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

Anti!viral drug treatment of infections with the human immunode_ciency virus type 0 "HIV!0 # usually leads to a rapid decline in the abundance of plasma virus [ The e}ect 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 di}erent 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!0 infected patients treated with neverapine "NVP# [ We _nd that the half!life of latently infected cells is between 09 and 19 days \ whereas the half!life of cells with defective provirus is about 79 days[ We also provide a crude estimate for the basic reproductive ratio of HIV!0 during NVP therapy[ 7 0886 Academic Press Limited