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 he terogeneity of the hepatitis C virus (HCV) population, the hypervariab le region 1 (HVR1) was directly sequenced, and the virus load was quan tified in 15 patients who had received IFN-alpha for 15 months, Before treatment, 13 patients exhibited heterogeneous HVR1 sequences, In 7 s ubjects who did not respond or did not sustain a response to treatment , significantly decreased heterogeneity of the HVR1 was found at the e nd of treatment (P = .01), In 6 of these patients, the virus load decr eased in parallel with the changes in HVR1 heterogeneity, At follow-up , both the virus load and the heterogeneity increased in 4 patients, a nd the virus load, but not the heterogeneity, increased in 2, In the s eventh 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 s uppression of the viral replication.