The Effects of HIV–1 Infection on Latent Tuberculosis

Abstract

Tuberculosis is the leading cause of death due to infectious diseases in the world to- day, 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 previ- ous 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 essen- tially 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.