Modelling HIV-1 2-LTR dynamics following raltegravir intensification

Modelling HIV-1 2-LTR dynamics following raltegravir intensification

Online publication: 08/05/2013


 A model of reservoir activation and viral replication is introduced accounting for the production of 2-LTR HIV-1 DNA circles following antiviral intensification with the HIV integrase inhibitor raltegravir, considering contributions of de novo infection events and exogenous sources of infected cells, including quiescent infected cell activation. The model shows that a monotonic increase in measured 2-LTR concentration post intensification is consistent with limited de novo infection primarily maintained by sources of infected cells unaffected by raltegravir, such as quiescent cell activation, while a transient increase in measured 2-LTR concentration is consistent with significant levels of efficient (R0 > 1) de novo infection. The model is validated against patient data from the INTEGRAL study and is shown to have a statistically significant fit relative to the null hypothesis of random measurement variation about a mean. We obtain estimates and confidence intervals for the model parameters, including 2-LTR half-life. Seven of the 13 patients with detectable 2-LTR concentrations from the INTEGRAL study have measured 2-LTR dynamics consistent with significant levels of efficient replication of the virus prior to treatment intensification. Read online in the Journal of the Royal Society or download the paper (PDF | 1MB)

Authors: Rutao Luo1, E. Fabian Cardozo1, Michael J. Piovoso2, Hulin Wu3, Maria J. Buzon4,†, Javier Martinez-Picado4,5 and Ryan Zurakowski1 1Department of Electrical and Computer Engineering, University of Delaware, Newark, DE, USA 2Department of Electrical Engineering, Pennsylvania State University, Malvern, PA, USA 3Department of Biostatistics and Computational Biology, University of Rochester, New York, NY, USA 4irsiCaixa Foundation, Barcelona, Spain 5ICREA, Barcelona, Spain
  • Doi Code: doi: 10.1098/rsif.2013.0186

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