The Annals of Applied Statistics

Modeling the dynamics of biomarkers during primary HIV infection taking into account the uncertainty of infection date

J. Drylewicz, J. Guedj, D. Commenges, and R. Thiébaut

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Abstract

During primary HIV infection, the kinetics of plasma virus concentrations and CD4+ cell counts is very complex. Parametric and nonparametric models have been suggested for fitting repeated measurements of these markers. Alternatively, mechanistic approaches based on ordinary differential equations have also been proposed. These latter models are constructed according to biological knowledge and take into account the complex nonlinear interactions between viruses and cells. However, estimating the parameters of these models is difficult. A main difficulty in the context of primary HIV infection is that the date of infection is generally unknown. For some patients, the date of last negative HIV test is available in addition to the date of first positive HIV test (seroconverters). In this paper we propose a likelihood-based method for estimating the parameters of dynamical models using a population approach and taking into account the uncertainty of the infection date. We applied this method to a sample of 761 HIV-infected patients from the Concerted Action on SeroConversion to AIDS and Death in Europe (CASCADE).

Article information

Source
Ann. Appl. Stat., Volume 4, Number 4 (2010), 1847-1870.

Dates
First available in Project Euclid: 4 January 2011

Permanent link to this document
https://projecteuclid.org/euclid.aoas/1294167801

Digital Object Identifier
doi:10.1214/10-AOAS364

Mathematical Reviews number (MathSciNet)
MR2829938

Zentralblatt MATH identifier
1220.62133

Keywords
Dynamical model nonlinear models ordinary differential equations HIV dynamics primary infection

Citation

Drylewicz, J.; Guedj, J.; Commenges, D.; Thiébaut, R. Modeling the dynamics of biomarkers during primary HIV infection taking into account the uncertainty of infection date. Ann. Appl. Stat. 4 (2010), no. 4, 1847--1870. doi:10.1214/10-AOAS364. https://projecteuclid.org/euclid.aoas/1294167801


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