Dynamic characteristics of HIV-1 reservoirs

To examine kinetic issues related to the stability of the latent reservoir and the observation of low levels of viremia (< 50 copies/ml) in patients treated with highly active antiretroviral therapy.

Once HIV-1 RNA becomes undetectable it is difficult to deduce the events occurring in HIV-infected individuals. Analyses of viral blips and genetic changes in HIV-1 DNA have, however, provided insights into ongoing viral replication and the stability of the latent reservoir.

Under potent therapy, HIV-1 RNA decays in two phases and then becomes undetectable by clinical assay. Three possible scenarios are explored: the viral load stabilizes at a new steady state, or viral clearance remains more rapid than viral production and viral load declines either in a third exponential phase that might reflect the half-life of the latent reservoir, or in a decelerating manner reflecting heterogeneities in the cell populations making up the latent reservoir. A simple model shows that depending on the viral burst size it may be possible to sustain a low approximately steady level of viremia, say 10 copies/ml, for years without seriously depleting the latent reservoir.