Viral dynamics in hepatitis B virus infection.

Important note: Information in this article was accurate in 1996. The state of the art may have changed since the publication date.

Viral dynamics in hepatitis B virus infection.

Proc Natl Acad Sci U S A. 1996 Apr 30;93(9):4398-402. Unique Identifier : AIDSLINE MED/96210655
Nowak MA; Bonhoeffer S; Hill AM; Boehme R; Thomas HC; McDade H; Department of Zoology, University of Oxford, United Kingdom;

Abstract: Treatment of chronic hepatitis B virus (HBV) infections with the reverse transcriptase inhibitor lamivudine leads to a rapid decline in plasma viremia and provides estimates for crucial kinetic constants of HBV replication. We find that in persistently infected patients, HBV particles are cleared from the plasma with a half-life of approximately 1.0 day, which implies a 50% daily turnover of the free virus population. Total viral release into the periphery is approximately 10(11) virus particles per day. Although we have no direct measurement of the infected cell mass, we can estimate the turnover rate of these cells in two ways: (i) by comparing the rate of viral production before and after therapy or (ii) from the decline of hepatitis B antigen during treatment. These two independent methods give equivalent results: we find a wide distribution of half-lives for virus-producing cells, ranging from 10 to 100 days in different patients, which may reflect differences in rates of lysis of infected cells by immune responses. Our analysis provides a quantitative understanding of HBV replication dynamics in vivo and has implications for the optimal timing of drug treatment and immunotherapy in chronic HBV infection. This study also represents a comparison for recent findings on the dynamics of human immunodeficiency virus (HIV) infection. The total daily production of plasma virus is, on average, higher in chronic HBV carriers than in HIV-infected patients, but the half-life of virus-producing cells is much shorter in HIV. Most strikingly, there is no indication of drug resistance in HBV-infected patients treated for up to 24 weeks.

Keywords: Alanine Aminotransferase/BLOOD Antiviral Agents/THERAPEUTIC USE Dose-Response Relationship, Drug Hepatitis B/*DRUG THERAPY/*VIROLOGY Hepatitis B e Antigens/BLOOD Hepatitis B Virus/DRUG EFFECTS/*PHYSIOLOGY Human HIV Infections/PHYSIOPATHOLOGY/VIROLOGY Kinetics Models, Biological Regression Analysis Reverse Transcriptase Inhibitors/*THERAPEUTIC USE Support, Non-U.S. Gov't Time Factors Viremia/DRUG THERAPY/VIROLOGY Virus Replication/DRUG EFFECTS/*PHYSIOLOGY Zalcitabine/*ANALOGS & DERIVATIVES/THERAPEUTIC USE JOURNAL ARTICLE
960930
M9690886

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