Data from: HIV dynamics linked to memory CD4+ T cell homeostasis

The dynamics of latent HIV is linked to infection and clearance of resting
memory CD4+ T cells. Infection also resides within activated, non-dividing
memory cells and can be impacted by antigen-driven and homeostatic
proliferation despite suppressive antiretroviral therapy (ART). We
investigated whether plasma viral level (pVL) and HIV DNA dynamics could
be explained by HIV’s impact on memory CD4+ T cell homeostasis. Median
total, 2-LTR and integrated HIV DNA levels per μL of peripheral blood, for
8 primary (PHI) and 8 chronic HIV infected (CHI) individuals enrolled on a
raltegravir (RAL) based regimen, exhibited greatest changes over the 1st
year of ART. Dynamics slowed over the following 2 years so that total HIV
DNA levels were equivalent to reported values for individuals after 10
years of ART. The mathematical model reproduced the multiphasic dynamics
of pVL, and levels of total, 2-LTR and integrated HIV DNA in both PHI and
CHI over 3 years of ART. Under these simulations, residual viremia
originated from reactivated latently infected cells where most of these
cells arose from clonal expansion within the resting phenotype. Since
virion production from clonally expanded cells will not be affected by
antiretroviral drugs, simulations of ART intensification had little impact
on pVL. HIV DNA decay over the first year of ART followed the loss of
activated memory cells (120 day half-life) while the 5.9 year half-life of
total HIV DNA after this point mirrored the slower decay of resting memory
cells. Simulations had difficulty reproducing the fast early HIV DNA
dynamics, including 2-LTR levels peaking at week 12, and the later slow
loss of total and 2-LTR HIV DNA, suggesting some ongoing infection. In
summary, our modelling indicates that much of the dynamical behavior of
HIV can be explained by its impact on memory CD4+ T cell homeostasis.