In the Journals

Model Accurately Predicts Rapid Response in HCV at 4 Weeks

Multiple variables, including IL28B genotype with viral load, HCV genotype, Forns’ Index and HIV coinfection were used to construct a model that accurately predicted virological response at 4 weeks in patients with hepatitis C virus infection treated with pegylated interferon alfa-2a and ribavirin, according to study data.

The goal of the prospective research was to develop a prognostic tool to predict viral response of patients with HCV within the first 4 weeks of therapy with PEG-IFN a-2a and ribavirin, which included measuring rates of rapid virological response (RVR) and any HCV RNA decline of < 1 log₁₀ IU/mL (D1L). The study included 538 patients with HCV and 186 patients coinfected with HIV and HCV who were separated to form an estimation cohort to construct the model for measuring RVR and D1L and a validation cohort to validate the model. Each patient received 180 µ per week of PEG-IFN a-2a in combination with weight-based ribavirin for 48 weeks. Of the patients, 74.8% had HCV monoinfection and 25.2% had HIV/HCV coinfection.

Overall, 22.5% of patients achieved RVR (n=148) and 80.2% experienced D1L (n=509). Achieving RVR was more prevalent in the monoinfected patients compared with the coinfected patients (26.8% vs. 10%; P < .001), as well as more prevalent in the genotype 4 patients compared with the genotype 1 patients (29.8% vs. 20.7%; P < .05). Patients coinfected with HIV and HCV had a lower prevalence of D1L compared with patients with only HCV (70.2% vs. 83.7%; P < .001). D1L was prevalent in HCV genotype 1 patients compared with genotype 4 (81.7% vs. 73%; P < .05).

The area under the receiver operating curve’s (AUROC) diagnostic accuracy for D1L was 0.81 in the estimation cohort and 0.71 in the validation cohort, with an AUROC RVR prediction of 0.83 in the estimation cohort and 0.82 in the validation cohort.   

Multivariate analysis showed HIV coinfection (P = .027), Forns’ Index (P < .001), low viral load (P < .001), IL28B polymorphism-CC (P < .001) and genotype 1 (P = .01) to be independently associated with RVR. The same variables were also associated with D1L, according to the research.   

In a cost analysis, 48 weeks of standard treatment showed a 30.3% savings if the Optim tool was used, according to the research.

“The combination of genetic and viral genotype together with viral load, HIV coinfection and fibrosis stage defined a tool to predict RVR and D1L at week 4,” the researchers concluded. “The implementation of this tool in clinical practice could be a cost-saving strategy, compared to the universal triple therapy for hepatitis C. As such, it could contribute to a more efficient allocation of limited resources.” – by Melinda Stevens

Disclosure: Oyagüez reports being employed by Pharmaceoconomics & Outcomes Research Iberia. Please see the full study for a list of all other authors’ relevant financial disclosures.

Multiple variables, including IL28B genotype with viral load, HCV genotype, Forns’ Index and HIV coinfection were used to construct a model that accurately predicted virological response at 4 weeks in patients with hepatitis C virus infection treated with pegylated interferon alfa-2a and ribavirin, according to study data.

The goal of the prospective research was to develop a prognostic tool to predict viral response of patients with HCV within the first 4 weeks of therapy with PEG-IFN a-2a and ribavirin, which included measuring rates of rapid virological response (RVR) and any HCV RNA decline of < 1 log₁₀ IU/mL (D1L). The study included 538 patients with HCV and 186 patients coinfected with HIV and HCV who were separated to form an estimation cohort to construct the model for measuring RVR and D1L and a validation cohort to validate the model. Each patient received 180 µ per week of PEG-IFN a-2a in combination with weight-based ribavirin for 48 weeks. Of the patients, 74.8% had HCV monoinfection and 25.2% had HIV/HCV coinfection.

Overall, 22.5% of patients achieved RVR (n=148) and 80.2% experienced D1L (n=509). Achieving RVR was more prevalent in the monoinfected patients compared with the coinfected patients (26.8% vs. 10%; P < .001), as well as more prevalent in the genotype 4 patients compared with the genotype 1 patients (29.8% vs. 20.7%; P < .05). Patients coinfected with HIV and HCV had a lower prevalence of D1L compared with patients with only HCV (70.2% vs. 83.7%; P < .001). D1L was prevalent in HCV genotype 1 patients compared with genotype 4 (81.7% vs. 73%; P < .05).

The area under the receiver operating curve’s (AUROC) diagnostic accuracy for D1L was 0.81 in the estimation cohort and 0.71 in the validation cohort, with an AUROC RVR prediction of 0.83 in the estimation cohort and 0.82 in the validation cohort.   

Multivariate analysis showed HIV coinfection (P = .027), Forns’ Index (P < .001), low viral load (P < .001), IL28B polymorphism-CC (P < .001) and genotype 1 (P = .01) to be independently associated with RVR. The same variables were also associated with D1L, according to the research.   

In a cost analysis, 48 weeks of standard treatment showed a 30.3% savings if the Optim tool was used, according to the research.

“The combination of genetic and viral genotype together with viral load, HIV coinfection and fibrosis stage defined a tool to predict RVR and D1L at week 4,” the researchers concluded. “The implementation of this tool in clinical practice could be a cost-saving strategy, compared to the universal triple therapy for hepatitis C. As such, it could contribute to a more efficient allocation of limited resources.” – by Melinda Stevens

Disclosure: Oyagüez reports being employed by Pharmaceoconomics & Outcomes Research Iberia. Please see the full study for a list of all other authors’ relevant financial disclosures.