HTTP/1.0 200 OK Content-Type: text/html Former Addicts Face Barriers To Treatment For HCV
Pubdate: Tue, 27 Feb 2001
Source: Journal of the American Medical Association (US)
Copyright: 2001 American Medical Association.
Section: Medical News and Perspectives
Vol. 285, No. 8, February 28, 2001
Contact:  515 N State St, Chicago, IL 60610
Fax: 312-464-4445
Author: Joan Stephenson, PhD
Bookmark: (Hepatitis)


Most injection drug users, including those who succeed in kicking the 
habit, are left with a worrisome legacy: infection with hepatitis C virus 
(HCV). But for a variety of reasons, some former addicts who develop 
HCV-related liver disease -- notably those receiving methadone maintenance 
therapy (MMT) -- are confronted with barriers to getting much-needed 
treatment for their illness, barriers that sometimes force them to choose 
between dying of liver disease and risking relapse and a return to abusing 

The problem is not a trivial one. More than any other group of individuals 
in the United States, injection drug users are likely to acquire the 
infection. According to the National Center for Infectious Diseases, half 
or more of all HCV infections are associated with illegal drug use and 
injection drug users typically become infected with stunning swiftness.

Despite the HCV burden in this group, physicians say that patients 
receiving MMT including individuals who haven't injected drugs for many 
years are all too frequently turned away for medical treatment for HCV or 
liver transplantation for HCV-related end-stage liver disease, excluded 
solely because of their medically approved use of methadone.

There are some legitimate concerns about the potential adverse effects of 
drugs used to treat hepatitis C for patients receiving MMT including a 
possible risk of relapse to active drug abuse. But experts agree that these 
concerns do not mean that patients taking the opioid agonist should be 
denied access to potentially life-saving HCV treatment.


J. Thomas Payte, MD, a San Antonio, Tex, physician in private practice who 
has treated people with opioid addiction since the early 1960s, noted that 
many of his MMT patients who have turned their lives around -- evidenced by 
years of psychosocial stability, steady employment, and complete abstinence 
from illegal drugs or alcohol -- are discriminated against when they seek 
drug treatment for HCV or a liver transplant.

He described the plight of one of his patients, a 46-year-old Arizona man 
with HCV who, after becoming a heroin addict at 17, had been stably 
maintained with methadone for more than 25 years. This man was on a waiting 
list for a liver transplant by 1996, but when a move to Texas forced him to 
seek placement on a transplant list in the San Antonio area, he was told he 
would not be considered until he had withdrawn from methadone. He died the 
following year.

Even though methadone treatment had served as a safe and effective 
long-term treatment for his opioid addiction, "he was expected to suffer 
and destabilize the addictive disorder to qualify for treatment of another 
disorder," Payte testified at a forum held by the United Network for Organ 
Sharing last September.

Payte noted that some of his patients have "made very difficult attempts" 
to withdraw from methadone when they were already ill with their liver 
disease. "Going through this protracted withdrawal process they almost 
decide they'd rather die of the disease than have to go through that in 
order to get treatment," Payte said.

Catherine Baca, MD, a physician at the University of New Mexico Health 
Sciences Center in Albuquerque who treats patients with substance abuse 
problems, has seen similar resistance by transplant centers with respect to 
accepting people receiving methadone therapy.

"I had to call a half-dozen centers for a patient who was denied care 
before I found one that was willing to accept him," she said.

A number of studies have shown that advising patients to stop methadone 
therapy puts them at high risk for relapse, said Baca. "Yet that's exactly 
what some people are requiring."

One barrier to gaining access to treatment is the stigma associated with 
addiction and with MMT, said Payte. The cost of the drugs is another 
obstacle. Many patients receiving methadone therapy don't have private 
health insurance or the financial resources to pay for costly HCV regimens, 
which include alfa interferon monotherapy, combination therapy with alfa 
interferon and ribavirin, or pegylated interferon (alfa interferon linked 
to a polyethylene glycol molecule, approved last month by the US Food and 
Drug Administration [FDA] for treatment of HCV).

Yet another avenue for gaining access to treatmentclinical trialsis often 
barred to patients taking the opioid agonist, Baca noted. The reason: the 
pharmaceutical companies sponsoring the trials list methadone as an 
exclusionary criterion.


It's not just stigma and financial constraints that are hindering 
methadone-taking patients' access to treatment, but a too-broad 
interpretation of hepatitis C treatment guidelines that arose from a 1997 
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) 
consensus conference. Among other things, the guidelines originally 
recommended a 2-year period of abstinence by heavy alcohol users and users 
of illicit drugs before they could be considered for HCV treatment, said 
Allan Rosenfield, MD, dean of Columbia University's Mailman School of 
Public Health.

Some clinicians apparently perceived the guidelines "to also exclude those 
individuals who are receiving methadone maintenance," said Steffanie 
Strathdee, PhD, an epidemiologist at Johns Hopkins School of Public Health, 
who has studied a group of injection drug users with HCV. In other cases, 
physicians who had participated in clinical trials that cited methadone use 
as an exclusion may have carried that thinking forward without any formal 
justification when the drugs were approved and being used in the clinic.

Rosenfield, who also heads the New York State AIDS Advisory Council, was 
among those who worked to persuade the NIDDK to revise these 
recommendations. "This Council concluded that the objections to treating 
active or recently active users of illicit substances are not supported by 
the medical literature," he said in a letter to the National Institutes of 

The now-revised NIDDK guidelines 
( state 
that current substance abuse or alcohol abuse is a contraindication to alfa 
interferon therapy. Continued alcohol consumption can increase liver 
damage, and there is concern that people who continue to inject drugs risk 
reinfection with multiple genotypes of HCV, which hepatologists worry may 
make treatment more difficult. The document also recommends a 6-month 
abstinence period before starting treatment, noting that interferon can be 
associated with relapse in individuals with a history of drug or alcohol abuse.

Now, however, the modified guidelines also explicitly note that "patients 
can be successfully treated while on methadone."


But there remain some important unresolved concerns about the safety of 
hepatitis C therapy for former injection drug users, including those 
receiving MMT, cautions William D. Schwieterman, MD, of the FDA's Center 
for Biologics.

"There are reasons why the agency has some concerns about the safety of 
interferon in this population," explained Schwieterman, drawing attention 
to a warning on the label of newly approved pegylated interferon. This 
product requires only one weekly injection, compared with thrice-weekly 
injections for other interferons. It also appears to be as effective as the 
interferon-ribavirin combination which until now had been the most 
successful HCV treatment and is expected to see wide use.

The label warns of the drug's potential for causing adverse 
neuropsychiatric events, including the possibility that patients with a 
history of drug abuse will relapse after starting the interferon regimen. 
During clinical trials, investigators observed relapses, drug overdoses, 
and deaths in such patients, including individuals who were receiving MMT.

All of the interferons warn about the potential for neuropsychiatric 
adverse events, including depression and suicide. But there's some 
suggestion that former drug users receiving pegylated interferon may be 
more prone to such events, as well as a return to injection drug use.

"But it's just too soon to tell with any certainty whether the pegylated 
interferons are going to prove more toxic in this regard," said 
Schwieterman. Nor is it known what the mechanism might be for this kind of 

The FDA has asked the drug's manufacturerKenilworth, NJ-based 
Schering-Plough Corpto conduct a phase 4 postmarketing study to examine the 
catabolism of methadone in patients receiving the drug, he noted. "We think 
it's an important enough question that it ought to be addressed directly."

Some people have also raised concerns about risks related to exposing 
former injection drug users to a long-term therapy that requires 
subcutaneous needle exposure, Schwieterman said. The possibility that such 
behavioral associations may play a role in fostering relapse "is something 
that needs to be considered," he said. "It's a very complicated issue."

Thus, while MMT is not a contraindication for patients seeking drug 
treatment for HCV, it's very important that clinicians be aware of the 
particular concerns about the drugs' safety for this group of patients, 
said Schwieterman. "For each patient, the physician has to consider the 
anticipated potential benefits versus the anticipated potential risks," he 

Whether unforeseen problems will indeed emerge when greater numbers of 
patients on methadone undergo drug treatment for HCV remains to be seen, 
said Leonard B. Seeff, MD, a hepatitis C researcher with the NIDDK. "The 
proof is in the pudding we're going to have to find out as we go along 
whether this course has problems."

Since limiting such risks will require careful monitoring of patients 
receiving hepatitis C regimens, MMT with its requirement for daily visits 
to a clinic may provide the means to help keep patients on track and to 
reach a population with an enormous HCV burden, said Strathdee. The 
epidemiologist, with David L. Thomas, MD, and other Hopkins colleagues, has 
been examining the natural history of HIV, HCV, and other infections in a 
group of people with a history of injection drug use.

"We found that if HIV-positive drug users were enrolled in treatment for 
their drug abusewhich is most often methadone maintenance they were more 
likely to be receiving HIV therapy," said Strathdee. "The two go hand in 
hand when they start to get their drug use under control, they start to 
feel they can take charge of their lives and make other healthy choices."
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