Issue Math. Model. Nat. Phenom. Volume 3, Number 7, 2008 Special issue dedicated to Glenn Webb Page(s) 229 - 266 DOI 10.1051/mmnp:2008051 Published online 23 October 2008

Math. Model. Nat. Phenom. Vol. 3, No. 7, 2008, pp. 229-266
DOI: 10.1051/mmnp:2008051

The Effects of HIV-1 Infection on Latent Tuberculosis

Amy L. Bauer^{1, 2}, Ian B. Hogue³, Simeone Marino³ and Denise E. Kirschner<sup>3

1</sup>  Theoretical Division, Los Alamos National Laboratory, Los Alamos, New Mexico, 87545, USA
²  Department of Mathematics, University of Michigan, Ann Arbor, Michigan, 48109, USA
³  Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, Michigan, 48109, USA

kirschne@umich.edu

Published online: 23 October 2008

Abstract
Tuberculosis is the leading cause of death due to infectious diseases in the world today, and it is increasing due to co-infection with HIV-1, the causative agent of AIDS. Here, we examine the impact that HIV-1 infection has on persons with latent tuberculosis. Based on previous work, we develop a mathematical model of an adaptive immune response in the lung which considers relevant immune effectors such as macrophages, various sub-populations of T-cells, and key cytokines to predict which mechanisms are important to HIV-1 infection induced reactivation of tuberculosis. Our results indicate that persons latently infected with TB who are subsequently co-infected with HIV-1 will suffer reactive TB. The mechanisms that contribute to this are essentially related to a completely different cytokine environment at the onset of HIV-1 infection due to the presence of Mycobacterium tuberculosis. Our analysis suggests that macrophages play an important role during co-infection and decreases in macrophage counts are coupled to a decline in CD4⁺ T-cells and increased viral loads. These mechanisms are also coupled to lower recruitment of T-cells and macrophages, compromising protective immunity in the lung and eventually leading to TB reactivation. These results point to potential targets for drug and vaccine therapies.

Mathematics Subject Classification. 92D25

Key words: HIV -- Mycobacterium tuberculosis -- macrophages -- uncertainty analysis -- sensitivity analysis -- mathematical model -- immunology

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