Evaluating & deconstructing barriers to HCV treatment for co-infected drug users

Statistically the article intends to break down the myths of IDUs and treatment adherence, a damaging myth which keeps many IDUs excluded from treatment therapies.

Background

Globally, an estimated 4 to 5 million persons are co-infected with HIV and the hepatitis C virus (HCV). [Ref 1] HCV is a common and significant co-morbidity of the HIV disease, particularly among current and former injection drug users (IDUs), who acquired both viruses from injection drug use (IDUs) with shared, unsterilized equipment (Table 1). HIV accelerates hepatitis C disease progression; the risk of developing cirrhosis is doubled, and the risk of liver decomposition is six times greater for HIV/HCV co-infected persons vs. those with HCV alone. [Ref 2] End-stage liver disease caused by HCV coinfection has become one of the leading causes of death among HIV-positive people in Europe and the United States. [Ref 3, 4]

Barriers to treating HCV in co-infected persons: eligibility criteria
Substance abuse and psychiatric illness are among the most common reasons for co-infected patients being excluded from HCV treatment as these are thought to be major barriers to treatment adherence and tolerance… An alternate view is that drug addiction and mental illness are often chronic and that waiting for these conditions to be cured or in remission before initiating treatment is unrealistic and places many patients, especially co-infected patients, at greater risk of HCV disease progression. [Ref 5]

Glenn J. Wagner and Gery W. Ryan

AIDS, 2005

Hepatitis C is treatable –regardless of HIV status– although very few co-infected people undergo HCV treatment. Studies have reported a high prevalence of potentially treatment limiting co-morbidites –drug and alcohol use, psychiatric disorders and other illnesses– among coinfected people. [Ref 6, 7] Fleming and colleagues have estimated that only a third of co-infected individuals in the United States are eligible for HCV treatment, based on their experience at an urban HIV clinic. [Ref 8]

Thompson and colleagues surveyed 52 clinicians on their perception of eligibility for HCV treatment in a group of 133 co-infected patients, the majority homeless. Only 21% (29/133) were considered candidates for HCV treatment. The remaining 94 individuals were considered ineligible for a mean 3.2 for the following reasons:

• Concerns about adherence

(50%),

• Treatment refusal (48.9%),

• Depression (43.6%),

• Active drug use (33%),

• Inability to assess severity of hepatitis (22.3%),

• Liver disease not serious enough to warrant treatment (21.3%),

• Alcohol intake (19.1%),

• Lack of efficacy of HCV treatment (10.6%),

• Medical contraindications (8.5%). [Ref 9]

Overly restrictive eligibility criteria have become a substantial barrier to HCV treatment for mono and coinfected persons. According to the 2002 National Institutes of Health Consensus Statement on Management of Hepatitis C (available on-line at: consensus.nih.gov/2002/2002HepatitisC2002116html.htm), treatment of active drug users should be considered on an individualized, case-by-case basis. Many clinicians choose not to treat individuals who are using drugs and/or alcohol, despite clinical indication, the patient’s desire to initiate HCV therapy, and the greater risk of HCV disease progression among co-infected persons. It is outrageous that HCV treatment is often withheld from the highest prevalence population without careful consideration of medical needs and patient willingness/readiness to initiate treatment.

Given the prevalence and severity of hepatitis C among HIV-positive persons, increasing access and uptake of HCV treatment among all co-infected persons is a priority. A more flexible approach to HCV treatment eligibility is warranted, such as that proposed by Mehta and colleagues, which characterizes contraindications as ”non-modifiable and modifiable“ (Figure 1). [Ref 10]

Treating HCV in multiply-diagnosed persons
HIV-infected IDUs with chronic HCV infection should be considered to be candidates for anti-HCV therapy, especially given their higher risk of progression to end-stage liver disease and the higher risk of liver toxicity after beginning antiretroviral therapy. [Ref 11]

Brian Edlin, et al Clinical Infectious Diseases 2005

In 2001, Lynn Taylor, M.D. and her colleagues opened a co-infection clinic at Rhode Island’s Miriam Hospital Immunology Center (a Ryan White Comprehensive AIDS Resources-funded HIV clinic). Treatment for HIV and HCV is coordinated with psychiatry, addiction treatment and case management services. Persons with psychiatric disorders (including suicide attempts) are evaluated for HCV treatment based on their current stability; psychiatric care and medication are available for those who need them. The requirements for HCV treatment eligibility (in the absence of medical contraindications) are that patients ”…reasonably adhere to medical appointments and be willing to undergo psychiatric evaluation and engage in a psychiatric care plan as part of treatment for HCV infection.“

Each patient is offered individual and group educational sessions about the liver; hepatitis A and B; hepatitis C transmission, prevention, and natural history; alcohol and HCV progression; reducing or eliminating alcohol consumption; the evaluation process for HCV treatment; risks and benefits of HCV treatment, and adherence. Although liver biopsy is not a prerequisite for HCV therapy, a majority of patients have undergone the procedure.

The co-infection clinic has treated 17 people, and another 17 are preparing to initiate treatment. During treatment, side effects are monitored and promptly managed by a nurse, who administers pegylated interferon injections during weekly clinic visits. A case manager, who makes regular home visits, also follows patients. Although 100% of patients undergoing HCV treatment have a history of drug use, and 94% have been diagnosed with a psychiatric disorder, none have discontinued treatment because of drug use, relapse, or serious psychiatric problems,and the adherence rate for weekly clinic visits is 99%. [Ref 12]

In HCV monoinfection, a growing body of data indicates that drug and/or alcohol users and persons with psychiatric illnesses can be safely and effectively treated for hepatitis C. In one study, sustained virological response rates among persons in a methadone maintenance program did not differ significantly between persons on methadone vs. those using methadone and illicit drugs and/or alcohol during treatment. [Ref 13] Schaefer and colleagues studied adherence, side effects and HCV treatment outcomes among 81 people (16 with psychiatric disorders, 21 on methadone maintenance, 21 former drug users, and 23 controls [no history of drug use or psychiatric disorders]) treated with standard interferon plus ribavirin. A pre-treatment psychiatric evaluation and ongoing mental health care were provided during HCV treatment. The incidence and degree of interferon-induced depression did not differ significantly between groups; overall, 4 to 6 percent reported suicidal thoughts, which were addressed during psychiatric care. Although persons with psychiatric disorders were significantly more likely to have used antidepressants prior to, and during treatment, none discontinued treatment due to psychiatric side effects. Preexisting depression did not affect either discontinuation or response rates. The overall sustained virological response rate was 37% (methadone group, 43%; psychiatric disorders group, 38%; controls, 35%; former drug users, 28%). [Ref 14]

Re-infection and relapse
Clinicians often cite concerns about HCV reinfection and/or relapse to active drug use during treatment as rationale to withhold HCV therapy from current and former drug users. Reports of reinfection after completion of HCV therapy are rare. [Ref 15, 16] Concerns about reinfection can be addressed by counseling injection drug users about the risk for reinfection, demonstrating safer injection technique, and referring to syringe exchange and/or prescribing syringes. The side effects of interferon are similar to those of opiate withdrawal, and it is administered by injection. Cravings and relapse to drug use during treatment have been reported among former drug users. [Ref 13, 17, 18] Clinicians have a variety of interventions to offer patients who do not want to resume illicit drug use: referrals to 12-step programs, counseling, drug treatment programs, or substitution therapy with methadone or buprenorhpine. For persons who are on methadone maintenance, some clinicians have reported that increasing the methadone dose during HCV therapy lessen cravings and side effects of HCV treatment. [Ref 18, 19]

HCV treatment and alcohol: challenging the status quo
Heavy alcohol consumption is usually regarded as an absolute contraindication for HCV treatment, since it is believed to reduce treatment efficacy. The evidence for withholding treatment until a six-month period of abstinence from alcohol is weak, consisting of studies using standard interferon monotherapy, in which treatment adherence was not assessed. [Ref 20-23]

A more recent study, using standard interferon plus ribavirin, reported that alcohol use during HCV treatment did not affect SVR rates. [Ref 14] Unfortunately,clinical trials have excluded people who drink, so there is no data available on treatment outcomes among drinkers treated with newer, more effective anti-HCV therapies. Clearly, persons with HCV should be offered information and counseling on reducing or eliminating alcohol intake, and, if appropriate, pharmacotherapy with acamprosate or naltrexone. Although many clinicians only treat persons who have been abstinent from alcohol intake for three to six months, a few treat on a case-by-case basis [Ref 12, 13].

Since alcohol accelerates HCV progression, drinkers are at greater risk for serious liver disease than nondrinkers, and thus, should be considered for HCV therapy.

Education for providers
Providers constitute another barrier for the provision of care for IDUs coinfected with HCV and HIV because of insufficient training.

... As with other chronic medical conditions, providers need education about substance abuse and injection drug use as a disease. [Ref 24]

Thomas F. Kresina, et al Clinical Infectious Diseases, 2005

Surveys have found that clinicians are often uncomfortable treating patients who are dependant on drugs and/or alcohol, due to inadequate training. [Ref 25, 26] A 1996 survey of 66 accredited medical schools in the United States reported that 41% (28/66) did not include education on addiction. [Ref 26] Educating medical providers about drug and alcohol dependence increases their capacity and willingness to care for persons with drug and/or alcohol problems; medical students and physicians have reported increased confidence about their capacity to care for patients with drug and/or alcohol problems after brief, intensive training. [Ref 27, 28]

Adherence
Fears about adherence have often been cited as a concern or rationale for withholding treatment from active drug users, although physicians are notoriously poor predictors of adherence among their patients. [Ref 29-31] Many studies have reported that active drug use is associated with poor adherence to antiretroviral therapy [Ref 32-34], but some have not found a significant difference in adherence to antiretroviral therapy in drug users vs. non-users. [Ref 35, 36] Adherence to antiretroviral therapy among active drug users has been improved by several interventions: prescribing buprenophine [Ref 37], offering antiretroviral therapy at syringe exchange and methadone maintenance programs [Ref 38, 39], and by providing psychiatric care and antidepressants. [Ref 40]

Conclusion
Offering therapy for HCV to patients with substance use disorders should be viewed as a challenge, not an impossibility. [Ref 12]

Lynn E. Taylor, MD

Clinical Infectious Diseases 2005

HIV and HCV therapy have been successfully delivered to active drug users and persons with psychiatric disorders. Methods to improve adherence among persons with multiple diagnoses have been characterized. HCV treatment is a priority among co-infected persons, and access should be broadened. However, increasing access to HCV treatment is insufficient without addressing quality of care. All co-infected people must receive adequate information about risks and benefits of HCV treatment, optimal management of side effects, mental heath care, and peer support.

Tracy Swan

References
Full list to be published soon

EATN - European AIDS Treatment News, Volume 15, I – Spring 2006

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