VIRAL DYNAMICS IN HEPATITIS-B VIRUS-INFECTION

Treatment of chronic hepatitis B virus (HBV) infections with the rever se transcriptase inhibitor lamivudine leads to a rapid decline in plas ma viremia and provides estimates for crucial kinetic constants of HBV replication. We find that in persistently infected patients, HBV part icles are cleared from the plasma with a half-life of approximate to 1 .0 day, which implies a 50% daily turnover of the free virus populatio n. Total viral release into the periphery is approximate to 10(11) vir us particles per day. Although we have no direct measurement of the in fected cell mass, we can estimate the turnover rate of these cells in two ways: (i) by comparing the rate of viral production before and aft er therapy or (ii) from the decline of hepatitis B antigen during trea tment. These two independent methods give equivalent results: we find a wide distribution of half-lives for virus-producing cells, ranging f rom 10 to 100 days in different patients, which may reflect difference s in rates of lysis of infected cells by immune responses. Our analysi s provides a quantitative understanding of HBV replication dynamics in vivo and has implications for the optimal timing of drug treatment an d immunotherapy in chronic HBV infection. This study also represents a comparison for recent findings on the dynamics of human immunodeficie ncy virus (HIV) infection. The total daily production of plasma virus is, on average, higher in chronic HBV carriers than in HIV-infected pa tients, but the half-life of virus-producing cells is much shorter in HIV. Most strikingly, there is no indication of drug resistance in HBV -infested patients treated for up to 24 weeks.