Comparison of linear, nonlinear and semiparametric mixed-effects models for estimating HIV dynamic parameters
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The potency of antiretroviral agents in AIDS clinical trials can be assessed on the basis of an early viral response such as viral decay rate or change in viral load (number of copies of HIV RNA) of the plasma. Linear, parametric nonlinear, and semiparametric nonlinear mixed-effects models have been proposed to estimate viral decay rates in viral dynamic models. However, before applying these models to clinical data, a critical question that remains to be addressed is whether these models produce coherent estimates of viral decay rates, and if not, which model is appropriate and should be used in practice. In this paper, we applied these models to data from an AIDS clinical trial of potent antiviral treatments and found significant incongruity in the estimated rates of reduction in viral load. Simulation studies indicated that reliable estimates of viral decay rate were obtained by using the parametric and semiparametric nonlinear mixed-effects models. Our analysis also indicated that the decay rates estimated by using linear mixed-effects models should be interpreted differently from those estimated by using nonlinear mixed-effects models. The semiparametric nonlinear mixed-effects model is preferred to other models because arbitrary data truncation is not needed. Based on real data analysis and simulation studies, we provide guidelines for estimating viral decay rates from clinical data. 2004 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.