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Session 27 Oral Abstract Session Hepatitis B and C Co-Infection Session Time: Wednesday, 10 am - 11:15 am Room 6E

10:00   121. Early HCV Viral Dynamics in HIV/HCV-Infected Patients on HCV Treatment F. J. Torriani*1, R. M. Ribeiro2, T. L. Gilbert1, U. M. Schrenk3, M. Clauson1, D. M. Pacheco1, and A. S. Perelson2 1Univ. of California, San Diego; 2Los Alamos Natl. Lab., NM; and 3Hoffmann La-Roche Pharmaceuticals, Basel, Switzerland Background: On daily interferon (5-15 mIU), plasma HCV RNA follows a biphasic viral decay curve, with a HCV viral half-life of 2.7 hours. If HCV clearance is slower in HIV/HCV patients, longer treatment may be required to ensure sustained response rates similar to those seen in HCV monoinfection. We characterized the early HCV viral dynamics in 10 subjects naïve to HCV therapy and enrolling in a large randomized, partially blinded trial of pegylated interferon-2a (PEG) + ribavirin/placebo (+/-RIB) vs interferon-2a (IFN) + RIB. The infected cell death rate was also compared to the decline in ALT levels over the initial 4 weeks of therapy. Methods: Plasma HCV RNA IU/mL and HIV RNA copies/mL were measured before starting HCV treatment (BSL), 6, 8, 12, 24, 32, 48 hours and 3, 4, 7, 9, 11, 14, 21, and 28 (W4) days (D) after BSL. CD4 counts were measured at BSL, ALT levels at BSL, D7, D14, W4. Non-linear least squares were used to fit a model of HCV therapy, which allowed calculating the parameters of viral decay and early antiviral efficacy. Results are in mean±SE. Results: 8 of 10 subjects completed 24 weeks of study. Subjects were middle-aged men, infected with HCV genotype 1, 4 randomized to PEG+/-RIB and 4 to IFN+RIB. HAI and fibrosis scores were 6.4±0.7 and 2.3±0.5, respectively, and 1 subject had compensated cirrhosis. At BSL, HCV RNA, HIV RNA, absolute and % CD4 counts, and ALT were 5.4±0.4 log10 IU/mL, 2.2±0.4 log10 copies/mL, 625±93 cells/mm3, 30±4 % and 120±20 IU/mL, respectively. HCV RNA became undetectable in < 5 days in 2 subjects and in 28 days in a third. HCV RNA levels decreased slightly and transiently in 3 subjects and were overall unchanged in 1. In the remaining patient, HCV RNA was not detected at BSL, but only 6 and 12 hours post-treatment. In the 5 subjects with HCV RNA decline, the HCV virion half-life was of 7.0±1.0 hours and the early antiviral efficacy was 78±9%. ALT decline paralleled plasma HCV RNA decline in the 3 subjects exhibiting a virologic response at 24 weeks. Conclusions: The estimated HCV virion half-life was longer in this small cohort of HIV/HCV infected patients on HCV treatment than that observed in patients infected with HCV alone receiving daily interferon, suggesting that HIV co-infection may be contributing to a slower clearance rate of HCV.

©2002 9th Conference on Retroviruses and Opportunistic Infections