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184

EARLY PHASE HEPATITIS C VIRUS (HCV) LOAD RESPONSE TO INTERFERON/RIBAVIRIN THERAPY

FH Anderson, N Rock, L Walston, A Mak, K Gunadasa, P Cook, WD Hill, M Krajden

Vancouver General Hospital, British Columbia Centre for Disease Control, University of British Columbia, Vancouver, British Columbia

OBJECTIVE: The use of HCV load to monitor therapeutic response remains problematic. Current data are based on the National Genetics Institute (NGI) assay, which is not equivalent to commercial quantitative detection assays. Given the widespread use of commercial HCV detection assays it is important to define how they can be used to monitor new antiviral therapies. Early predictions as to persons likely to respond to therapy may alter the time course of therapy required.

METHODS: Viral loads in a community-based cohort of 139 naïve patients undergoing Interferon/Ribavirin therapy were followed. The group comprised 64% genotype 1 (mean age 45 and 36% non-genotype 1 (mean age 44). Genotypes were determined by the INNO-LIPA HCV II assay (Innogenetics). Viral load determinations were performed by the COBAS AMP{LICOR HCV monitor v.2.0 (Roche) at weeks 0,1,2,3,4,8, 12 and 24. Additional testing will include weeks 28 and 74 for non-genotype 1 and weeks 48,74, and 100 for genotype 1.

RESULTS: The pretreatment viral load in LOG(10)IU/ml for genotype 1 was 5.70 and 5.68 for non-genotype 1. Early therapeutic response was defined as HCV RNA below the limit of detection of the AMPLICOR HCV Monitor assay. As of weeks 4 and 8, 23% and 43% respectively of genotype 1 patients fell below the detection limit. In contrast, 75% of the non-genotype 1 patients went below the detection limit at week 4 and 89% by week 8. Since the lower limit of detection of the AMPLICOR monitor assay is 600 IU/ml, the end of treatment response (EOT) and sustained response (SR) were evaluated by the more sensitive COIBAS HCV qualitative PCR for which the lower limit of detection is 50 IU/ml.

CONCLUSIONS: Preliminary results demonstrate that the majority of non-responders to Interferon/Ribavirin can be identified by week 8, however, EOT and SR are required to assess the overall response rate. Our results also confirm that significant differences exist between the response profiles of genotype 1 and non-genotype 1 infected patients.