Hierarchical Bayesian methods for estimation of parameters in a longitudinal HIV dynamic system.

TitleHierarchical Bayesian methods for estimation of parameters in a longitudinal HIV dynamic system.
Publication TypeJournal Article
Year of Publication2006
AuthorsHuang Y, Liu D, Wu H
JournalBiometrics
Volume62
Issue2
Pagination413-23
Date Published2006 Jun
ISSN0006-341X
KeywordsAntiretroviral Therapy, Highly Active, Bayes Theorem, Biometry, HIV Infections, HIV-1, Humans, Longitudinal Studies, Models, Biological, Models, Statistical, Randomized Controlled Trials as Topic
Abstract

HIV dynamics studies have significantly contributed to the understanding of HIV infection and antiviral treatment strategies. But most studies are limited to short-term viral dynamics due to the difficulty of establishing a relationship of antiviral response with multiple treatment factors such as drug exposure and drug susceptibility during long-term treatment. In this article, a mechanism-based dynamic model is proposed for characterizing long-term viral dynamics with antiretroviral therapy, described by a set of nonlinear differential equations without closed-form solutions. In this model we directly incorporate drug concentration, adherence, and drug susceptibility into a function of treatment efficacy, defined as an inhibition rate of virus replication. We investigate a Bayesian approach under the framework of hierarchical Bayesian (mixed-effects) models for estimating unknown dynamic parameters. In particular, interest focuses on estimating individual dynamic parameters. The proposed methods not only help to alleviate the difficulty in parameter identifiability, but also flexibly deal with sparse and unbalanced longitudinal data from individual subjects. For illustration purposes, we present one simulation example to implement the proposed approach and apply the methodology to a data set from an AIDS clinical trial. The basic concept of the longitudinal HIV dynamic systems and the proposed methodologies are generally applicable to any other biomedical dynamic systems.

DOI10.1111/j.1541-0420.2005.00447.x
Alternate JournalBiometrics
PubMed ID16918905
PubMed Central IDPMC2435289
Grant ListR01 AI052765 / AI / NIAID NIH HHS / United States
R01 AI055290 / AI / NIAID NIH HHS / United States
R01 AI055290 / AI / NIAID NIH HHS / United States
U01 AI27658 / AI / NIAID NIH HHS / United States