Sequential measurements of latently infected cells in patients on HAART have yielded half-lives ranging from 6 to 44 months. A recent study has suggested that the replication-competent latent reservoir declines more rapidly in patients whose plasma viral loads are consistently undetectable than in patients who show occasional viral blips. Other studies have shown that IL-2 treatment can reduce the number of latently infected cells in patients on HAART.

To gain insight into these observations and to evaluate prospects for viral eradication following HAART, the investigators have constructed and analyzed a mathematical model for the dynamics of the latently infected cell compartment. The model allows one to explore the effects that treatment interruptions, IL-2 administration, and changes in drug efficacy have on the replication-competent latent reservoir.

Transient viremias in patients on HAART are likely to reflect new rounds of infection, rather than wholesale activation of latently infected cells. The model predicts a nonlinear relationship between the increase in the latently infected pool and the length of therapy interruptions. To account for the slower decay rate in patients with occasional viral blips, the model requires an increase in either the infection rate constant or the probability of latency as viral loads decline. The model predicts that the decay rate of the latently infected cell compartment will decline over time if viral replication is not completely suppressed (even after productively infected cells have disappeared). This occurs because a transient viremia of a given size has a greater proportional effect on the latent reservoir when the reservoir is small. In patients with low densities of latently infected cells, the reduction in the density of latently infected cells following IL-2 treatment may be transient if viral replication is not completely suppressed.

Even with optimistic estimates for the intrinsic decay rate of latently infected cells, the transient increases in viral load observed in most patients on HAART will make it increasingly difficult to eliminate the remaining latently infected cells as the density of these cells declines (abstract 135)