HIV-1 Dynamics In Vivo: Virion Clearance Rate, Infected Cell Lifespan, and Viral Generation Time

Using a new mathematical model to analyze a detailed set of viral load data collected from five infected patients after the administration of a potent inhibitor of HIV-1 protease, it was estimated that productively infected cells have, on average, a lifespan of $2.2$ days ($t_{1/2}=1.6$ days) and that plasma virions have a mean lifespan of $0.3$ days ($t_{1/2}=0.24$ days). The average total HIV-1 production was $10.3\times 10^9$ virions per day, which is substantially higher than previous minimum estimates. Our results also suggest that the minimum duration of the HIV-1 life cycle in vivo is $1.2$ days on average, and that the average HIV-1 generation time, defined as the time from release of a virion until it infects another cell and causes the release of a new generation of viral particles, is $2.6$ days. These findings on viral dynamics provide not only a kinetic picture of HIV-1 pathogenesis, but also the theoretical principles to guide treatment strategies.