Stochastic HIV model coupled with pharmacokinetics and drug adherence may explain intermittent viral blips

Abstract

We develop a stochastic HIV model by integrating drug adherence into a pharmacokinetic model and by coupling a pharmacodynamic model with a viral dynamic model. Numerical simulations show that the proposed model can generate viral blips, which have been observed in HIV patients receiving suppressive antiretroviral therapy. We calculate the probability density function of infected CD4+ T cells by developing the generalized density evolution equation. We fit the model to the clinical data of four HIV patients exhibiting viral blips. The results demonstrate that poor drug adherence can be a reason explaining the occurrence of viral blips in treated HIV patients. We also find that viral dynamics are sensitive to drug-adherence parameters, which have a significant impact on the frequency and amplitude of viral blips. The modeling and methods can be applied to the study of long-term therapy of other chronic diseases in which drug adherence might also be an issue.