Monday, November 25, 2013

HCV Viral Load at Baseline Sets Need for Protease Inhibitors

HCV Viral Load at Baseline Sets Need for Protease Inhibitors

Published: Nov 25, 2013

By Cole Petrochko, Staff Writer, MedPage Today
Reviewed by F. Perry Wilson, MD, MSCE; Instructor of Medicine, Perelman School of Medicine at the University of Pennsylvania

Hepatitis C genotype I patients with low viral load and sustained virologic response may be able to cut protease inhibitors from therapy, researchers found.

Among a cohort of treatment-naive, noncirrhosis hepatitis C patients with low viral load at baseline, those who achieved an undetectable viral load after 4 weeks of peginterferon alfa-2b and ribavirin had no significant differences in sustained viral load when continued on double-drug therapy versus triple-drug therapy that included a protease inhibitor, according to Brian Pearlman, MD, of the Center for Hepatitis C at the Atlanta Medical Center in Georgia, and Carole Ehleben, EdD, also of Atlanta Medical Center.

These similarities remained regardless of viral subtype -- genotypes 1a or 1b -- or interleukin 28b genotypes, as well as ethnicity (black versus white), they wrote online in the journal Hepatology.

Recent clinical trial data demonstrated the "near perfect cure rates" of a four-drug hepatitis C virus (HCV) treatment as part of the SAPPHIRE-1 study. Other all-oral treatments containing two- and three-drug combinations have also shown to be well tolerated and safe, with cure rates of 89% or greater.

The authors noted that the current standard of therapy for treatment-naive HCV genotype I patients is a triple therapy of peginterferon, ribavirin, and a protease inhibitor. They studied whether the inclusion of a protease inhibitor in such patients who achieve rapid virologic response after 4 weeks of peginterferon and ribavirin therapy was necessary. The study population included 233 patients with low HCV viral load at baseline who did not have cirrhosis.

Baseline characteristics the researchers recorded included age, sex, body mass index, fasting glucose, 25-hydroxyvitamin D levels, ethnicity, histological results of pretreatment liver biopsy, and quantitative HCV viral load. Patients were stratified by HCV genotype and interleukin-28b genotype.

Roughly half of the sample (48%) achieved rapid virologic response to the 4-week regimen, and these participants were randomized to either two- or three-drug therapy, with the three-drug group receiving 24 weeks of treatment and the two-drug group receiving 20 weeks of treatment.

At baseline and at monthly follow-up, researchers recorded participant's physical characteristics, weight, Beck's Depression Inventory, blood count and differential, hepatic profile, thyroid stimulating hormone, electrolytes, serum creatinine, serum uric acid, and serum beta-human chorionic gonadotropin testing.

In addition to virologic response, adverse event profiles were not significantly different between two- and three-drug groups, nor were dose reductions and discontinuation.

"Baseline patient ethnicity, viral subtype, and interleukin-28b genotype did not seem to impact sustained virologic response rates ultimately, regardless of therapy used," they concluded, adding that these findings amplify "the point that on-treatment predictors of therapy success trump pretreatment expectations."

They also noted that protease inhibitors "are costly, and are not yet available in many countries that lack the monetary resources to cover them," and that these findings may present a significant cost savings in at least those HCV patients with a low viral load.

They cautioned that their research was limited to patients who had a low viral load at baseline, and these results may not generalize to patients with a high viral load at baseline. In addition, the study was performed in a single center and had no formal statistical hypothesis testing.

Pearlman declared support from Merck

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