Influence of Peak Viral Load on the Extent of CD4+ T-Cell Depletion in Simian HIV Infection

Simian HIV (SHIV) infection of macaques with CXCR4 tropic viruses results in early and profound CD4 T-cell depletion in the first few weeks of infection. Analyzing data from a large study of vaccination and SHIV-89.6P challenge, we observe a strong correlation between peak viral load and the extent of CD4 T-cell depletion in acute infection, consistent with a simple kinetic model of viral infection of CD4 T cells. We have modeled the dynamics of the interaction of virus and CD4 T cells over time to investigate the rate of CD4 T-cell infection and death. This analysis indicates that up to 80% of CD4 T cells are infected at peak viremia and that the proportion of CD4 T cells destroyed is correlated with the peak viral load. The simple relation between viral load and CD4 T-cell depletion allows prediction of the level of viral control required to prevent CD4 T-cell depletion in acute SHIV infection. Whether such a simple relation also holds for HIV or simian immunodeficiency virus infections remains to be determined, particularly in the gut and other anatomic sites in which most early T-cell depletion occurs.