title: Increased inflammation in sanctuary sites may explain viral blips in HIV infection.
abstract: Combined antiretroviral therapy (cART) suppress HIV-1 viral replication, such that viral load in plasma remains below the limit of detection in standard assays. However, intermittent episodes of transient viremia (blips) occur in a set of HIV-patients. Given that follicular hyperplasia occurs during lymphoid inflammation as a normal response to infection, it is hypothesised that when the diameter of the lymph node follicle (LNF) increases and crosses a critical size, a viral blip occurs due to cryptic viremia. To study this hypothesis, a theoretical analysis of a mathematical model is performed to find the conditions for virus suppression in all compartments and different scenarios of LNF size changes are simulated. According to the analysis, blips with duration of around 30 days arise when the diameter rise rate is between 0.02 and 0.03 days(-1). Moreover, the final diameter of the site is directly related to the steady states of the virus load after the occurrence of a blip. When the value of R0 is around 2.1, to have a steady-state below the limit of detection after the viral blip, the maximum final diameters should be greater than 0.7 mm so that there is a relative loss of connection between compartments.
authors.affiliation: Theoretical Biology and Biophysics Group, Los Alamos National Laboratory, Los Alamos, New Mexico 87545, USA. fabian_c@lanl.gov.
authors.forename: E Fabian
authors.initials: EF
authors.lastname: Cardozo
authors.affiliation: Electrical Engineering Department, Pennsylvania State University, Malvern, Pennsylvania 19355, USA.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Piovoso
authors.affiliation: Electrical and Computer Engineering Department, University of Delaware, Newark, Delaware 19716, USA.
authors.forename: Ryan
authors.initials: R
authors.lastname: Zurakowski
mesh_terms: D015658:HIV Infections / Q000276:immunology*; D015497:HIV-1; D006801:Humans; D007249:Inflammation; D008962:Models, Theoretical; D019562:Viral Load; D014766:Viremia