The Effects of HIV-1 Infection on Latent Tuberculosis

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, weexamine the impact that HIV-1 infection has on persons with latent tuberculosis. Based on previouswork, we develop a mathematical model of an adaptive immune response in the lung whichconsiders relevant immune effectors such as macrophages, various sub-populations of T-cells, andkey cytokines to predict which mechanisms are important to HIV-1 infection induced reactivationof tuberculosis. Our results indicate that persons latently infected with TB who are subsequentlyco-infected with HIV-1 will suffer reactive TB. The mechanisms that contribute to this are essentiallyrelated to a completely different cytokine environment at the onset of HIV-1 infection dueto the presence of Mycobacterium tuberculosis. Our analysis suggests that macrophages play animportant role during co-infection and decreases in macrophage counts are coupled to a decline inCD4⁺ T-cells and increased viral loads. These mechanisms are also coupled to lower recruitmentof T-cells and macrophages, compromising protective immunity in the lung and eventually leadingto TB reactivation. These results point to potential targets for drug and vaccine therapies.