Wednesday, December 5, 2012

CCO - Why I’m Starting to Use HCV Protease Inhibitors in Active Drug Users

Why I’m Starting to Use HCV Protease Inhibitors in Active Drug Users

Graham R. Foster, FRCP, PhD - 12/3/2012
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Injection-drug users have very high rates of infection with HCV, and in many developed countries, they act as the reservoir of infection with high rates of ongoing transmission.

Pioneers of HCV Treatment in IDUs
For many years, therapy for such patients was regarded as near impossible. It was generally agreed that the adverse effects and difficulties of interferon-based treatment regimens combined with the high risk of reinfection precluded effective treatment. However, a number of pioneers challenged this concept, and over the last few years, several groups in North America, Australia, and Europe have shown that, in carefully managed clinical settings, therapy for active injectors is both safe and effective.

Keys to Success
The key to success appears to be the use of a multidisciplinary team with outreach clinics close to the client group providing a range of services, including psychiatric and social support. In such settings, therapy is effective and long-term follow up data indicate that reinfection is uncommon. Recent modeling studies show that HCV therapy for injectors is cost-effective and may have a significant impact on the prevalence of disease.

Hope for the Same With PIs
Given the success of interferon and ribavirin in injectors, I have been considering whether or not to extend treatment to include protease inhibitors. My group, like many others, involves an nurse-led outreach service, and we have been treating active drug users for more than 5 years. With a pool of experienced nurses, a population of patients with advancing disease (a number of our patients now have end-stage liver disease), and a determination not to discriminate against any patient group, we believe that we should be offering protease inhibitors to active drug users.

Facing the Challenges
Clearly there are risks—although methadone does not interact with telaprevir and boceprevir, we have very limited data on street opiates, and there is the potential for significant drug–drug interactions that may cause harm. Our colleagues in Scotland are planning to overcome this by ensuring that patients receiving protease inhibitors have access to a “buddy” who is trained in naloxone administration; this approach seems very sensible and we await news of its success with interest. In addition to the problems of opiate overdose, there are fears that amphetamines may interact with protease inhibitors (in some settings amphetamine metabolism may be inhibited by protease inhibitors, leading to potentially lethal amphetamine overdose), and the effect of protease inhibitors on other stimulants, such as cocaine, is unclear.

We also have concerns about the tolerability of the protease inhibitor–associated anemia in vulnerable patients with unorthodox lifestyles. In addition, many drug users develop transient skin problems associated with contaminated drug use that may make identification of telaprevir-associated rashes challenging.
Nevertheless, on balance, we have decided that for patients with advanced disease the risk-to-benefit ratio is in favor of treatment, and we are about to initiate a small number of well-motivated patients on protease inhibitors. We plan to ask patients to stop using illicit drugs during the period of therapy, and we are restricting therapy in the first instance to patients who are well engaged in clinical services and have adequate social support.

Revisiting the Goals
I hope that if we are successful, we will be able to offer these effective new therapies to more of our vulnerable disadvantaged patients and, that by removing more infected injectors from the transmitter pool, we will be able to reduce the prevalence of infection. I am keen to ensure that my successors have less disease to treat, and clearing the “infected reservoir” seems a good way to start.

Your Thoughts?
What are your thoughts and experiences? Have you treated injection-drug users in the past? What were keys to your success? What challenges did you face? Have you or will you consider treatment with protease inhibitors in this population?

Topics: HCV - Treatment

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