Buprenorphine for human immunodeficiency virus/hepatitis C virus-coinfected patients: does it serve as a bridge to hepatitis C virus therapy?

OBJECTIVES: Buprenorphine is associated with enhanced human immunodeficiency virus (HIV) treatment outcomes including increased antiretroviral therapy initiation rates, adherence, and CD4 cell counts among HIV-infected opioid-dependent individuals. Buprenorphine facilitates hepatitis C virus (HCV) treatment in opioid-dependent patients with HCV monoinfection. Less is known about buprenorphine's role in HIV/HCV coinfection. METHODS: We conducted a retrospective chart review to evaluate HCV care for HIV-infected buprenorphine patients in the first 4 years of buprenorphine's integration into a Rhode Island HIV clinic. RESULTS: Sixty-one patients initiated buprenorphine. All had HCV antibody testing; 57 (93%) were antibody-positive. All antibody-positive patients underwent HCV RNA testing; 48 (84%) were RNA-positive. Of these, 15 (31%) were not referred to HCV care. Among chronically infected patients, 3 received HCV treatment after buprenorphine; all had cirrhosis and none achieved viral eradication. At buprenorphine induction, most patients had inadequately controlled HIV infection, with detectable HIV RNA (59%) or CD4 cell count less than or equal to 350/µL (38%). CONCLUSIONS: Buprenorphine has shown limited success to date as a bridge to HCV treatment within an HIV clinic. Buprenorphine's stabilization of opioid dependence and HIV disease may permit the use of HCV therapy over time.

Hepatitis infection in the treatment of opioid dependence and abuse.

Many new and existing cases of viral hepatitis infections are related to injection drug use. Transmission of these infections can result directly from the use of injection equipment that is contaminated with blood containing the hepatitis B or C virus or through sexual contact with an infected individual. In the latter case, drug use can indirectly contribute to hepatitis transmission through the dis-inhibited at-risk behavior, that is, unprotected sex with an infected partner. Individuals who inject drugs are at-risk for infection from different hepatitis viruses, hepatitis A, B, or C. Those with chronic hepatitis B virus infection also face additional risk should they become co-infected with hepatitis D virus. Protection from the transmission of hepatitis viruses A and B is best achieved by vaccination. For those with a history of or who currently inject drugs, the medical management of viral hepatitis infection comprising screening, testing, counseling and providing care and treatment is evolving. Components of the medical management of hepatitis infection, for persons considering, initiating, or receiving pharmacologic therapy for opioid addiction include: testing for hepatitis B and C infections; education and counseling regarding at-risk behavior and hepatitis transmission, acute and chronic hepatitis infection, liver disease and its care and treatment; vaccination against hepatitis A and B infection; and integrative primary care as part of the comprehensive treatment approach for recovery from opioid abuse and dependence. In addition, participation in a peer support group as part of integrated medical care enhances treatment outcomes. Liver disease is highly prevalent in patient populations seeking recovery from opioid addiction or who are currently receiving pharmacotherapy for opioid addiction. Pharmacotherapy for opioid addiction is not a contraindication to evaluation, care, or treatment of liver disease due to hepatitis virus infection. Successful pharmacotherapy for opioid addiction stabilizes patients and improves patient compliance to care and treatment regimens as well as promotes good patient outcomes. Implementation and integration of effective hepatitis prevention programs, care programs, and treatment regimens in concert with the pharmacological therapy of opioid addiction can reduce the public health burdens of hepatitis and injection drug use.

Integrating HCV services for drug users: a model to improve engagement and outcomes.

Although the majority of prevalent and incident cases of hepatitis C are related to injection drug use, drug users often find it difficult to access treatment services because of concerns about adherence and treatment candidacy. In response to the growing epidemic, OASIS, a nonprofit community clinic, developed a successful peer-based HCV group that allowed us to engage, educate, test, and treat hepatitis C in large numbers of drug users, the majority of whom have multiple potential barriers to intervention. Integrating services for hepatitis C, addiction, mental health, and psychosocial problems, the model involves a collaboration of medical providers and peer educators and incorporates elements of other proven behavioural models, including self-help groups, therapeutic communities, and peer interventions. Our results indicate that this peer-based model is successful at engaging, educating, and treating a diverse spectrum of chaotic drug users. We conclude that an integrated, peer-based approach to intervention can engage even the most challenging addicted patients with hepatitis C, and can facilitate their successful screening and treatment.

Education by peers is the key to success.

We are a Latino, a white guy and an African American, and we are all peer educators in the hepatitis C programme at Organization to Achieve Solutions in Substance Abuse, Inc. (OASIS), a not-for-profit medical clinic in Oakland, California. We are all recovering heroin users who got hepatitis C from using needles and we all managed to stop using drugs. In the same way, we all went through hepatitis C treatment; one of us was a sustained responder, one a non-responder, and one a relapsing non-responder who is still on maintenance interferon. We have written this paper to tell our story. We believe that good education about hepatitis C encourages people to take better care of themselves, get tested and treated when necessary, and can motivate them to cut down or stop using drugs. In short, we use hepatitis C to encourage people to get their lives together. Many of the people we have educated go out to the community and educate other people who need it. We invite others to join our struggle, because we never thought we would make it this far.

Adherence to hepatitis C treatment in recovering heroin users maintained on methadone.

OBJECTIVES: Injection drug users are often denied hepatitis C (HCV) treatment due to concerns about adherence, despite limited data about the impact of such common issues as psychiatric illness and intercurrent drug use. We sought to define the impact of these and other potential adherence barriers in a real-world sample of recovering drug users. METHODS: We conducted a prospective observational study of 71 methadone-maintained patients who received interferon and ribavirin combination therapy in a community-based clinic with expertise in treating addictive disorders. Adherence measures were conducted with monthly interview, medication counts, and urine toxicology testing. RESULTS: Overall, 48 (68%) were adherent, and adherent patients were significantly more likely to achieve a sustained virologic response (42 vs. 4% in nonadherent patients). Patients with and without a prior psychiatric history were similarly adherent (64 vs. 72%, respectively, P>0.5), and the initiation of new psychiatric medications during HCV treatment was associated with improved adherence overall (P=0.02) and in patients that did not report a preexisting psychiatric diagnosis (P=0.04). Trend towards reduced adherence in patients without a period of abstinence was seen before initiating HCV treatment, 46 vs. 72% of those who had been abstinent for at least 1 month (P=0.10). Although occasional drug users were similarly adherent to those who were completely abstinent, patients who relapsed to regular drug use showed a significantly lower level of adherence (P=0.03). CONCLUSIONS: We conclude that the majority of methadone-maintained drug users can adhere to HCV treatment, even those with psychiatric illness and relatively limited pretreatment drug abstinence. Lack of pre-HCV treatment drug abstinence and regular drug use during HCV treatment may be relative barriers to medication adherence, but the initiation of psychiatric medications during HCV treatment may be a helpful intervention. This report provides further evidence for an individualized approach to HCV treatment that does not categorically exclude patients with potential barriers such as mental illness and limited drug abstinence.

Hepatitis C for addiction professionals.

A disease whose reputation is often worse than its reality, hepatitis C is usually benign. Most infected individuals do not experience symptoms requiring treatment, and roughly half of those treated will become free of detectable virus for an extended, perhaps permanent, period. Moreover, a growing body of data suggests that drug users can attain successful treatment outcomes, even when not completely abstinent. Addiction professionals belong in the forefront of prevention and management of this disease. We can assist our patients by helping them stabilize their lifestyles, correcting misperceptions about the disease, teaching prevention and health maintenance, promoting access to diagnosis and treatment, monitoring for treatment side effects, and providing encouragement to remain in treatment.

Cannabis use improves retention and virological outcomes in patients treated for hepatitis C.

OBJECTIVES: Despite the widespread use of polypharmacy, the management of hepatitis C virus (HCV) treatment-related side-effects is often incomplete, and many patients turn to cannabis for symptom relief. Unfortunately, there are few data about cannabis use on treatment outcomes, leaving clinicians without the data needed to inform recommendations. METHODS: To define the impact of cannabis use during HCV treatment, we conducted a prospective observational study of standard interferon and ribavirin treatment in 71 recovering substance users, of whom 22 (31%) used cannabis and 49 (69%) did not. RESULTS: Seventeen of the 71 study patients (24%) discontinued therapy early, one cannabis user (5%) and 16 non-users (33%) (P=0.01). Overall, 37 patients (52%) were end-of-treatment responders, 14 (64%) cannabis users and 23 (47%) non-users (P=0.21). A total of 21 out of 71 (30%) had a sustained virological response: 12 of the 22 cannabis users (54%) and nine of the 49 non-users (18%) (P=0.009), corresponding to a post-treatment virological relapse rate of 14% in the cannabis users and 61% in the non-users (P=0.009). Overall, 48 (68%) were adherent, 29 (59%) non-users and 19 (86%) cannabis users (P=0.03). Although cannabis users were no more likely than non-users to take at least 80% of the prescribed interferon or ribavirin, they were significantly more likely to remain on HCV treatment for at least 80% of the projected treatment duration, 95 versus 67% (P=0.01). CONCLUSIONS: Our results suggest that modest cannabis use may offer symptomatic and virological benefit to some patients undergoing HCV treatment by helping them maintain adherence to the challenging medication regimen.

Approaching treatment for hepatitis C virus infection in substance users.

Although injection drug users represent the majority of incident and prevalent cases of hepatitis C, most lack access to treatment because of concerns about adherence, treatment efficacy, and reinfection. On the basis of an increasing body of evidence suggesting that injection drug users can successfully undergo treatment for hepatitis C virus (HCV) infection, the 2002 National Institutes of Health Consensus Statement on Hepatitis C has recommended that substance users, even those with ongoing drug use, be considered for treatment for HCV infection on a case-by-case basis. However, the criteria on which these treatment decisions should be based are unclear: The duration of pretreatment drug abstinence, comorbid psychiatric illness, intercurrent drug use, and the potential for injected interferon to cause relapse of drug use may all influence results of treatment for HCV infection. This overview summarizes my group's current data about treatment for HCV infection in substance users and the effect of these potential barriers on outcomes of treatment.

The impact of barriers to hepatitis C virus treatment in recovering heroin users maintained on methadone.

Although most cases of hepatitis C virus (HCV) infection are associated with injection drug use, there are few data regarding the impact of putative barriers such as psychiatric disease and intercurrent drug use on HCV treatment outcomes. To define the impact of characteristics often cited as reasons for withholding HCV treatment, we studied HCV treatment in a real world sample of 76 recovering heroin users maintained on methadone. Overall, 21 (28%) had a sustained virological response and 18 (24%) discontinued treatment early. Although there was a modest decrement in response rates in patients reporting a preexisting psychiatric history (p = .01), neither intercurrent drug use nor short duration of pretreatment drug abstinence led to significant reductions in virological outcomes (p = .09 and p = .18, respectively.) We conclude that injection drug users can be safely and effectively treated for HCV despite multiple barriers to treatment when they are treated in a setting that can address their special needs.

Treating hepatitis C virus infection in active substance users.

Although injection drug users represent the majority of new and existing cases of infection with hepatitis C virus (HCV), many lack access to treatment because of concerns about adherence, effectiveness, and reinfection. On the basis of on a small but increasing body of evidence showing that injection drug users can undergo treatment for HCV infection successfully, the 2002 National Institutes of Health Consensus Statement on Hepatitis C has recommended that substance users be treated for HCV infection on a case-by-case basis. However, the criteria on which these treatment decisions should be made are unclear. The duration of pretreatment abstinence, concurrent psychiatric illness, intervening drug use, and the potential for injected interferon to cause relapse of drug use may all influence results of treatment for HCV infection. This overview presents preliminary data on the impact of these potential barriers on outcomes of treatment for HCV infection.

Co-occurring Hepatitis C, substance use, and psychiatric illness: treatment issues and developing integrated models of care.

Hepatitis C virus (HCV) infection is transmitted by injection drug use and associated with psychiatric conditions. Patients with drug use or significant psychiatric illness have typically been excluded from HCV treatment trials noting the 1997 National Institutes of Health Consensus Statement on HCV that indicated active drug use and major depressive illness were contraindications to treatment of HCV infection. However, the 2002 NIH Consensus Statement recognized that these patients could be effectively treated for HCV infection and recommended that treatment be considered on a case-by-case basis. Treating HCV infection in these patients is challenging, with drug use relapse possibly leading to psychosocial instability, poor adherence, and HCV reinfection. Interferon therapy may exacerbate preexisting psychiatric symptoms. Co-occurring human immunodeficiency virus or hepatitis B virus provide additional challenges, and access to ancillary medical and psychiatric services may be limited. Patients with co-occurring HCV infection, substance use, and psychiatric illness can complete interferon treatment with careful monitoring and aggressive intervention. Clinicians must integrate early interventions for psychiatric conditions and drug use into their treatment algorithm. Few programs or treatment models are designed to manage co-occurring substance use, psychiatric illness, and HCV infection and therapy. The National Institute on Drug Abuse convened a panel of experts to address the current status and the long-range needs through a 2-day workshop, Co-occurring Hepatitis C, Substance Abuse, and Psychiatric Illness: Addressing the Issues and Developing Integrated Models of Care. This conference report summarizes current data, medical management issues, and strategies discussed.

The utility of indirect predictors of hepatitis C viremia.

OBJECTIVE: Although the majority of injection drug users (IDUs) have been exposed to hepatitis C (HCV), only 60-85% remain chronically viremic and at risk for HCV-induced progressive liver damage or transmitting HCV to others. Access to direct viral testing to establish the presence or absence of viremia is limited due to its expense. This study of 500 current and former IDUs examines the utility of demographic and biochemical features as a means of indirectly predicting HCV viremia. METHODS: Retrospective chart and laboratory review. RESULTS: Overall, 409 (81.8%) were viremic at the time of presentation. HCV viremia did not correlate with the presence of active drug or alcohol use, drug of abuse, duration of drug use, or length of injecting career, but was more common in males and African-Americans. An elevated ALT, found in 36% of patients, was the best biochemical predictor: 95.6% of these patients were viremic. Other predictors of viremia included thrombocytopenia, hypoalbuminemia, elevated GGT, and total bilirubin level, with a stepwise increase in viremia seen as the number of abnormal biochemical predictors increased. The absence of HCV viremia was more difficult to predict. Viremia was found in 66.3% of those lacking all biochemical predictors and even in 43.8% of those in the lowest 10th percentile of ALT. CONCLUSION: Although indirect demographic and laboratory parameters may be used to help predict viremia in 40% of HCV-exposed IDUs, they are inadequate substitutes for direct viral testing and instead should be used only as an adjunct to education and referrals in high-risk patients.

Treating hepatitis C in methadone maintenance patients: an interim analysis.

OBJECTIVE: This study evaluates the safety, tolerability, and efficacy of interferon/ribavirin combination therapy in methadone maintenance (MM) patients with active hepatitis C (HCV). End-of-treatment results are presented as an interim analysis of efficacy. METHODS: Fifty eligible MM patients with active HCV and concomitant liver fibrosis were treated with interferon/ribavirin combination therapy using standard dosing regimens. Patients with active drug or alcohol use at the start of treatment, severe or untreated psychiatric illness, and/or decompensated liver disease were excluded. RESULTS: Treated MM patients were older, had a longer history of HCV infection, a high prevalence of psychiatric illness, and had substantially more liver fibrosis than in previous studies of HCV treatment in non-opioid-dependent populations. Seventy-eight percent completed the 6-12 month course of treatment. The end-of-treatment virologic response rate was 64% in patients completing treatment and 54% on an intent-to-treat basis. CONCLUSION: Methadone maintenance patients exhibit a number of factors that make HCV treatment more difficult: they are older, have a higher prevalence of psychiatric illness, and show evidence of more advanced liver disease. Despite this, their end-of-treatment response rate to interferon/ribavirin combination therapy is similar to that of patients without a history of IDU. Further analysis of the sustained virologic response (SVR) rate is planned at the study's completion. These preliminary results show that MM patients are in need of timely HCV diagnosis, and should be considered good candidates for referral and HCV treatment.