The Effects of HIV-1 Infection on Latent Tuberculosis

¹ 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

Corresponding author: kirschne@umich.edu

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.