Background:  Simian/human immunodeficiency virus (SHIV) infection results in rapid depletion of CD4⁺ T lymphocytes within the first 3 weeks of infection. Interventions such as vaccination and ART that reduce viral load in acute infection reduce the extent of CD4⁺ T cell loss during this period. Understanding the kinetics of CD4⁺ T-cell depletion and how the level and timing of viral load control affect this are important for the rational design of vaccines and early antiretroviral intervention.

Methods:  Using data from a study of vaccination and SHIV_89.6P challenge, we analyzed the relationship between peak viral load and CD4⁺ T-cell depletion in acute infection in 35 macaques. Simple differential equation models were used to understand the rate of infection and death of CD4⁺ T cells as a function of viral load.

Results:  Our analysis revealed a strong correlation between peak viral load and subsequent CD4⁺ T-cell depletion among the 35 macaques (r = 0.85, p <0.001, Spearman). Mathematical modelling of this relationship suggests a simple and predictable interaction between virus and CD4⁺ T cells, and allows us to estimate the ‘infectivity’ of virus. As this analysis was cross sectional, we also modelled the kinetics of CD4⁺ T-cell infection and death over time within individual animals. Again, this was consistent with our model of CD4⁺ T-cell infection and death and allows us to calculate the infectivity of virus in individual animals. From the model we derived a crucial relationship between the peak viral load and the number of CD4⁺ T cells infected and subsequently killed. In unvaccinated animals, peak viral loads of ~10⁸ copies/mL are associated with infection and loss of more than 90% of circulating CD4⁺ T cells. By contrast, a 10-fold reduction in peak viral load in some vaccinated animals reduces the CD4⁺ T cell loss to ~70%. Reduction of peak viral load by 100-fold leads to a loss of only ~12% of CD4⁺ T cells.

Conclusions:  This analysis allows us to predict the level of viral load control required to prevent significant CD4⁺ T cell depletion in acute SHIV infection. Thus, it allows us to understand how different interventions such as vaccination, passive antibody therapy, or early ART can program the long-term outcome of infection. Further studies are required to establish whether the simple relationship we found for SHIV infection exists between viral load and CD4⁺ T-cell depletion in HIV.