Impact of tuberculosis on HIV-1 replication, diversity, and disease progression

Abstract

HIV and Mycobacterium tuberculosis not only co-circulate throughout the developing world but each has contributed to prevalence and mortality caused by the other. Several reports have described how HIV-1 increases the incidence of new M. tuberculosis infections, exacerbates the severity of tuberculosis (TB), and re-activates latent M. tuberculosis. However, the converse relationship is more difficult to understand considering TB can emerge in asymptomatic individuals and as an opportunistic infection during AIDS. Development of TB in HIV infected individuals with higher CD4 cell counts (> 200/mm3) appears to increase the rate of disease progression and mortality. Higher viral loads, increased HIV-1 diversity, and changes in cytokine/chemokine levels in HIV-infected individuals with TB appear to be related to a localized immune stimulation. Specifically, increased levels of TNF alpha and MCP-1, induced by TB, may activate HIV replication in lymphocytes, monocytes, and macrophages that are resident or have migrated to M. tuberculosis infected organs (e.g. pleura or lung). The HIV-1 found in blood following this TB-mediated burst in load and diversity appear to be phylogenetically-related to HIV-1 clones that have evolved independently in the lung or pleural compartments, now infected by M. tuberculosis.