The Effects of HIV-1 Infection on Latent Tuberculosis

Abstract

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.

Epidemiological models of Mycobacterium tuberculosis complex infections

“…This suggests that the presence of MTBC in the HIV-infected individuals weakens the immune system. Another model by Bauer et al shows that the decline in the number of T-cells in HIV/TB co-infected patient leads to latent TB reactivation and more rapid progression to active TB [93]. …”

Modelling HIV and MTB Co-Infection Including Combined Treatment Strategies

“…Such models have been developed for various aspects of HIV infection [11]–[27] and for MTB infection [28]–[38]. Only a few [39]–[42] have been developed for HIV-MTB co-infection. Of the latter the earliest [40] has four populations: T cells (CD4+ and CD8+ combined), macrophages, HIV and MTB.…”

Surface Energetic Effects of Human Immunodeficiency Virus Co-Infection on Mycobacterium Tuberculosis-Macrophage Interaction Mechanism

“…+ T-cells and macrophages are critical to our immune system response and HIV is a virus that specially infects them [1], thus compromising the host ability to control interaction(s). HIV weakens the immune system; tb thrives in a weakened immune system.…”

“…In the world today, tuberculosis (tb) is the leading cause of death due to its interaction with other infectious diseases such as the Human Immunodeficiency Virus (HIV), which is the AIDS causative agent [1]. The HIV impact on tb is quite overwhelming prior to the fact that tb would already be declining worldwide if not for HIV which is contributing approximately 10% of all global mortality cases [2].…”

“…The bacterial pathogen that causes tb mycobacterium tuberculosis (mtb) latently infects one third of the world's population and is responsible for the highest mortality rate of any single bacterial pathogen [3,4]. The lung is typically the primary site of the bacterial infection, where it is engulfed by macrophages during an innate immune response [1]. Mycobacterium tb has a slow doubling time of about 15-20 hours, and prefers to live within macrophages.…”