3rd International AIDS Society Conference on HIV Pathogenesis and Treatment Rio de Janeiro - July 24 - 27, 2005

DIFFERENTIAL ANTI-VIRAL EFFECT OF PEG-IFN ON HIV AND HCV IN TREATMENT OF HIV/HCV CO-INFECTED PATIENTS

IAS Conf HIV Pathog Treat 2005 Jul 24-27;3rd: Abstract No. WePe3.3C17

Neumann A.¹, Wu L.², McLaughlin M.², Koratich C.², Rehm C.², Masur H.³, Kottilil S.², Polis M.^2
1Bar-Ilan University, Ramat-Gan, Israel, ²LIR, NIAID, NIH, DHHS, Bethesda, MD, United States of America, ³CCMD, CC, NIH, DHHS, Bethesda, MD, United States of America

INTRODUCTION: The major anti-viral effect of Interferon-alpha on HCV is blocking of virion production from infected cells (Neumann, AU et al. Science. 1998 Oct 2;282(5386):103-7). However, the mechanism of action of IFN against HIV is unknown and previous studies of HIV kinetics during IFN treatment had only sparse data. Here we study HIV kinetics during Pegylated-interferon alfa-2b (PEG-INTRON®) treatment of HIV/HCV co-infected patients.

METHODS: HIV/HCV co-infected genotype 1 patients (N=23; mean 612 CD4 cells/mm³) were treated with Peg-IFN alfa-2b 1.5µg/kg qw and ribavirin 1200mg qd for 48 wks. HIV-RNA was quantified by bDNA assay in the 9 patients with detectable HIV-RNA (mean 3.5 log cp/ml, range 2.1 – 5.1).

RESULTS: HIV and HCV present clearly different patterns of viral kinetics. HCV shows rapid first phase decline followed by slower decline and rebound at the end of the week, concomitant with decline in Peg-IFN levels. HIV shows slow continuous decline during the whole week. Fitting of HCV kinetics is in agreement with assumption that IFN blocks HCV production. However, when attempting to fit HIV kinetics with a model that assumes Peg-IFN blocks HIV production one must assume a half-life of HIV-free virions of 1 – 2 days or a half-life of HIV-infected cells of 0.3 – 0.5 days, both in clear contradiction with previous studies. Fitting the data with the model is possible when assuming that Peg-IFN major effect against HIV is blocking de novo infection. The mean decline half-life of infected cells is then 1.3 days and the estimate of free virions half-life is in agreement with previous data (<6 hours). The effectiveness of Peg-IFN in blocking infection is of similar magnitude to ARVs assessed from historical comparison. Interestingly, fitting indicates that HIV rebound observed is a pharmacodynamic effect and not resistance.

CONCLUSION: These novel results indicate that IFN suppresses HIV by blocking de novo infection effectively, rather than blocking production as seen with HCV. In vitro studies are currently conducted to corroborate these results experimentally.

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050724
Clinical | WePe3.3C17 | Avidan Neumann
Drug Interactions

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