Restriction of Hepatitis C Virus Heterogeneity during Prolonged Interferon-a 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 HVC strains may occur during prolonged IFN-alpha treatment, concomitant with general suppression of the viral replication.