Restriction of hepatitis C virus heterogeneity during prolonged interferon-alpha therapy in relation to changes in virus load

To determine how interferon-alpha (IFN-alpha) treatment changes the heterogeneity of the hepatitis C virus (HCV) population, the hypervariable region 1 (HVR1) was directly sequenced, and the virus load was quantified in 15 patients who had received IFN-alpha for 15 months, Before treatment, 13 patients exhibited heterogeneous HVR1 sequences, In 7 subjects who did not respond or did not sustain a response to treatment, significantly decreased heterogeneity of the HVR1 was found at the end of treatment (P = .01), In 6 of these patients, the virus load decreased in parallel with the changes in HVR1 heterogeneity, At follow-up, both the virus load and the heterogeneity increased in 4 patients, and the virus load, but not the heterogeneity, increased in 2, In the seventh patient, the virus load steadily increased during treatment and follow-up, These results suggest that a selection of HCV strains may occur during prolonged IFN-alpha treatment, concomitant with general suppression of the viral replication.