Intermittent viremia in HIV-1 infected patients receiving antiretroviral therapy: a dynamical point of view.

Duncan Callaway and Alan S. Perelson

Despite the demonstrated potency of antiretroviral regimens, HIV-1 infected patients, in whom therapy reduces viral load to below 50 HIV RNA copies/mL, exhibit periods of intermittent viremia. This phenomenon could be accounted for by a patient's poor adherence to the drug protocol, or occasional expansion of the target cell pool due to secondary infection. In this study, we offer an alternative explanation based upon the consequences of in vivo viral population dynamics. We develop a mathematical model that mimics the effect of drug therapy in HIV infected patients and exhibits a robust, low steady state viral load (5 orders of magnitude lower than viral load in the absence of drug therapy). This steady state is achieved by including a drug resistant target cell compartment, in addition to the standard primary compartment used in earlier models. In this model, simulation of therapy results in damped oscillatory viral dynamics with a period of approximately 3-6 months. Though for the majority of the period of oscillation the viral load is below 50 copies/mL, the peaks of the oscillations can be as large as 200 copies/mL, which is similar in value to viral loads observed during intermittent episodes of plasma viremia in clinical studies. Based upon numerical studies of the model, we predict that as the time since the initiation of therapy increases, the likelihood of observing "blips" in viral load decreases. Furthermore, the model suggests that patients in whom the initial decay in viral load is slow should be less likely to exhibit blipping behavior. The results of this model stress the importance of even a small population of drug resistant target cells, and the role they play in preventing the eradication of HIV-1 infection from individual patients.

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