On the role of resonance in drug failure under HIV treatment interruption

Background: The application of highly active antiretroviral therapy (HAART) against HIV can reduce and maintainviral load below detection limit in many patients. Continuous HAART, however, can have severe sideeffects. In this context, structured treatment interruptions (STI) were considered to be a promisingstrategy. However, using CD4 cell count to guide intermittent therapy starting and stopping points, theSMART study (strategies for management of antiretroviral therapy), revealed that STI were associatedwith increased risk of AIDS and other complications. Additionally, short-term periodic (e.g. oneweek on / one week off) interruption therapies have shown virus rebound exceeding a given "failurethreshold", without any evidence for the evolution of drug resistance. Currently, the only hypothesisexplaining the failure of STI is the "resonance hypothesis", which posits that treatment failure is due toa resonance effect between the drug treatment and the viral population. In the present study we used amathematical model to analyse the parameters affecting the output of drug treatment interruption andthe premises of the resonance hypothesis. Methods: We used a population dynamic model of HIV infection. Simulations and analytical approximations ofdeterministic and stochastic versions of the model were studied.Results and conclusionThe present study examines the roles of the most important parameters affecting the viral rebound,responsible for drug failure. We related these findin...
Source: Theoretical Biology and Medical Modelling - Category: Biomedical Science Authors: Source Type: research