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Report 4 from the NIDA HCV & Substance Abuse Conference
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Reported by Jules Levin
November 15, 2003
Washington, DC
This conference brought together researchers and treatment care providers from all over the world who are providing care and treatment for injection drug users and individuals on methadone maintenance programs for HCV. The care providers and doctors reported data from the programs they’ve established to show that current and former substance abusers can be successfully treated for HCV with peginterferon and ribavirin. Integrated care programs that address the numerous problems such individuals face can provide the setting where HCV can be successfully treated. Successful treatment for HCV in this population accomplishes several things: health care can successfully be provided to a challenging group of patients who are sick; HCV presents a public health policy problem to the US and Worldwide, and since injection drug users are the most prevalent source for transmission successful care and treatment addresses a public health policy need to prevent further transmissions; although stigmatimzed by society for using injection drugs, this population deserves health care just as others; in HIV, we have decided to treat injection drug users and in fact provide HAART to them, so we can and should do the same in HCV.
This report contains discussion of 2 programs, one in Rhode Island that provides direct observed therapy for interferon/ribavirin treatment to HCV/HIV coinfected injection drug users. The second study is in Germany and reports on a study of initiating HCV treatment in a detoxification ward for injection drugs users. In both settings, patients received comprehensive and integrated support services designed to meet their needs. Preliminary study results show that injection drug users can be treated successfully for HCV. Reports on this conference will continue.
Direct Obsered Therapy in Delivering Care to HIV/HCV Coinfected Drug Users and Marginalized Populations
Lynn Taylor, MD, from the Miriam Hospital at Brown University in Rhode Island reported on their response to the increased mortality and morbidity due to HCV among HIV+ individuals and the prevalence of addiction and psychiatric disorders among co-infected patients. Taylor and colleagues at their HIV clinic established an intervention to deliver care to this population of patients. Insights gained from using direct observed therapy (DOT) in providing HIV medications guided the development of a multi-disciplenary, community-based program. The program is incorporated into the HIV clinic. It includes education, assessment and treatment of drug dependence, individualized treatment plans, and peer support. Partnership with a community mental health agency provides coordinated psycjiatric care, counseling and case management. Pegylated interferon administration offers an opportunity for consideration and prompt treatment of side effects as well as monitoring and assistance with substance abuse and psychiatric symptoms. DOT permits for addressing adverse events before they become intolerable and this optimizes adherence and safety.
Taylor reported on the results so far seen in the first 50 patients they have provided care to in this program. The results demonstrated that this approach is successful and should be considered as a tool to provide care and as a model for public health policy in addressing the epidemic of HCV in substance abusers. Taylor recommends that observed, integrated treatment is an ideal way to extend HCV treatment to coinfected substance abusers.
Treating Injection Drug Users for HCV in Detoxification Ward: compliance and sustained responses seen: German experience
Markus Backmund, MD, reported on his experience in treating injection drug users for HCV in Hamburg, Germany. He has been conducting clinical research with injection drug users and HCV and other medical consequences of drug abuse since 1991. He reported HCV prevalence among IDUs is 62-95% in Europe. He reported an update on his published study (Hepatology vol 34, no 1, 2001, Backmund et al) of treating IDUs upon their entry into opiate detoxification programs. 50 patients received interferon or peginterferon plus ribavirin.
Because of the allegedly poor compliance of IDUs with treatment requirements and conditions and the risk for reinfection, hepatologists recommend treatment only if former IDUs have spent 6 to 12 months drug free. The aim of this study was to investigate whether opiate-dependent IDUs can be successfully treated with interferon. 50 in-patients were enrolled during detoxification treatment.
The hypothesis that IDUs with chronic HCV infection can be treated successfully with interferon alfa-2a or with a combined regimen of interferon alfa-2a and ribavirin was confirmed. Of the 50 patients 39 missed none of the interferon injections up to the end of treatment, regardless of whether “end of treatment” was because of drop out, termination of treatment due to nonresponse, or successful completion of treatment. Although 11 patients omitted between 3 and 45 of the interferon injections, 2 of them had a sustained response.
The first HCV treatment was started during the detoxification treatment. Even if patients relapsed by using drugs they were allowed to continue their HCV treatment, even if they injected heroin again. While in the detox ward various medical, education and support programs were provided to the patients, these are described below. Compliance with taking HCV treatment was good. 20% of patients remained drug free. 80% of patients had one or more drug relapses. Despite relapsing 24% of the relapsers showed a sustained viral response. Two patients indicated that the severity of the side effects led to drug relapse. Patients who relapsed but were received methadone maintenance treatment achieved a 53% SVR. Individuals who did not relapse had a 40% SVR. Response rates were better for patients who kept clinic appointments (45% vs 8%). Individuals who were employed had better response rates (67% vs 29% who were not employed).
ETR was reported as 48% in published study report in Hepatology, SVR was 36%. Sustained response was similar for the variables “treatment regimen,” “mean HCV RNA,” and “age.” In the “treatment regimen” 35% of patients were treated with interferon alfa-2a alone, compared with 38% of patients who were treated with interferon alfa-2a and ribavirin. “Mean HCV RNA” was low in 38% and high in 35%, and “age” was under 29 years in 37% (<29 years) compared with over 29 years in 35%. Forty-eight percent of patients with genotype 2 or 3, and 26% of patients with genotype 1a or 1b, had cleared HCV RNA 24 weeks after the end of treatment. Female patients had a sustained response more often than male patients (41% compared with 33%). After leaving inpatient detoxification treatment, 80% of patients had one or more drug relapses: 30% were admitted to a substitution maintenance program after relapse, with a sustained response in 53%. Patients who were predominantly treated in an inpatient abstinence program or were living drug free at home had a sustained response of 20% and 60%, respectively. Seventy-six percent of patients came to more than two thirds of all appointments. These patients were treated more successfully (45%) than patients who had attended less than 66.6% of the appointments (6%; P < .05).
Backmund recommends identifying and treatment for acute HCV in IDUs. During the 24 weeks after treatment, they were unable to detect any reinfection, even among patients who injected heroin during this period. Follow-up of 3.5 years was reported by Backmund, and at least 80% of patients have maintained sustained viral response. In this study Backmund did not find reinfection to be a problem. One person was reinfected but it the person was a health care worker and it appears they may have had an accidental needle stick. Further studies are needed to explore the risk for reinfection, but these results are encouraging. Backmund concluded that HCV-infected drug addicts with chronic HCV infection can be treated successfully with interferon alfa-2a and ribavirin if they are closely supervised by physicians specialized in both hepatology and addiction medicine.
Here are excerpts from Backmund’s published article in the journal Hepatology. For patients who are currently injecting illegal drugs or drinking excessive amounts of alcohol, HCV treatment with interferon alfa and ribavirin is still not recommended on the grounds that the compliance of the IDUs is poor and the risk of reinfection high if they continue to inject drugs.
However, to our knowledge the compliance of IDUs with hepatitis C treatment has not been investigated. For this reason we conducted the following prospective trial. We believe that treatment and care by a specialist in addiction medicine improves the patients' compliance considerably. Effective treatment of HCV in IDUs could greatly reduce the general population's risk of becoming infected. Exclusion criteria were pregnancy, unsafe contraception, severe depression, and seropositivity for human immunodeficiency virus. In all, 50 patients were enrolled.
Our detoxification unit is a physically separate ward of a large medical department within a general hospital. It is located in what was formerly the director's mansion within the hospital compound and has 15 beds for opiate addicts. The treatment strategies known in Germany as “qualified detoxification” consist of medication-supported detoxification (preferentially methadone), diagnosis and treatment of other diseases (hepatitis B and C, acquired immunodeficiency syndrome, pneumonia, etc.), psychotherapy and social therapy, and a transition to an abstinence phase after detoxification. The unit is supervised by 2 physicians, 1 psychologist, 6 social workers, and 6 nurses.
In the first 24 hours (regardless of the patient's preferred opiate, e.g., methadone, dihydrocodeine, or heroin), a methadone dose was prescribed in accordance with the clinical evaluation. The medication-supported detoxification enabled most patients to participate in the sociopsychotherapy part of the program starting on the day of admission. This therapy included 2 group sessions and 1 individual session each day. In addition, a “group information session” was held once a week by one of the doctors. The main topics here were how to prevent an overdose, how to administer first aid, and how to protect oneself from contagious diseases.
All patients were examined and treated during the study time by the same 3 physicians. All 3 are specialists in both hepatology and addiction medicine. The first HCV treatment was initiated during detoxification treatment. Patients were instructed about what they can do to minimize their risk of becoming infected or of transmitting infectious agents to others, e.g., by not sharing syringes or needles or any injection equipment, and by avoiding blood contact. Prior to treatment, the patients were asked to consider whether the interferon treatment and the use of needles might lead to drug craving and a relapse. All patients were quite certain that this would not become a problem. The length of the inpatient sojourn was determined in accordance with the severity of the withdrawal process. Two weeks before a patient was to be discharged, HCV treatment was initiated (6 injections). Patients were taught the injection technique. Of the 6 injections of interferon alfa-2a, two were performed by the patients themselves under a doctor's supervision. Interferon alfa-2a and ribavirin were prescribed by us or by patients' physicians.
When patients were discharged from the inpatient detoxification unit, they were either sent home, where they continued visiting the hospital weekly on an outpatient basis, or were transferred to a special clinic with an abstinence program. Patients who relapsed were offered replacement therapy with methadone or dihydrocodeine. They were allowed to continue their HCV treatment through any of these contingencies, even if they injected heroin again. After leaving the detoxification unit, patients were assessed weekly regarding their condition and progress by 1 of the 3 specialists either in an outpatient or inpatient setting (abstinence program). Criteria were whether they were (1) treated in an inpatient abstinence program, (2) living at home, (3) receiving methadone or dihydrocodeine in a maintenance program after having had a drug relapse, or (4) injecting heroin again. In addition, they were questioned as to how many interferon injections they had missed. It was also noted whether they appeared for the prearranged blood test every 12 weeks. Once each month they had the opportunity to participate in a session of dynamic-oriented psychotherapy.
Until October 1998, all patients were given interferon alfa-2a alone (old regimen) at a dose of 6 million units subcutaneously 3 times per week for 12 weeks. They were then tested for HCV RNA again. If they still tested positive for HCV RNA, we stopped the interferon alfa-2a treatment. Those who had become negative for HCV RNA received interferon alfa-2a at a dose of 3 million units 3 times per week for a further 36 weeks. Since October 1998, we have provided interferon alfa-2a plus ribavirin (1,000 mg or 1,200 mg per day according to body weight) for 24 or 48 weeks (new regimen). Patients with genotype 1 were given medication for 48 weeks and patients with genotype 2 or 3 for 24 weeks, in accordance with EASL recommendations.27 All patients were assessed for adverse reaction every 4 weeks and for efficacy (HCV RNA levels) every 12 weeks during treatment. After completion of treatment, patients were evaluated at weeks 12 and 24.
Between August 1997 and December 1998, 266 opiate-dependent patients were admitted to the detoxification unit. Twenty of them refused to provide a blood sample. Antibodies to HCV were discovered in 161 (65%) of the 246 remaining patients, 106 (43%) were HCV-RNA positive, and an additional human immunodeficiency virus infection was confirmed in 6 of these individuals. Fifty patients declined treatment of their hepatitis C infection. Fifty participants were enrolled in the study, 34 of whom had previously undergone inpatient detoxification. On average they were 32.5 years old (range, 19-48 years). The 50th end of follow-up was in May 2000. Average serum alanine aminotransferase was 3.1 (68.4 U/L) times higher than the upper limit of normal (22 U/L).
The 34 patients who entered the study before October 1998 were treated with interferon alfa-2a alone, whereas the 16 patients who entered after October 1998 received a combined regimen of interferon alfa-2a and ribavirin. The inpatient detoxification lasted on average 28 days. Eleven patients underwent inpatient treatment for 14 days or less, and 9 patients for more than 40 days.
Thirty-six percent also used cocaine on a weekly basis, and 62% met the current criteria of benzodiazepine dependency. Forty-four percent drank alcohol daily; of these, 26% met the current criteria for alcohol dependency. Sixty-five percent consumed no alcohol at all; 18% consumed between 20 g and 80 g of alcohol daily, 10% consumed 100 g daily, 4% 120 g, 4% 160 g, and 2% each drank 180 g, 200 g, 220 g, or 240 g.
Compliance was assessed by sustained response to therapy (loss of HCV RNA 24 weeks after the end of treatment).
After 12 weeks of treatment, 46% of patients tested negative for HCV RNA, 54% had discontinued treatment (10% because of side effects, 10% because of noncompliance, 34% because of testing positive for HCV RNA). Thirty-six percent of all patients had a sustained response.
We decided to terminate the therapy for 5 of the 50 patients (10%) because of the magnitude of side effects. One female patient suffered hair loss, 2 patients developed severe depression, 1 patient had pancreatitis, and another experienced a weight loss of 20%. Forty-six of the patients (92%) reported a flu-like syndrome after the first injection which, after the third injection, was no longer deemed so severe. Seven patients (14%) suffered hair loss. Five patients (10%) complained of light to moderately depressive moods. In 9 patients (18%), the flu-like syndrome persisted for more than 5 days. The ribavirin treatment for 2 patients (4%) had to be interrupted when hemoglobin levels fell to less than 8 g/L.
HCV RNA tests were carried out 12 weeks and 24 weeks after completion of treatment. The patients with sustained response after treatment ended missed only one HCV RNA test appointment (after 12 weeks). The drug status settings were also reexamined, and the days were recorded when patients had injected heroin intravenously. None of them became reinfected, although 10 of 18 patients (56%) had relapsed and injected heroin intravenously for periods ranging from a few days to a few weeks.
Nine of the 18 patients (50%) were generally living drug free during the subsequent period of observation, although 3 of them experienced an interim relapse, taking heroin for up to 4 weeks. Six patients remained completely drug free during this period. Seven of the 18 patients (39%) were treated with methadone, and 5 of these 7 had a relapse with heroin. Two of the 18 patients (11%) had injected heroin intravenously for 20 of the 24 weeks, after a brief initial “clean” period.
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