Genotype-Resistance-Testing (GRT) Can Optimize Treatments for Patients with HCV

A recent multi-center, real-life efficacy study found good evidence that genotype-resistance-testing (GRT) is successful in helping clinicians identify the most effective alternative treatment regimens for patients with Hepatitis C Virus genotype 1 who have experienced protease inhibitor (PI) resistance.

An interdisciplinary group of researchers at several Italian universities led by Valeria Cento, PhD, a researcher and Academic Fellow with the Department of Experimental Medicine and Surgery at the University of Rome in Italy, focused on interferon-free treatment of patients with Hepatitis C Virus (HCV) genotype 1 (GT-1) and advanced liver disease who have failed to respond to standard protease-inhibitor (PI) treatment regimens. The group discovered that using genotypic-resistance-testing (GRT) to pinpoint the best treatment options for patients with PI-experience allowed clinicians to optimize retreatment of those patients leading to increased likelihood of sustained virological response (SVR).

Dr. Cento and colleagues point out that one consistent obstacle to HCV treatment is the development of patient resistance to protease inhibitors. Currently there are several resistance associated substitutions (RAS) for PIs available, but there are increased risks of cross-resistance developing in patients who use RAS for treatment. Cento points out that currently the European Association for the Study of the Liver (EASL)-American Association for the Study of Liver Diseases (AASLD) recommend a combination of specific inhibitors as part of treatment in order to decrease cross-resistance risk, but their research shows that the inclusion of baseline GRT testing to determine precise retreatment options greatly decreases the risk of further resistance, and increases the likelihood of patients achieving SVR.

The study included 121 patients divided into three different treatment groups. Patients in group A were given GRT which guided the selection of RAS for those patients’ treatment regimens. Patients in group B were treated with regimens based on EASL-AASLD recommended guidelines for treatment. Group C was treated with regimens outside of EASL/AASLD guidelines without GRT-guidance.

The researchers discovered that although the overall SVR rate after treatment with RAS for all three groups was 91%, the “18 patients treated with ‘GRT-guided’ regimens reached SVR 100% despite,” as the study points out, “heterogeneity in treatment duration” of those 18 patients.

Patients in the other two groups (B and C) had statistically significant decreases in their SVR percentages. Those patients in the AASLD/EASL recommended group (B) saw only slightly lower success rates for SVR at 94.4% in comparison to the GRT-guided group (A), but those patients in the group outside the GRT-guided and AASLD/EASL recommended groups (C) saw a “strongly reduced” SVR percentage of 77.4%.

Cirrhotic patients in the two non-GRT-guided groups (B and C) had significantly decreased success with treatment overall. Additionally, the researchers found that PI-free regimens were more highly effective in those groups with patients who (in a “a posteriori baseline-GRT”) were revealed to have natural levels of nonstructural protein 5A resistance.

Cento points out that baseline-GRT for patients with HCV is commonly used in the United States, but has been slow to be adopted in Europe as a means of establishing treatment, or retreatment in the case of PI-resistance, regimens. The group hopes that their success with GRT-guided PI-free regimens will inspire more GRT-guided testing to establish effective, personalized treatment plans for patients with HCV and PI-resistance. Cento states that a GRT-guided approach to establishing treatment regimens would “limit as much as possible the chances of second-line failures and further development of multiresistant viruses, as well as high costs of third-line therapies.”

The article “Optimal Efficacy of Interferon-Free HCV Retreatment after Protease Inhibitors Failure inReal Life” was published by Clinical Microbiology and Infection online in April 2017 and is forthcoming in a 2017 print issue.

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