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Disclaimer: CME certification for these activities has expired. All information is pertinent to the timeframe in which it was released.


Advances In The Management Of HIV/HCV Coinfection


GOAL
To provide hepatologists, gastroenterologists, and infectious disease physicians with up-to-date information on the diagnosis and treatment of patients coinfected with human immunodeficiency virus/hepatitis C virus (HIV/HCV).

TARGET AUDIENCE
This activity is designed for hepatologists, gastroenterologists, and infectious disease physicians. No prerequisites required.

LEARNING OBJECTIVES
The Johns Hopkins University School of Medicine takes responsibility for the content, quality, and scientific integrity of this CME activity. At the conclusion of this activity, participants should be able to:

  • Describe the magnitude of the HIV/HCV coinfection problem in the United States.
  • Identify the diagnostic and clinical characteristics of patients who are coinfected with HIV and HCV.
  • Assess the data from recently reported large-scale controlled clinical trial results of therapy in patients with HIV/HCV coinfection (ACTG 5071, APRICOT, and RIBAVIC).
  • Evaluate the clinical implications of using combination pegylated interferon plus ribavirin therapy in patients with HIV/HCV coinfection.

ACCREDITATION STATEMENT
The Johns Hopkins University School of Medicine is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.

CREDIT DESIGNATION STATEMENT
The Johns Hopkins University School of Medicine designates this educational activity for a maximum of 1.75 category 1 credits toward the AMA Physician's Recognition Award. Each physician should claim only those credits that he/she actually spent in the activity.

The estimated time to complete this educational activity:  1.75 hours.

Release date: April 15, 2005. Expiration date: April 15, 2007.

DISCLAIMER STATEMENT
The opinions and recommendations expressed by faculty and other experts whose input is included in this program are their own. This enduring material is produced for educational purposes only. Use of Johns Hopkins University School of Medicine name implies review of educational format, design, and approach. Please review the complete prescribing information of specific drugs or combinations of drugs, including indications, contraindications, warnings, and adverse effects, before administering pharmacologic therapy to patients.

This program is supported by an educational grant from Roche Laboratories.

Full Disclosure Policy Affecting CME Activities:
As a provider accredited by the Accreditation Council for Continuing Medical Education (ACCME), it is the policy of Johns Hopkins University School of Medicine to require the disclosure of the existence of any significant financial interest or any other relationship a faculty member or a sponsor has with the manufacturer(s) of any commercial product(s) discussed in an educational presentation. The Program Director and Participating Faculty reported the following:

PROGRAM DIRECTOR

David L. Thomas, MD, MPH
Professor of Medicine
Department of Infectious Diseases
Johns Hopkins University School of Medicine
Baltimore, Maryland
Dr Thomas reports serving as a consultant for Bristol-Myers Squibb Company, Chiron Corporation, Idenix Pharmaceuticals Inc, and Roche Laboratories.

PARTICIPATING FACULTY

Raymond T. Chung, MD
Assistant Professor of Medicine
Harvard Medical School
Director of Hepatology
Medical Director
Liver Transplant Program
Massachusetts General Hospital
Boston, Massachusetts
Dr Chung reports receiving grants/research support from Roche Laboratories and Schering-Plough Corporation.

Douglas T. Dieterich, MD
Vice Chair and Chief Medical Officer
Department of Medicine
Mt Sinai School of Medicine
New York, New York
Dr Dieterich reports receiving grants/research support from Abbott Laboratories, Gilead Sciences, GlaxoSmithKline, Roche Laboratories, and Schering-Plough Corporation; and serving as a consultant for Abbott Laboratories, Gilead Sciences, GlaxoSmithKline, Roche Laboratories, and Schering-Plough Corporation.

Kenneth E. Sherman, MD, PhD
Gould Professor of Medicine
Director, Division of Digestive Diseases
University of Cincinnati College of  Medicine
Cincinnati, Ohio
Dr Sherman reports receiving grants/research support from Intermune Inc, Roche Laboratories, Schering-Plough Corporation, and SciClone Pharmaceuticals Inc; and serving as a consultant for Roche Laboratories, Schering-Plough Corporation, and SciClone Pharmaceuticals Inc.

Notice: The audience is advised that articles in this CME activity may contain reference(s) to unlabeled or unapproved uses of drugs or devices.

Dr Chung—pegasys and ribavirin in HIV/HCV coinfection.
Dr Sherman—pegylated interferon and ribavirin in HIV/HCV coinfection.

All other faculty have indicated that they have not referenced unlabeled/unapproved uses of drugs or devices.

Advanced Studies in Medicine provides disclosure information from contributing authors, lead presenters, and participating faculty. Advanced Studies in Medicine does not provide disclosure information from authors of abstracts and poster presentations. The reader shall be advised that these contributors may or may not maintain financial relationships with pharmaceutical companies.

Advances In The Management Of HIV/HCV Coinfection
By David L. Thomas, MD, MPH*

Over the past decade, the treatment of human immunodeficiency virus (HIV) infection has improved dramatically with the introduction of highly active antiretroviral therapy. As a consequence, morbidity and mortality caused by AIDS have decreased, and HIV-infected individuals are experiencing prolonged life expectancy. However, this unparalleled success has been accompanied by the emergence of hepatitis C-related liver disease as an important cause of morbidity and death in patients infected with HIV.

Coinfection with hepatitis C virus (HCV) in HIV-infected patients has been reported in 10% to 90% of patients, depending on the mode of acquisition of both viruses. The incidence of complications arising from hepatitis C-associated liver disease in coinfected patients is increasing exponentially and represents a significant challenge for patients and clinicians. The interaction of HIV and HCV is complex. It is clear that HIV infection negatively affects the natural history of HCV infection, whereas HIV-directed therapy may exacerbate hepatocellular injury induced by hepatitis C.

Despite advances in the medical management of HCV infection for monoinfected individuals, the management of hepatitis C in the HIV-infected person is complicated not only by differing epidemiologic characteristics and natural history but also by other issues, such as reduced HCV antibody production, drug interactions, and lack of experience with HCV therapy in HIV-infected individuals. Additional barriers to successful management of HCV infection include active psychiatric illness and drug or alcohol use among patients coinfected with HIV/HCV.

Introduction of pegylated interferon a (PEG-IFN a) in combination with ribavirin has dramatically improved the treatment of HCV infection, yielding sustained virologic response rates of 54% to 63% in monoinfected patients.1-3 Recent large, randomized trials of PEG-IFN a and ribavirin have demonstrated superior efficacy, with sustained virologic response rates of up to 40% and favorable risk-to-benefit ratios, in comparison with standard regimens of IFN plus ribavirin in patients coinfected with HIV/HCV.4-7 However, many questions still remain regarding appropriate strategies for optimizing HCV treatment in HIV-infected patients.

This issue of Advanced Studies in Medicine reviews the current understanding of the pathobiology and inter-relationship between HCV and HIV infection in co-infected patients. It presents an overview of the data from 3 recently completed randomized studies comparing the safety and efficacy of PEG-IFN a plus ribavirin therapy versus standard IFN plus ribavirin therapy for the treatment of patients coinfected with HIV/HCV. The monograph concludes with a discussion of special considerations in the management of HIV/HCV co-infection, specifically with respect to diagnosis, patient selection, and the timing of HCV therapy.

REFERENCES
1. Manns MP, McHutchison JG, Gordon SC, et al. PEG-interferon alfa-2b plus ribavirin compared with interferon alfa-2b plus ribavirin for initial treatment of chronic hepatitis C:
a randomised trial. Lancet. 2001;358:958-965.
2. Fried MW, Shiffman ML, Reddy KR, et al. PEG-interferon alfa-2a plus ribavirin for chronic hepatitis C virus infection. N Engl J Med. 2002;347:975-982.
3. Hadziyannis SJ, Sette H Jr, Morgan TR, et al. PEG-interferon-alfa2a and ribavirin combination therapy in chronic hepatitis C: a randomized study of treatment duration and ribavirin dose. Ann Intern Med. 2004;140:346-355.
4. Carrat F, Bani-Sadr F, Pol S, et al. Pegylated interferon alfa-2b vs standard interferon alfa-2b plus ribavirin for chronic hepatitis C in HIV-infected patients: a randomized controlled trial. JAMA. 2004;292:2839-2848.
5. Chung RT, Andersen J, Volberding P, et al. PEG-interferon alfa-2a plus ribavirin versus interferon alfa-2a plus ribavirin for chronic hepatitis C in HIV-coinfected persons. N Engl J Med. 2004;351:451-459.
6. Laguno M, Murillas J, Blanco JL, et al. PEG-interferon alfa-2b plus ribavirin compared with interferon alfa-2b plus ribavirin for treatment of HIV/HCV co-infected patients. AIDS. 2004;18:F27-F36.
7. Torriani FJ, Rodriguez-Torres M, Rockstroh JK, et al. PEG-interferon alfa-2a plus ribavirin for chronic hepatitis C virus infection in HIV-infected patients. N Engl J Med. 2004; 351:438-450.

*Professor of Medicine, Department of Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, Maryland.
Address correspondence to: David L. Thomas, MD, MPH, Professor of Medicine, Department of Infectious Diseases, Johns Hopkins University School of Medicine, 424 Bond Street, Baltimore, MD 21231. E-mail:
dthomas@jhmi.edu.





Johns Hopkins Advanced Studies in Medicine (ISSN-1558-0334), is published by Galen Publishing, LLC, d/b/a ASiM, PO Box 340, Somerville, NJ 08876. (908) 253-9001. Copyright ©2012 by Galen Publishing. All rights reserved. No part of this publication may be reproduced or transmitted in any form or by any means, electronic or mechanical, without first obtaining permission from the publisher. ASiM is a registered trademark of The Healthcare Media Group, LLC.