretroviral (ARV) treatment for people living with HIV, effective drug treatment programs, including methadone maintenance therapy and drug-free programs, could play an important role in aiding drug users in accessing and adhering to ARV treatment. If Russia does not take steps to address the problems of its drug dependence treatment system, it runs the risk of continued and increasing spread of HIV, and even drug resistant HIV strains, due to lack of access by drug users to ARV and their suboptimal adherence due to poor quality drug dependence treatment programs.

Russia needs to take urgent steps to address the various failings identified in this report, and reform its drug dependence treatment system in accordance with the findings of scientific evidence. Human Rights Watch makes the following key recommendations:

• Immediately lift the ban on the medical use of methadone and buprenorphine in the treatment of drug dependence and introduce maintenance therapy programs.
• Integrate evidence-based drug treatment policies into the drug treatment system.
• Adopt and fund a federal plan aimed at increasing the availability of rehabilitation treatment by opening new rehabilitation programs and centers in regions that do not currently have any. This plan should have a clear timeline and benchmarks for implementation, and should prioritize regions and towns on the basis of need.
• Take steps to ensure drug users can enter treatment without delay. This should include measures to remove arbitrary requirements to present certificates on various health conditions upon admission, and steps to minimize, to the extent possible, waiting lists for admission.
• Provide adequate funding to narcological clinics and cease out-of-pocket charges for medications that should be provided free of charge.
• Reform the detoxification treatment protocol to end overmedication of patients and introduce clear guidance on psychosocial interventions aimed at patient retention.
• Take steps to ensure all patients in detoxification receive proper counseling on HIV and other diseases that are prevalent among drug users.
• Take active steps to counter distrust toward state narcological clinics among drug users. These should include the adoption of a patient bill of rights, clear guidelines on treatment options and costs, and steps to root out corrupt practices by clinic doctors.
• Reform the drug user registry to remove blanket restrictions on rights of people on the registry.
• Take steps to ensure respect for confidentiality of medical information.

This article was based on an initial post to the HRW website

English

http://www.hrw.org/en/news/2007/11/07/russia-drug-addiction-treatment-requires-reform

Russian

http://www.hrw.org/en/news/2007/11/06

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.

a. British Columbia Centre for Excellence in HIV/AIDS; b. Department of Medicine, University of British Columbia

Almost a decade ago, over 150 United Nations members (including Great Britain, the United States and Canada) joined together and signed a declaration committing them to achieving a ‘drug free world’ by 2008. After investing billions of dollars toward this goal, prohibition (a.k.a. ‘the war on drugs’) has failed to meet its objective of eliminating or even significantly reducing the availability of illegal drugs. Despite this, enforcement and incarceration remain the dominant approaches to drug policy throughout the world, including in those regions hardest hit by injection drug use-driven HIV epidemics, such as the former Soviet Union and Southeast Asia. [1]

The reliance on enforcement has consistently been shown to increase rather than decrease the harms associated with injection drug use, including risks for HIV infection. For example, commonly applied law enforcement strategies such as police crackdowns in drug markets have been found to increase the stigmatisation of people who use drugs and also undermine public health efforts by pushing drug users away from health and social services, including syringe exchanges. Further, a large number of studies have demonstrated that injection drug users (IDU) are often reluctant to access syringe exchanges or carry syringes on their person out of fear of arrest, and that sterile syringes are often confiscated by police. Such effects, not surprisingly, have been associated with increased rates of syringe sharing. Lastly, when police presence increases in drug markets, IDU are known to rush during the injection process to avoid confrontation with police, and in doing so often skip important steps in the injection process. For example, IDU may be less likely to clean injection sites prior to injection or dress wounds afterward, and risk of vascular damage increases as syringes are inserted in a hurried manner. These practices substantially increase risks for abscesses and bacterial infections, a problem that has been previously found to account for a majority of hospitalizations among IDU. [1]

While previous research examining the harms associated with drug enforcement has focused primarily on policing, a growing body of research is now pointing to the harms associated with incarceration. [2]

Some of the earliest work in this area focused on high risk injecting occurring in prisons, and eventually research from a handful of settings found incarceration to be strongly associated with HIV infection among IDU. This led to the establishment of prison-based needle exchanges in many settings, which have since been found to be effective in reducing syringe sharing. [3]

More recently, a growing number of researchers have been turning their attention to the impact of incarceration on HIV treatment among IDU.

It has been well-established that HIV positive IDU populations have low levels of HIV treatment up-take as well as high rates of treatment discontinuation relative to other HIV-positive populations. In Canada, we found that 50% of HIV-positive IDU participating in the Vancouver Injection Drug Users Study (VIDUS) prematurely discontinued HIV treatment. [4]

Although there are a range of potential explanations for poor adherence to HIV treatment among IDU, recent investigations indicate that interactions with the criminal justice system (primarily incarceration) are a contributing factor. In a study of 160 HIV-positive IDU in Vancouver, IDU who reported having been recently incarcerated were almost 5 times more likely to prematurely discontinue HIV treatment than those who had not experienced recent incarceration. [4]

Among all study participants who prematurely discontinued treatment, the most commonly cited reason for discontinuation was being in jail, with 44% of participants citing this reason. The second most commonly cited reason was problems with side-effects (41%). Reasons for discontinuing treatment that were cited by a smaller number of participants included being fed up with HAART (7%) and interactions with methadone (3%).

The evidence regarding incarceration and HIV treatment is not, however, entirely consistent. For example, in contrast to research undertaken in Vancouver, studies conducted in the United States, specifically Rhode Island, found that HIV-positive individuals incarcerated for 6 months or longer and receiving HIV therapy throughout this time experienced a reduction in their viral load and an increase in their CD4 lymphocyte counts – both strong indicators of successful treatment and adherence to HIV therapy. [5]

While this finding may appear to contradict other research, a recent study conducted in Vancouver by Palepu and colleagues has shown that individuals with extended prison sentences were more likely than those with shorter sentences to achieve virological suppression. [6]

More specifically, these authors found that IDU with a history of incarceration within 12 months of initiating HAART had a reduced likelihood of achieving HIV-1 RNA suppression. This is concerning as the majority of incarceration events experienced by IDU in many setting are relatively brief. In Canada, statistics indicate that the incarceration period for 70% of drug possession cases is 30 days or less and the incarceration period for 64% of drug trafficking cases is 6 months or less. [7. 8]

Given the research of Palepu and colleagues, the short duration of the majority of drug-related sentences are likely to interfere with the delivery of HIV treatment. In addition, research suggests that post-incarceration transitions back to community pose further risks to HIV therapy success among IDU. [5]

Clearly, these finding suggest that interactions with the criminal justice system are negatively affecting adherence and subsequently hindering treatment success among IDU populations. Potential explanations for low adherence in prison settings, while not fully evaluated, include: HIV-related discrimination and fear of disclosure, routines in prison that are not conducive to adherence, and poor delivery of HIV treatment within prisons. It has been argued that the structural characteristics of prisons and the associated routines make maintaining a treatment regimen in prison challenging. The dispensing intervals and dietary requirements associated with some regimens may not be easily accommodated within prisons, and prisoners may also be likely to miss medications if they go to court, are transferred, or released. It has also been suggested that prisoners may avoid taking treatment in prison in an effort to conceal their HIV status. [4]

It is well known that disclosure of HIV positive status in prison settings can result in significant negative consequences (e.g., intimidation, violence) for prisoners, and HIV-positive prisoners have been known to voluntarily enter protective custody to ensure their safety. [9]

Lastly, disclosure of HIV status may limit an active IDU’s access to shared drugs and syringes within prisons. [2]

In light of these issues, it is clear that efforts should be made to ensure that HIV-positive prisoners are given additional support designed to prevent premature discontinuation of treatment. In particular, efforts should be made to ensure that HIV-positive prisoners receive medications in a manner that preserves privacy, accommodates dietary requirements, and responds to changes in prison routines. As well, in order to reduce concerns regarding the impact of HIV disclosure on access to syringes, prison-based needle exchanges should be implemented more widely.

The impact of incarceration, sentence length and prison-release on HIV treatment adherence and outcomes warrants further investigation. However, it is already clear that much more must be done to ensure that prisoners receive and benefit from HIV treatment during all interactions with the criminal justice system and upon release prison.

References

1. Kerr T, Small W, Wood E. The public health and social impacts of drug market enforcement: A review of the evidence. International J Drug Policy. 2005;16:210-220.
2. Small W, Wood E, Jurgens R, Kerr T. Injection drug use, HIV/AIDS and incarceration: evidence from the Vancouver Injection Drug Users Study. HIV AIDS Policy Law Rev. Dec 2005;10(3):1, 5-10.
3. Kerr T, Wood E, Betteridge G, Lines R, Jurgens R. Harm reduction in prisons: a ‘rights-based analysis’. Critical Public Health. 2004;14(4):345-360.
4. Kerr T, Marshall A, Walsh J, Palepu A, Tyndall M, Montaner J, Hogg R, Wood E. Determinants of HAART discontinuation among injection drug users. AIDS Care. Jul 2005;17(5):539-549.
5. Springer SA, Pesanti E, Hodges J, Macura T, Doros G, Altice FL. Effectiveness of antiretroviral therapy among HIV-infected prisoners: reincarceration and the lack of sustained benefit after release to the community. Clin Infect Dis. Jun 15 2004;38(12):1754-1760.
6. Palepu A, Tyndall MW, Chan K, Wood E, Montaner JS, Hogg RS. Initiating highly active antiretroviral therapy and continuity of HIV care: the impact of incarceration and prison release on adherence and HIV treatment outcomes. Antivir Ther. Oct 2004;9(5):713-719.
7. La Prairie C, Gliksman L, Erickson PG, Wall R, Newton-Taylor B. Drug treatment courts-a viable option for Canada? Sentencing issues and preliminary findings from the Toronto court. Substance Use and Misuse. 2002(37):1529-1566.
8. Canada S. Adult criminal court data tables 1998/99. Ottawa: Canadian Centre for Justice Statistics; 2000.
9. Jürgens R. HIV/AIDS in Prisons: Final Report. Montreal: Canadian HIV/AIDS Legal Network; 1996.

Introduction

HIV/AIDS and opioid dependence adversely impact millions of people throughout the world. Explosions in both epidemics are described worldwide and there is no evidence of slowing. As a result, HIV-infected opioid dependent prescribed either methadone or buprenorphine for the treatment of their opioid dependence, may find themselves prescribed antiretrovirals (ARVs) that may result in an adverse interaction. Awareness that pharmacokinetic interactions exist may deter some patients and physicians from initiating potentially life-saving therapy, or lead to adverse consequences among patients already receiving treatment. The reader is pointed to recent reviews that provided greater details regarding interactions between ARVs, treatments for opioid dependence, and drugs of abuse/dependence. [1, 2]

Following is a summary of the key interactions and their management.

Methadone

Methadone, a full opioid agonist, is used for the treatment of pain and opioid dependence. Multiple cytochrome P450 isoenzymes are involved in the metabolism of methadone. [3-6]

The currently approved nucleoside reverse transcriptase inhibitors (NRTIs) do not affect methadone levels in a clinically significant manner and do not precipitate opioid withdrawal and do not result in opioid excess. However, methadone affects the pharmacokinetics of several of the NRTIs. Specifically, several studies have demonstrated that methadone increases zidovudine (ZDV) by approximately 40%. [7-10]

This increase may result in side effects, such as headache, abdominal pain, myalgias, and fatigue, which can all mimic opioid withdrawal. In addition, laboratory abnormalities, such as anemia and hepatitis, may occur due to increased ZDV levels. Results from studies with stavudine (d4T) and didanosine (ddI) have been performed in a between-subject crossover design. [11]

While neither ddI nor d4T affected methadone levels, methadone appeared to alter the dispo­sition of both NRTIs. Although methadone’s decrease in drug levels for d4T was statistically significant, these values are unlikely to be clinically significant. However, methadone’s 66% decrease in the maximum concentration of buffered ddI tablets is clinically significant; the enteric-coated (EC) formulation has corrected this problem and is the preferred formulation when methadone and ddI are co-administered. [12]

In addition to NRTIs, the non-nucleoside reverse transcriptase inhibitors (NNRTIs) nevirapine [13-16] and efavirenz [17-19] are well described in the literature as resulting in the induction of methadone metabolism with resultant opioid withdrawal, often requiring elevations in methadone dosages. Patients taking methaodone who are started on nevirapine or efavirenz should be monitored for signs of opioid withdrawal.

With the exception of tipranavir, the currently available protease inhibitors (PIs) appear to lack significant interactions with methadone. Tipranavir’s package insert states that co-administration of tipranavir boosted with ritonavir and methadone could result in a 50% decrease in the methadone concentration which may require increases in methadone in some patients. [20]

However, the applicability of this study for patients on chronic methadone maintenance is unclear as this study was conducted in opioid-naïve healthy volunteers after a single dose of methadone. [2]

Studies examining other FDA approved classes, namely CCR5 antagonist, maraviroc and integrase inhibitor, raltegravir have not been performed to date.

Buprenorphine

Buprenorphine (BUP) is a partial opioid agonist used for the treatment of opioid dependence. BUP undergoes N-dealkylation to norbuprenorphine by cytochrome P450 isoenzyme 3A4 and these metabolites are glucuronidated by UGT1A1. [21. 22. 23]

Two recent reviews have delineated all the ARVs studied to-date with buprenorphine. [1, 2]

In summary, compounds that lower buprenorphine levels appear not to affect the pharmacodynamic properties of buprenorphine. This was demonstrated in efavirenz’s ability to lower buprenorphine concentrations without precipitating withdrawal. [24]

In addition, compounds that elevate buprenorphine levels, such as ritonavir and delavirdine, appear not to alter buprenorphine’s pharmacodynamic profile as they did not produce opioid excess. [25]

The one exception to this seeming lack of pharmacodynamic interactions with ARVs may be in the case of atazanavir, which shares the UGT 1A1 pathway with BUP. [26. 27]

Although surveillance for opioid excess is encouraged in the co-administration of atazanavir and buprenorphine, the two can be safely administered with appropriate observation.

Studies examining other FDA approved classes, namely CCR5 antagonist, maraviroc, and integrase inhibitor, raltegravir have not been performed to date.

Management of interaction-induced opiod withdrawal or excess

The time course of symptom development due to medication interactions is highly variable. Typically, inhibition of cytochrome P450 enzymes can occur as soon as an inhibiting medication is started, with associated symptoms (typically of opioid excess) appearing shortly thereafter. Induction of P450 isoenzymes occurs more slowly, however, typically taking 10 to 21 days; however, these are general timeframes. When alternative explanations for apparent symptoms of opioid withdrawal or excess have been considered but discounted (e.g., thy­roid dysfunction, new onset of cocaine use, etc.), an empiric change in methadone dose may be indicated with careful follow-up.

Clinicians should not be reluctant to suggest opioid pharmacotherapy dose changes in the absence of definitive data regarding a specific interaction since substantial between subject variation exists. In addition, not all interactions between opioid agonist treatments and single antiretrovirals, let alone typical multi-medication regimens, have been studied. In everyday practice, with patients taking multiple medications for multiple comorbidities, the risk for interactions is significantly greater.

In the United States, patients receiving methadone treatment for opioid dependence are enrolled in licensed methadone maintenance treatment programs (MMTPs). The physician at the MMTP is responsible for prescribing the patient’s methadone. Co-ordination of care between MMTP and HIV care settings is critical.

A common scenario consists of an HIV specialist prescribing antiretroviral therapy to a patient receiving methadone in an MMTP. A phone conversation between the HIV physician and the MMTP physician can be enormously helpful to the patient’s care when a medication interaction is anticipated or suspected. Therefore, when a new antiretroviral known to significantly interact with methadone is started (e.g., efavirenz or nevirapine) in methadone maintained patients, the HIV clinician should contact the prescribing physician at the MMTP immediately to coordinate care. This pre-emptive intervention will allow the MMTP to be alert to the need for a methadone dose increases if withdrawal symptoms are precipitated.

Although exact schedule of increase has not been comprehensively studied, the following guidelines are in agreement with expert opinion. Importantly, dosing may vary from patient-to-patient, as not all patients will develop opiate withdrawal. A reasonable plan is to routinely screen all patients for opiate withdrawal beginning on the fourth day of starting the new antiretroviral medication. Additionally, patients should be alerted to the possibility of precipitated withdrawal so they can notify staff should symptoms develop. If symptoms develop, the methadone dose should be immediately increased by 10 mg every 2-3 days until symptoms abate. Coordinating care between HIV treatment clinician and the MMTP physician can thus minimise the potential negative impact of opiate withdrawal symptoms as a stimulus for non-adherence to antiretroviral therapy or relapse to illicit opioid use. If the inciting antiretroviral is discontinued, the methadone dose should be gradually reduced to pre-treatment levels over the course of one to two weeks.

If available, a serum methadone trough level can inform situations where an interaction may be suspected. If low, this information may assist in reassuring the patient, or the program, that a methadone dose increase is indeed indicated.

However, if a patient is taking zidovudine (ZDV) and methadone and complains of opioid withdrawal, reduction in ZDV dose should be considered first. If drowsiness or other symptoms of methadone excess are reported, a reduction in methadone dose should be considered. A high serum methadone trough level would further support the clinical findings.

In the US, buprenorphine can be prescribed by any physician who has received a waiver from the DEA. The evaluation and treatment of BUP and ARV interactions, therefore, will be managed primarily by HIV practitioners. Due to the long half-life and high binding affinity of BUP, and the initial data presented above, it is anticipated that buprenorphine may have fewer medication interactions with antiretroviral medications than methadone.

Risk reduction

Opioid dependence is a relapsing medical disorder and HIV clinicians should understand that patients on methadone or buprenorphine may relapse into illicit use of substances. The relapsing nature of opioid dependence and the wide array of serious infectious and other medical consequences due to relapse, requires the development of preventive risk reduction strategies. Risk reduction is based on the underlying principle that opioid dependence is a chronic and relapsing disease which may not be cured in the individual or eliminated from society but can be conducted in a way that minimises harm to the user and others.

While complete cessation of drug use remains a laudable goal, reduction in drug use frequency and safer injection practices is more realistic for many drug users until abstinence can be achieved. Risk reduction strategies have been effectively incorporated into some drug treatment programs, syringe exchange programs and safe injection rooms. [28, 29]

There are several practical components inherent to risk reduction strategies. Education about and provision of drug use paraphernalia (e.g., needles and syringes) for more hygienic injection practices for the prevention of infectious complications of injection are essential. In addition to the distribution or exchange of injection equipment, these programs typically include HIVAIDS education, condom distribution, and referral or enrollment in a variety of drug treatment, medical, and social services. [30]

The ultimate goal of risk-reduction strategies should be the reduction or prevention of illicit drug use itself, the development of strategies that will minimise the serious medical consequences of drug misuse, and the development of strategies that will eliminate drug misuse and its root causes. Until we are successful in this arena, we stand little chance of limiting the spread and consequences of HIV disease in this and related populations.

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