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Original Research |

Relationship Between Adherence to Hepatitis C Virus Therapy and Virologic Outcomes: A Cohort Study

Vincent Lo Re III, MD, MSCE; Valerie Teal, MS; A. Russell Localio, PhD; Valerianna K. Amorosa, MD; David E. Kaplan, MD, MSc; and Robert Gross, MD, MSCE
[+] Article and Author Information

From University of Pennsylvania School of Medicine and Philadelphia Veterans Affairs Medical Center, Philadelphia, Pennsylvania.


Presented in part at the 26th International Conference on Pharmacoepidemiology and Therapeutic Risk Management, Brighton, United Kingdom, 19–22 August 2010, and the International Conference on Viral Hepatitis 2011, Baltimore, Maryland, 11–12 April 2011.

Disclaimer: This material is based on work supported in part by the Department of Veterans Affairs. The contents do not represent the views of the Department of Veterans Affairs or the U.S. Government.

Grant Support: By grant K01 AI070001 from the National Institutes of Health (Dr. Lo Re), grant HS10399 from the Agency for Healthcare Research and Quality Centers for Education and Research on Therapeutics cooperative agreement (Drs. Lo Re, Localio, and Gross), and a Department of Veterans Affairs Competitive Pilot Project Fund grant (Drs. Lo Re and Amorosa).

Potential Conflicts of Interest: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M10-2805.

Reproducible Research Statement:Study protocol and statistical code: Available from Dr. Lo Re (e-mail, vincentl@mail.med.upenn.edu). Data set: Data in the National VA Hepatitis C Clinical Case Registry is available to VA researchers only and can be requested from the Department of Veterans Affairs.

Requests for Single Reprints: Vincent Lo Re III, MD, MSCE, Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania School of Medicine, 836 Blockley Hall, 423 Guardian Drive, Philadelphia, PA 19104-6021; e-mail, vincentl@mail.med.upenn.edu.

Current Author Addresses: Dr. Lo Re: Division of Infectious Diseases, Department of Medicine, Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania School of Medicine, 836 Blockley Hall, 423 Guardian Drive, Philadelphia, PA 19104.

Ms. Teal: Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania School of Medicine, 509C Blockley Hall, 423 Guardian Drive, Philadelphia, PA 19104.

Dr. Localio: Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania School of Medicine, 606 Blockley Hall, 423 Guardian Drive, Philadelphia, PA 19104.

Dr. Amorosa: Division of Infectious Diseases, Department of Medicine, Philadelphia VA Medical Center, Room A809, 3900 Woodland Avenue, Philadelphia, PA 19104.

Dr. Kaplan: Division of Gastroenterology, Department of Medicine, Philadelphia VA Medical Center, Gastroenterology Research, Room A402A, 3900 Woodland Avenue, Philadelphia, PA 19104.

Dr. Gross: Division of Infectious Diseases, Department of Medicine, Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania School of Medicine, 804 Blockley Hall, 423 Guardian Drive, Philadelphia, PA 19104.

Author Contributions: Conception and design: V. Lo Re, A.R. Localio, V.K. Amorosa, R. Gross.

Analysis and interpretation of the data: V. Lo Re, V. Teal, A.R. Localio, V.K. Amorosa, D.E. Kaplan, R. Gross.

Drafting of the article: V. Lo Re, A.R. Localio.

Critical revision of the article for important intellectual content: V. Lo Re, A.R. Localio, V.K. Amorosa, D.E. Kaplan, R. Gross.

Final approval of the article: V. Lo Re, V. Teal, A.R. Localio, V.K. Amorosa, D.E. Kaplan, R. Gross.

Statistical expertise: V. Lo Re, V. Teal, A.R. Localio.

Obtaining of funding: V. Lo Re, V.K. Amorosa, R. Gross.

Administrative, technical, or logistic support: V.K. Amorosa.

Collection and assembly of data: V. Lo Re, V. Teal.


Ann Intern Med. 2011;155(6):353-360. doi:10.7326/0003-4819-155-6-201109200-00003
Text Size: A A A

Background: Adherence to therapy with pegylated interferon and ribavirin for hepatitis C virus (HCV) infection has been incompletely examined.

Objective: To evaluate the relationship between adherence to HCV therapy and early and sustained virologic response, assess changes in adherence over time, and examine risk factors for nonadherence.

Design: Retrospective cohort study.

Setting: National Veterans Affairs Hepatitis C Clinical Case Registry.

Patients: 5706 HCV-infected patients (genotypes 1, 2, 3, or 4) with at least 1 prescription for both pegylated interferon and ribavirin between 2003 and 2006 and HCV RNA results before and after treatment initiation.

Measurements: Adherence was calculated over 12-week intervals by using pharmacy refill data. End points included early virologic response (decrease of ≥2 log10 HCV RNA at 12 weeks) and sustained virologic response (undetectable HCV RNA 24 weeks after the end of treatment).

Results: Early virologic response increased with higher levels of adherence to ribavirin therapy over the initial 12 weeks (patients with HCV genotype 1 or 4, 25 of 68 [37%] with ≤40% adherence vs. 1367 of 2187 [63%] with 91% to 100% adherence [P < 0.001]; patients with HCV genotype 2 or 3, 12 of 18 [67%] with ≤40% adherence vs. 651 of 713 [91%] with 91% to 100% adherence [P < 0.001]). Among patients with HCV genotype 1 or 4, sustained response increased with higher adherence to ribavirin therapy over the second, third, and fourth 12-week intervals. Results were similar for adherence to interferon therapy. Mean adherence to therapy with interferon and ribavirin decreased by 3.4 and 6.6 percentage points per 12-week interval, respectively (P for trend < 0.001 for each drug). Patients who received growth factors or thyroid medications during treatment had higher mean adherence to antiviral therapy.

Limitation: This was an observational study without standardized timing for outcome measurements.

Conclusion: Early and sustained virologic responses increased with higher levels of adherence to interferon and ribavirin therapy. Adherence to therapy with both antivirals decreased over time, but more so for ribavirin.

Primary Funding Source: National Institutes of Health, Agency for Healthcare Research and Quality, and Department of Veterans Affairs.

Figures

Grahic Jump Location
Figure 1.
Study flow diagram.

HCV = hepatitis C virus.

Grahic Jump Location
Grahic Jump Location
Figure 2.
Proportion of patients with early virologic response at each level of adherence to therapy with pegylated interferon and ribavirin over the initial 12 weeks, by HCV genotype.

HCV = hepatitis C virus.

Grahic Jump Location
Grahic Jump Location
Figure 3.
Proportion of patients with sustained virologic response at each level of adherence to therapy with pegylated interferon and ribavirin over later 12-week intervals for HCV genotypes 1 or 4 and genotypes 2 or 3.

HCV = hepatitis C virus.

Grahic Jump Location

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