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Is response guided therapy dead? Low cure rates in patients with detectable hepatitis C virus at week 4 of treatment

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Abstract

Background

Historically, chronic hepatitis C virus (HCV) treatment was response-guided. Clinical trials with sofosbuvir indicated on-treatment virologic response was not predictive of sustained virologic response (SVR) and hence response-guided therapy (RGT) was abandoned. The purpose of this study is to examine the association between on-treatment 4-week HCV RNA and SVR in patients treated in real-world practice.

Methods

The study is a retrospective analysis of consecutive patients started on treatment with a sofosbuvir-containing regimen, January 1, 2014 through August 20, 2014, for HCV genotype 1–6 infection. Patients were treated by HCV specialists at 6 centers in the Project ECHO (Extension for Community Healthcare Outcomes) HCV Collaborative or in the community by primary care clinicians mentored by HCV specialists through Project ECHO. Patients were included if they were over 18 years, had evidence of chronic HCV, and were started on a sofosbuvir-containing regimen. The aspartate aminotransferase:platelet ratio index (APRI) was used to estimate fibrosis. The main outcome measures were 4-week HCV RNA and SVR.

Results

Overall SVR was 82.5 %. At week 4, HCV RNA was detected in 27.4 % of patients. Stepwise multivariable logistic-regression analyses identified APRI > 1.0, male sex, genotype 3, and detectable on treatment 4-week HCV RNA as independent predictors of failure to achieve SVR.

Conclusions

In a real-world setting, a significant proportion of sofosbuvir treated patients have detectable on-treatment 4-week HCV RNA. Detectable on-treatment 4-week HCV RNA is associated with virologic failure. More data are needed to formulate guidance for RGT with newly available HCV therapies.

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Abbreviations

AASLD:

American Association for the Study of Liver Disease

AST:

Aspartate transaminase

APRI:

Aspartate transaminase platelet ratio index (APRI)

BMI:

Body mass index

C.I.:

Confidence interval

DAAs:

Direct acting antiviral agents

ECHO:

Extension for Community Healthcare Outcomes

FDA:

United States Food and Drug Administration

GT:

Genotype

HCV:

Hepatitis C virus

HCV RNA:

Hepatitis C virus ribonucleic acid

HCC:

Hepatocellular carcinoma

IAS-USA:

International Antiviral Society-USA

IDSA:

Infectious Disease Society of America

IFN:

Interferon

PEG:

Pegylated interferon

RBV:

Ribavirin

RGT:

Response-guided therapy

SD:

Standard deviation

SMV:

Simeprevir

SOF:

Sofosbuvir

SVR:

Sustained virologic response

UNMHSC:

University of New Mexico Health Sciences Center

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Authors and Affiliations

  1. Division of Infectious Diseases, Department of Internal Medicine, University of New Mexico Health Sciences Center, Albuquerque, NM, USA

    Karla Thornton

  2. College of Pharmacy-Department of Pharmacy Practice, Project ECHO, School of Medicine, University of New Mexico Health Sciences Center, Albuquerque, USA

    Paulina Deming

  3. Hepatology Center for Liver and Hepatobiliary Disease, St. Joseph’s Hospital and Medical Center, Phoenix, AZ, USA

    Richard A. Manch, Ann Moore, Anita Kohli & Robert Gish

  4. Division of Abdominal Transplantation, Baylor College of Medicine, Houston, TX, 77030, USA

    Norman L. Sussman & Saira Khaderi

  5. Division of Allergy and Infectious Diseases, University of Washington, Seattle, WA, USA

    John Scott

  6. Infectious Diseases, Cherokee Nation Health Services, Oklahoma, USA

    Jorge Mera

  7. Utah Department of Internal Medicine, Division of Gastroenterology, Hepatology and Nutrition, University of Utah, Salt Lake City, USA

    Terry Box

  8. Project ECHO, School of Medicine, University of New Mexico Health Sciences Center, Albuquerque, USA

    Clifford Qualls & Miranda Sedillo

  9. Division of Gastroenterology and Hepatology, Department of Internal Medicine, University of New Mexico Health Sciences Center, Albuquerque, USA

    Sanjeev Arora

Authors
  1. Karla Thornton
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  2. Paulina Deming
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  3. Richard A. Manch
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  4. Ann Moore
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  5. Anita Kohli
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  7. Norman L. Sussman
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  8. Saira Khaderi
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  10. Jorge Mera
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  14. Sanjeev Arora
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Corresponding author

Correspondence to Karla Thornton.

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Conflict of interest

Karla Thornton, MD, MPH No financial, personal or professional conflicts of interest to disclose. Paulina Deming, PharmD No financial, personal or professional conflicts of interest to disclose. Richard A. Manch, MD, FAASLD, FACP, FACG Speaker and/or consultant for Gilead, Janssen, and AbbVie. Ann Moore, FNP Speaker and/or consultant for Gilead, AbbVie, BMS, Merck Anita Kohli, MD, MS No financial, personal or professional conflicts of interest to disclose. Robert Gish, MD Research support from Bristol-Myers Squibb Company, Gilead, Merck, Benitec, AbbVie. Consultant a/o Advisor for Abbot, AbbVie, Arrowhead, Bayer AG, Bristol-Myers, Squibb Company, Contravir, Eiger, Enyo, Genentech, Gilead Sciences, Hoffmann-LaRocher Ltd., Hologic, Idenix, Intercept, Isis Pharmaceuticals, Janssen, MedImmune, Merck, NittoDenko, Onyx. Clinical Advisory Board for AbbVie, Merck, Arrowhead, Contravir, Novira, Intercept, Isis, Persidio, Eiger, Enyo, Janssen, Medimune. Chair of Clinical Advisory board for Arrowhead. Data safety monitoring board for Novira and Presidio. Consulting confidentiality agreements with Intercept (2010–2015), Contravir (2015–present), Genentech (2015–present), Tekmira (2011–2015), Janssen (2015–present), MedImmune (2015–present), Eiger (2015–present), Novira (2015–present), Presidio (2015–present). Speaker’s bureau for: Bayer, BMS, Gilead Sciences Inc., Salix/Valeant, AbbVie. Minor stock shareholder for Kinex, Synageva, RiboSciences, CoCrystal. Stock options for Arrowhead. Norman Sussman, MD, FAASLD Research for AbbVie, BMS, Merck, Gilead. Consulting for Merck, BMS. Speaker for AbbVie, Janssen, Gilead. Saira Khaderi, MD No financial, personal or professional conflicts of interest to disclose. John Scott, MD, MSc Advisory board for Gilead, BMS. Data safety monitoring board for Tacere Therapeutics. Funding for clinical trial from Merck. Jorge Mera, MD No financial, personal or professional conflicts of interest to disclose. Terry Box, MD Advisory board for AbbVie, Gilead, Janssen. Funding from AbbVie, Gilead, Conatus, BMS, Boehringer, Ingelheim, Ikaria, Cumberland, Sundise, Salix, Novartis, Genfit. Speaker for AbbVie, Gilead, Janssen, Salix. Clifford Qualls, PhD No financial, personal or professional conflicts of interest to disclose. Miranda Sedillo, MS No financial, personal or professional conflicts of interest to disclose. Sanjeev Arora, MD Funding for research grants: Gilead, Merck, AbbVie.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was not obtained because the study was retrospective and observational.

Writing assistance

There are no additional contributors to acknowledge outside the authors listed above.

Grant Support

This research project was not funded.

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Thornton, K., Deming, P., Manch, R.A. et al. Is response guided therapy dead? Low cure rates in patients with detectable hepatitis C virus at week 4 of treatment. Hepatol Int 10, 624–631 (2016). https://doi.org/10.1007/s12072-016-9725-6

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  • DOI: https://doi.org/10.1007/s12072-016-9725-6

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