A compartment based model for the formation of 2-LTR circles after raltegravir intensification

Highly Active Antiretroviral Therapy (HAART) can suppress measured Human Immunodeficiency Virus (HIV) plasma viral load below the standard limits of detection in most HIV-positive patients. However it has been shown that the virus persists at undetectable levels and rebounds rapidly when the treatment is interrupted. It has been hypothesized that the virus may continue to replicate efficiently in anatomical compartments with low antiviral concentration, so called “cryptic viremia”. Recent results from an experiment measuring the dynamics of 2-LTR HIV DNA episomes following intensification with the integrase inhibitor raltegravir have provided strong support for the “cryptic viremia” hypothesis. In this paper we introduce a multi-compartment model of HIV viral dynamics including 2-LTR episome concentrations. These compartments represent an isolated anatomical location similar in structure to a lymph node, with diffusion from the plasma decreasing with distance from the plasma. We show that when the size of the compartment is sufficiently large to allow efficient replication in the most remote compartment, the dynamics of measured 2-LTR in the plasma compartment is consistent with the observed patterns in the raltegravir intensification experiment, providing support to the “cryptic viremia” hypothesis. The model presented could be adapted for use in estimating cryptic viremia dynamics from 2-LTR measurements.

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