Hepatitis C Harm Reduction Project

Keith Cylar, 1958-2004

Keith Cylar was a leader in the harm reduction movement and the fight against AIDS. A proud gay black man living with HIV, Keith was a co-founder and co-president of Housing Works, the largest provider of services to the homeless with AIDS and HIV in New York. Keith was funny, fierce, engaged, passionate, charismatic, controversial, smart, sweet, and seductive--very much alive, and dedicated to both seeking out the pleasures life offers and redressing the world's injustices. He epitomized "outspoken" and was a forceful advocate in New York and nationwide. I'll miss his support, laughter, courage, and inspiration; his death comes as a deep blow to so many people and to activism around AIDS, housing, and harm reduction everywhere.

Allan Clear, Executive Director of the Harm Reduction Coalition, wrote, "There will be lots said about Keith over the next few days. All of it will be true and he would have been proud of it. He was irrepressible, brilliant, arrogant, visionary, a leader, principled, always late, ahead of his time and so on. No-one can ever say that Keith didn't accomplish what he set out to do. His death is incredibly sad and it has choked me up all day to think about it. His death is all our loss."

Dennis deLeon of the Latino Commission on AIDS wrote "You had the sense after talking with Keith that no power structure was unbeatable. He played the inside game of politics very well and knew how to hit hard from the outside. And he made us laugh by always verbalizing what was on everybody’s mind. I watched him grow into a bridge-builder, coalition forger, and team player. I am sure he would shudder at this accolade."

Memorial Service Details

The wake will be held on Monday, April 12th from 6:00 PM - 9:00 PM at the Church of the Intercession at 550 West 155th Street between Broadway and Amsterdam Avenue, including a service from 7 to 8 PM.

The funeral will be held on Tuesday, April 13th at 12 Noon at the Church of the Intercession at 550 West 155th Street between Broadway and Amsterdam Avenue.

Following the funeral service, there will be a motorcade (including buses for those without vehicles) downtown and a procession to the Housing Works residence at 9th Street and Avenue D for internment of Keith’s ashes in the garden and a reception.

From 6:30 PM- 10:00 PM, Housing Works is -- as per Keith's insistence! -- hosting a party for Keith at Webster Hall, 125 East 11th Street, between 3rd and 4th Avenues.

Housing Works has established a Keith Cylar Fund in his memory. Donations may be sent to 320 W. 13th Street, 4th Floor, New York, NY 10012. Credit card donations are also accepted at the Housing Works website.

More on Keith:

Message from Housing Works

Gay City News story

New York Times obituary (see below for full text).

Interview with Keith (Microsoft Word document) by Ben Shepard, exerpted from From ACT UP to the WTO: Urban Protest and Community Building in the Era of Globalization (Shepard & Hayduk, eds., Verso 2002).

Generic Ribavirin Price Alert (UPDATED)

Generic versions of ribavirin finally received approval from the U.S. Food and Drugs Administration (FDA) this week. Both Three Rivers Pharmaceuticals (in partnership with Par Pharmaceutical, a subsidiary of Pharmaceutical Resources Inc. [PRI]) and Sandoz (formerly Geneva, a subsidiary of Novartis) can now market generic ribavirin—Three Rivers/Par calls their version Ribasphere, while Sandoz does not use a brand name (see PDFs of FDA approval letters for Three Rivers and Sandoz; also press releases from Three Rivers, PRI, Sandoz [PDF], Novartis). This marks the culmination of a three-year battle between generic manufacturers and brand-name companies, but any hopes for reducing the cost of hepatitis C treatment were dashed by the announced prices.

Hepatitis A and IDUs

When we think of viral hepatitis and injection drug users (IDUs), we usually think of hepatitis C. But hepatitis A also poses a significant threat to IDUs. Here's why:

Hepatitis A can be transmitted through blood, so sharing needles and injection equipment (cookers, cotton, water) could put IDUs at risk for hepatitis A

A study in Baltimore from the mid-1990s found that 66% of IDUs had been infected with hepatitis A (see PDF of article from Clinical Infectious Diseases). More recently a Vancouver study found evidence of past hepatitis A infection in 43% of IDUs (full text of article from Canadian Medical Association Journal; PDF here)

The Centers for Disease Control (CDC) reports that 5% of all new cases of hepatitis A in the United States occur among IDUs – but since half of all new cases have no reported risk, this figure may underestimate the rate of new infections in IDUs.

Hepatitis A is rarely fatal. But if you already have hepatitis C, getting hepatitis A can cause fatal liver failure (see abstract in New England Journal of Medicine).

The good news is that hepatitis A is almost totally preventable through vaccination. Injection drug users and people with hepatitis C should be vaccinated for hepatitis A.

Call for Increased CDC Funding for Hepatitis C

A coalition of hepatitis C advocates is asking organizations to sign on to their request to Congress to increase funding to the Centers for Disease Control (CDC) for hepatitis C. Funding would be used towards implementing the CDC National Hepatitis C Prevention Strategy and recommendations from the National Institutes of Health's 2002 Consensus Statement on the Management of Hepatitis C.

From the CDC's Executive Summary of the national prevention strategy:

"The goals of the National Hepatitis C Prevention Strategy are to lower the incidence of acute hepatitis C in the United States and reduce the disease burden from chronic HCV infection. Achievement of these goals requires: 1) harm reduction programs directed at persons at increased risk for infection to reduce the incidence of new HCV infections; 2) counseling, testing, and medical evaluation and management of infected persons to control HCV-related chronic liver disease; 3) surveillance to evaluate the effectiveness of prevention activities; and 4) research to provide answers to questions pertinent to the prevention and control of hepatitis C."

The full strategy, released in 2001, is available as a PDF file here.

Here's the message from hepatitis C advocates:

The National Hepatitis C Advocacy Council (NHCAC) needs your organizations support!

Below is a sign-on letter to show your support for the increased hepatitis C
appropriations requested by members of National Hepatitis C Advocacy
Council. NHCAC has delivered this letter to Senators and Congressmen
supporting the “Hepatitis C Epidemic Control and Prevention Act.”

WHO SHOULD RESPOND: Organizations serving people with, or at risk for,
hepatitis C (Please do not sign as individuals, if you are not a member of
an organization but are in support of the appropriation request and your
local group is not listed, call your local organization, make sure they are
in support of this and are signing on. Also, please register yourself and/or
your organization for our “Legislative Update” email action alert list at
the NHCAC website.)

WHEN SHOULD YOU RESPOND: Organizations wishing to sign on should e-mail by 5 pm EST, Wednesday, April 14, 2004.

WHERE SHOULD YOU RESPOND: Send emails to Lorren Sandt.

The “Hepatitis C Epidemic Control and Prevention Act” can be viewed here.

Please help distribute this letter and encourage organizations to sign-on.

Full text of the letter appears below.

Doctor-Patient Communication

A new study found that out of 322 people with hepatitis C receiving care at a midwestern hospital, 41% described communication problems with their doctors. Most frequently reported problems:

- poor communication skills of physicians (28%)
- physician incompetence regarding the diagnosis and treatment of HCV infection (23%)
- feelings of being misdiagnosed, misled, or abandoned (16%)
- being stigmatized by their physician (9%)

Communication problems were twice as likely with specialists (gastroenterologists or infectious disease doctors) than with general practitioners. People with emotional problems or weak social support were more likely to report communication problems. However, neither psychiatric illness nor current or former drug use were associated with experience of communication problems with doctors.

(Zickmund et al. Hepatitis C Virus-Infected Patients Report Communication Problems With Physicians. Hepatology 2004;39:999 –1007. Abstract here; NATAP has the text of the article here and an accompanying commentary also published in Hepatology by Robert Fontana and Ziad Kronfol here)

This study likely underestimates the extent of communication problems with doctors for current and former drug users with hepatitis C. Here's a sample of things that I've heard from people in a hepatitis C group I've been doing at a harm reduction program in the Bronx:

"My doctor said I had hepatitis, but I don't need to worry about it."
"My doctor said I had the good genotype, so I won't get side effects."
"They tested my blood and told me I was immune to hepatitis A and C."
"I was told that if I want to get hepatitis C treatment, I'll have to stop taking my HIV meds."
"He told me that my liver enzymes are normal, so I don't need hepatitis C treatment."

One last example -- in a recent group, a participant co-infected with HIV and hepatitis C told us that he'd recently started hepatitis C treatment with pegylated interferon and ribavirin. He'd been on hepatitis C treatment for a month, and went back to see his doctor to check in and get his prescriptions refilled. His regular doctor was away or unavailable, so he saw someone else, who gave him new prescriptions. When he got to the pharmacy, he saw that they'd given him a prescription for ribavirin but not interferon. He asked the pharmacist, who checked with the doctor and said that was right, just ribavirin. There's absolutely no medical reason for dropping interferon completely one month into therapy while keeping someone on ribavirin. The participant hadn't been told why interferon was being dropped or given any explanation.

Most of these examples would fall under the category of physician incompetence. But many drug users describe feeling stigmatized by doctors for their drug use -- past or present, real or imagined. For a painful account of the experiences of a drug user with HIV trying to navigate the medical system in New York, see One Junky's Odyssey from the fall 1997 issue of Harm Reduction Communication.

In an article in the Medical Journal of Australia, Lisa Waller describes her experience getting tested by her doctor for hepatitis C:

"In 2000, my doctor’s response to my request for an HCV test was 'you wouldn’t have that'. My subsequent admission of injecting drug use all those years ago was met with silence, but she ordered the test. When I went back for the results it seemed that she didn’t want to know about me or my illness, despite the fact that I was very sick. She offered almost no information at all about the virus, explaining that she 'just doesn’t see it' in her surgery, and handed me a brochure produced in 1991, which said there was little in the way of treatment, that the prognosis was not good, and that the highest risk group was homosexual men. All of this was simply untrue in 2000, but I did not know that then.

"I felt that my GP’s diagnosis was not that I had a serious liver disease, but an untreatable moral malady. If I had been one of the many people who are diagnosed before they experience any symptoms, I would have left her rooms, not told a soul and tried to forget all about it.

"I didn’t go home filled with righteous indignation and contempt for my doctor that day. I was consumed with self-loathing — I felt like a piece of human debris, unclean and totally unworthy."

from Living with hepatitis C: from self-loathing to advocacy. MJA 2004;180(6):293-294. The full text is available here (PDF version) and well worth reading. Related: Treloar et al. Hepatitis C-related discrimination in healthcare. MJA 2002;177(5):233-4. A report from the Third Australasian Conference on Hepatitis C, Melbourne, March 2002. Full text online, PDF version.

See also 'C-change: the report of the enquiry into hepatitis C related discrimination' released by Australia's Anti-Discrimination Board of New South Wales in November, 2001. The authors of this report found that "discrimination against people with hepatitis C is widespread and often motivated by fear and ignorance and is often based on the stigma associated with injecting drug use and associated stereotypes." Executive summary here; conclusions here. The main site links to PDF files of individual chapters, including recommendations; see also a 2-page PDF of the report summary.

See also another article by the group that conducted the study on physician communication -- Zickmund et al. "They treated me like a leper": Stigmatization and the quality of life of patients with hepatitis C. J Gen Intern Med. 2003;18(10):835-44. Abstract here -- "A total of 147 of the 257 study patients experienced stigmatization that they attributed to the disease. Women were more likely to report perceived stigmatization than men. Age, education, professional status, and mode of infection did not influence the likelihood of stigmatization. Stigmatization was associated with higher anxiety and depression, worsened quality of life, loss of control, and difficulty coping. Individuals who experienced stigmatization also mentioned problems in their health care and work environment as well as with family members."

Brian Edlin from the Center for the Study of Hepatitis C at Weill Medical College of Cornell University in New York compiled a list of "Principles for Managing Health Care Relationships with Substance-Using Patients":

· Establish a climate of mutual respect
· Maintain a professional approach that reflects the aim of enhancing patients’ well being; avoid creating an atmosphere of blame or judgment
· Educate patients about their medical status, proposed treatments, and their side effects
· Include patients in decision making
· If possible, establish a multidisciplinary team consisting of primary care physicians, HIV specialists, psychiatrists, social workers, and nurses
· Have a single primary care provider coordinate the care delivered by such a team to maximize consistency and continuity
· Define and agree on the roles and responsibilities of both the health care team and the patient
· Set appropriate limits and respond consistently to behavior that violates those limits
· Minimize barriers to participation (penalties for missed visits, and so forth)
· Recognize that patients must set their own goals for behavior change and work with patients to achieve commitment to realistic goals for healthier behaviors
· Acknowledge that abstinence is not always a realistic goal; emphasize risk reduction measures for patients who continue to use drugs
· Acknowledge that sustaining abstinence is difficult and that success may require several attempts
· Be familiar with local resources for the treatment of drug users
· Pitfalls to avoid:

Unrealistic expectations
Frustration
Anger
Moralizing
Blame
Withholding therapy

from Prevention And Treatment Of Hepatitis C In Injection Drug Users. Hepatology 2002;36(5 Suppl 1):S210-9. PDF available here.

Treatment for Non-Responders

Only about half of all people treated for hepatitis C with pegylated interferon and ribavirin achieve a sustained virologic response (SVR), defined as an undetectable hepatitis C viral load six months after the end of treatment. Among those who don't achieve an SVR, three patterns have been described:

- Relapsers: people whose viral load becomes undetectable during therapy, but later returns to detectable levels

- Partial responders: people who experience a significant drop in viral load during therapy, but never become undetectable

- Non-responders: people who never experience a meaningful drop in viral load during therapy

These three categories are often lumped together as "non-responders" despite differences between the groups. For example, people who respond at all to treatment -- relapsers and partial responders -- may experience some benefit from therapy, even without an SVR, in the form of an improvement in the condition of their liver (called a histologic response, generally marked by a reduction in liver inflammation). In theory, relapsers might benefit from a longer course of treatment, but extending treatment probably would not help non-responders.

Some people who did not achieve an SVR using earlier, less effective forms of treatment (standard interferon alone or with ribavirin, or pegylated interferon alone) may achieve an SVR using pegylated interferon in combination with ribavirin. One recent report described 604 "non-responders" to standard interferon (with or without ribavirin) who were retreated with pegylated interferon (Roche's Pegasys) and ribavirin (abstract here). Only 18% achieved an SVR. An SVR was more likely in people who had never taken ribavirin before, people who were able to stay on the full dose of ribavirin, and people who had hepatitis C genotype 2 or 3, which generally respond better to treatment. People with cirrhosis -- those in greatest need of successful treatment -- were less likely to achieve an SVR.

Another form of interferon, Infergen or consensus interferon, has been on the market for several years. Infergen is a synthetic form of interferon alpha, developed by Amgen and licensed to InterMune. Infergen is based on a consensus sequence of all interferon alpha subtypes -- hence the name "consensus interferon." Interferon alpha is a protein naturally produced in the body; our genes encode at least a dozen functional subtypes of interferon alpha -- variants of the protein with minor genetic differences. In contrast to Infergen, interferon alfa-2a (Roferon-A; Roche) and interferon alfa-2b (Intron A; Schering-Plough) are recombinant forms of interferon alpha based on a single subtype.

By some measures, Infergen demonstrates higher levels of antiviral activity than interferon alfa-2a and interferon alfa-2b in test tube studies. Studies of Infergen used as monotherapy for chronic HCV showed efficacy and tolerability comparable to or better than interferon alfa-2b . A preliminary analysis of a thrice-weekly regimen of Infergen in combination with daily ribavirin showed a sustained virologic response of 55%, compared with 31% among patients treated with standard interferon alfa-2b and ribavirin. In small, open-label studies, treatment with Infergen and ribavirin produced sustained virologic responses in some individuals who did not respond to or relapsed after prior interferon alfa treatment, suggesting a role as second-line therapy.

Infergen's use in clinical practice is minimal compared to Roche and Schering’s pegylated interferons. Use of Infergen was initially limited due to the superiority of combination therapy with interferon alpha and ribavirin. When originally approved, ribavirin was only available for use with Schering’s interferon alfa-2b (Intron A). Schering bundled ribavirin with Intron A, so that ribavirin was not sold separately to be combined with other interferons. While Schering now markets ribavirin separately, standard interferon has been supplanted by more effective pegylated forms that only need to be taken once a week. Infergen doesn't come in pegylated form, though InterMune initiated a pilot study of a pegylated version of Infergen in early 2003.

Yesterday, InterMune announced a new focus on researching and promoting the use of Infergen in non-responders. They'll start a large study of combination therapy with Infergen and ribavirin in the coming months. InterMune is also doing a smaller study of Infergen in combination with Actimmune, another InterMune drug that's a synthetic version of interferon gamma (an interferon protein with overlapping but distinctive antiviral effects). Finally, InterMune is working on developing protease inhibitors for hepatitis C, though none are in human studies yet.

If Infergen has an advantage, it's that some partial responders and non-responders to current treatment may get better results with Infergen. InterMune estimates that there are 150,000 non-responders to treatment in the United States, and that number is growing by 50,000 each year. Drawbacks with Infergen include the side effects common to all interferon treatment, and the fact that unless InterMune pursues further development of a pegylated form, Infergen requires injections three times a week.

InterMune would do well to target their research efforts to people most in need of effective treatment -- those with cirrhosis, people with genotype 1 (considered the hardest to treat), African-Americans and people with HIV (two groups with lower chances of achieving an SVR).

Related: see the follow-up post from May 10, 2004: Intermune and Infergen Interlude