Viral Dynamics in Hepatitis B Virus Infection

• Published in: Proceedings of the National Academy of Sciences - PNAS 1996-04, Vol.93 (9), p.4398-4402
• Main Authors: Nowak, Martin A., Bonhoeffer, Sebastian, Hill, Andrew M., Boehme, Richard, Thomas, Howard C., McDade, Hugh
• Format: Article
• Language: English
• Subjects: AIDS/HIV; Alanine Transaminase - blood; Antiviral Agents - therapeutic use; Antivirals; Cellular immunity; Dose-Response Relationship, Drug; Half lives; Hepatitis antigens; Hepatitis B - drug therapy; Hepatitis B - virology; Hepatitis B e Antigens - blood; Hepatitis B virus; Hepatitis B virus - drug effects; Hepatitis B virus - physiology; Hepatocytes; HIV; HIV Infections - physiopathology; HIV Infections - virology; Humans; Infections; Kinetics; Lamivudine; Liver cells; Models, Biological; Regression Analysis; Reverse Transcriptase Inhibitors - therapeutic use; Time Factors; Viremia - drug therapy; Viremia - virology; Virus Replication - drug effects; Virus Replication - physiology; Viruses; Zalcitabine - analogs & derivatives; Zalcitabine - therapeutic use
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.93.9.4398

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 ≈ 1.0 day, which implies a 50% daily turnover of the free virus population. Total virus release into the periphery is ≈ 1011 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.