Anti-viral drug treatment: Dynamics of resistance in free virus and infected cell populations

Anti-viral drug treatment of infections with the human immunodeficiency virus type 1 (HIV-1) usually leads to a rapid decline in the abundance of plasma virus. The effect of single drug therapy, however, is often only short-lived as the virus readily develops drug-resistant mutants. In this paper we provide analytic approximations for the rate of emergence of resistant virus. We study the decline of wildtype virus and the rise of resistant mutant virus in different compartments of the virus population such as free plasma virus, cells infected with actively replicating virus, long-lived infected cells and cells carrying defective provirus. The model results are compared with data on the rise of drug-resistant virus in three HIV-1 infected patients treated with neverapine (NVP). We find that the half-life of latently infected cells is between 10 and 20 days, whereas the half-life of cells with defective provirus is about 80 days. We also provide a crude estimate for the basic reproductive ratio of HIV-1 during NVP therapy. (C) 1997 Academic Press Limited.