Mixed-effects Models with Skewed Distributions For Time-varying Decay Rate in HIV Dynamics
Bayesian analysis, HIV longitudinal dynamics, Mixed-effects models, Skew-elliptical distribution, Time-varying viral decay rate, 62F15, 62G05, 62G09, 62N01, 62P10
Digital Object Identifier (DOI)
After initiation of treatment, HIV viral load has multiphasic changes, which indicates that the viral decay rate is a time-varying process. Mixed-effects models with different time-varying decay rate functions have been proposed in literature. However, there are two unresolved critical issues: (i) it is not clear which model is more appropriate for practical use, and (ii) the model random errors are commonly assumed to follow a normal distribution, which may be unrealistic and can obscure important features of within- and among-subject variations. Because asymmetry of HIV viral load data is still noticeable even after transformation, it is important to use a more general distribution family that enables the unrealistic normal assumption to be relaxed. We developed skew-elliptical (SE) Bayesian mixed-effects models by considering the model random errors to have an SE distribution. We compared the performance among five SE models that have different time-varying decay rate functions. For each model, we also contrasted the performance under different model random error assumptions such as normal, Student-t, skew-normal, or skew-t distribution. Two AIDS clinical trial datasets were used to illustrate the proposed models and methods. The results indicate that the model with a time-varying viral decay rate that has two exponential components is preferred. Among the four distribution assumptions, the skew-t and skew-normal models provided better fitting to the data than normal or Student-t model, suggesting that it is important to assume a model with a skewed distribution in order to achieve reasonable results when the data exhibit skewness.
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Citation / Publisher Attribution
Communications in Statistics - Simulation and Computation, v. 45, issue 2, p. 737-757
Scholar Commons Citation
Yan, Chunning; Chen, Ren; and Huang, Yangxin, "Mixed-effects Models with Skewed Distributions For Time-varying Decay Rate in HIV Dynamics" (2016). Epidemiology and Biostatistics Faculty Publications. 38.