Is response guided therapy dead? Low cure rates in patients with detectable hepatitis C virus at week 4 of treatment.
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.
Division of Infectious Diseases, Department of Internal Medicine, University of New Mexico Health Sciences Center, Albuquerque, NM, USA. kthornton@salud.unm.edu.
Karla
K
Thornton
College of Pharmacy-Department of Pharmacy Practice, Project ECHO, School of Medicine, University of New Mexico Health Sciences Center, Albuquerque, USA.
Paulina
P
Deming
Hepatology Center for Liver and Hepatobiliary Disease, St. Joseph's Hospital and Medical Center, Phoenix, AZ, USA.
Richard A
RA
Manch
Hepatology Center for Liver and Hepatobiliary Disease, St. Joseph's Hospital and Medical Center, Phoenix, AZ, USA.
Ann
A
Moore
Hepatology Center for Liver and Hepatobiliary Disease, St. Joseph's Hospital and Medical Center, Phoenix, AZ, USA.
Anita
A
Kohli
Hepatology Center for Liver and Hepatobiliary Disease, St. Joseph's Hospital and Medical Center, Phoenix, AZ, USA.
Robert
R
Gish
Division of Abdominal Transplantation, Baylor College of Medicine, Houston, TX, 77030, USA.
Norman L
NL
Sussman
Division of Abdominal Transplantation, Baylor College of Medicine, Houston, TX, 77030, USA.
Saira
S
Khaderi
Division of Allergy and Infectious Diseases, University of Washington, Seattle, WA, USA.
John
J
Scott
Infectious Diseases, Cherokee Nation Health Services, Oklahoma, USA.
Jorge
J
Mera
Utah Department of Internal Medicine, Division of Gastroenterology, Hepatology and Nutrition, University of Utah, Salt Lake City, USA.
Terry
T
Box
Project ECHO, School of Medicine, University of New Mexico Health Sciences Center, Albuquerque, USA.
Clifford
C
Qualls
Project ECHO, School of Medicine, University of New Mexico Health Sciences Center, Albuquerque, USA.
Miranda
M
Sedillo
Division of Gastroenterology and Hepatology, Department of Internal Medicine, University of New Mexico Health Sciences Center, Albuquerque, USA.
Sanjeev
S
Arora
D000368:Aged; D000998:Antiviral Agents / Q000008:administration & dosage*; D005260:Female; D016174:Hepacivirus / Q000187:drug effects* / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000821:virology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D012367:RNA, Viral / Q000235:genetics; D012189:Retrospective Studies; D012307:Risk Factors; D000069474:Sofosbuvir / Q000008:administration & dosage*; D000072230:Sustained Virologic Response; D016896:Treatment Outcome; D019562:Viral Load / Q000187:drug effects
D000998:Antiviral Agents; D012367:RNA, Viral; D000069474:Sofosbuvir
HCV; Hepatitis C; Project ECHO; Response-guided therapy; Sofosbuvir