Drug resistance in acute viral infections: Rhinovirus as a case study

The emergence and spread of drug resistant virus variants reflects both within-host and between-host processes. We develop an epidemiological model that can be used to address the spread of resistance at the population level, and a virus dynamics model that can be used to study the dynamics of virus over the time course of an individual’s infection. The dynamics depend in an important way on the competition between drug sensitive and drug resistant virus strains. A key observation is that the strength of competition between strains is strongly modulated by the degree of cross-immunity that infection with one strain confers against infection with the other. At the within-host level, we see that an efficient immune response can reduce the likelihood of the emergence of resistant virus. Consequently, resistance poses more of a problem for chronic infections in which there is significant immune impairment than for acute infections. These findings are discussed in the setting of rhinovirus infections, which are an important cause of infection in humans and for which novel antiviral drugs are being developed.