The lymph node has been implicated as a potential site of ongoing HIV replication in treated persons living with HIV. Various studies have shown reduced concentrations of certain antiretrovirals (ARVs) within the lymph node parenchyma (or lobule), and some of these studies have shown elevated levels of HIV RNA associated with the regions of reduced ARV. In order to further investigate the hypothesis that lymph nodes may act as a sanctuary site in treated HIV infection, we have developed a predictive computational model of ARV and HIV dynamics within the lymph node. This model is computed on the reconstructed 3D geometry of real lymph nodes. Using this model, we are able to replicate the spatial patterns of ARV distribution seen in MALDI imaging of rhesus macaque lymph nodes. We have shown that, for several ARVs, transport within the lymph node is almost exclusively intracellular, which limits the penetration into the lymph node far from the blood supply. We have also shown that the lymph nodes are sufficiently isolated from the blood and fluid lymph to allow for sustained HIV replication even when HIV is suppressed systemically, assuming very low ARV efficacy within the lymph node. Under these circumstances, very few infected cells or virions exit the lymph nodes, so the ongoing replication is predicted to be undetectable from blood measurements, and it will take decades before genetic drift becomes detectable. Further work is necessary to determine whether the conditions necessary for this behavior in the computational model are seen in treated persons living with HIV.
Dr. Ryan Zurakowski joined the University of Delaware in 2006 following a PhD in Electrical and Computer Engineering from UCSB and a postdoc in Ecology and Evolutionary Biology at UC Irvine. The Zurakowski lab develops computational models of disease processes, with a special emphasis on within-host dynamics of HIV infection in treated patients. Dr. Zurakowski is currently serving as the interim chair of the Biomedical Engineering department.