VIRAL DYNAMICS IN-VIVO - LIMITATIONS ON ESTIMATES OF INTRACELLULAR DELAY AND VIRUS DECAY

Anti-viral drug treatment of human immunodeficiency virus type 1 (HIV- 1) and hepatitis B virus (HBV) infections causes rapid reduction in pl asma virus load. Viral decline occurs in several phases and provides i nformation on important kinetic constants of virus replication in vivo and pharmacodynamical properties. We develop a mathematical model tha t takes into account the intracellular phase of the viral life-cycle, defined as the time between infection of a cell and production of new virus particles. We derive analytic solutions for the dynamics followi ng treatment with reverse transcriptase inhibitors, protease inhibitor s, or a combination of both. For HIV-I, our results show that the phas e of rapid decay in plasma virus (days 2-7) allows precise estimates f or the turnover rate of productively infected cells. The initial quasi -stationary phase (days 0-1) and the transition phase (days 1-2) are e xplained by the combined effects of pharmacological and intracellular delays, the clearance of free virus particles, and the decay of infect ed cells, Reliable estimates of the first three quantities are not pos sible from data on virus load only; such estimates require additional measurements. In contrast with HIV-1, for HBV our model predicts that frequent early sampling of plasma virus will lead to reliable estimate s of the free virus half-life and the pharmacological properties of th e administered drug. On the other hand, for HBV the half-life of infec ted cells cannot be estimated from plasma virus decay.