Enhanced HIV-1 Replication in CD4+ T Cells Derived from Individuals with Latent Mycobacterium tuberculosis Infection.

BACKGROUND: Mycobacterium tuberculosis (Mtb) and HIV co-infection increases mortality, accelerates progression to AIDS, and exacerbates tuberculosis disease. However, the impact of pre-existing Mtb infection on subsequent HIV infection has not been fully explored. We hypothesized that Mtb infection creates an immunological environment that influences the course of HIV infection and investigated whether pre-existing Mtb infection impacts the susceptibility of CD4+ T cells to HIV-1 infection. METHODS: Plasma and blood CD4+ T cells isolated from HIV-negative individuals across the Mtb infection spectrum and non-Mtb-infected control individuals were analyzed for inflammation markers and T cell phenotypes. CD4+ T cells were infected with HIV-1 in vitro and were monitored for viral replication. RESULTS: We observed differences in pro-inflammatory cytokines and the relative proportion of memory T cell subsets depending on Mtb infection status. CD4+ T cells derived from individuals with latent Mtb infection supported more efficient HIV-1 transcription, release, and replication. Enhanced HIV-1 replication correlated with higher percentages of CD4+ TEM and TTD cells. CONCLUSIONS: Pre-existing Mtb infection creates an immunological environment that reflects Mtb infection status and influences the susceptibility of CD4+ T cells to HIV-1 replication. These findings provide cellular and molecular insights into how pre-existing Mtb infection influences HIV-1 pathogenesis.