Background: Mycobacterium tuberculosis has been shown to enhance antibody responses against diverse viruses, potentially via the impact of lipid antigens or trained immunity. We hypothesized that active tuberculosis (TB) enhances the development of HIV-1 neutralizing antibodies in HIV-1 co-infection. Methods: We compared anti-HIV-1 antibody responses among treatment- naive plasma samples from 15 HIV-1 participants with TB (HIV- 1/TB) and 16 HIV-1 participants without TB. Ability to inhibit 12 different tier 1 and 2 HIV-1 variants of diverse subtypes in the TZM-bl neutralization assay was used to estimate a neutralization breadth and potency (BP) score. ELISA was used to compare antibody titers against other latent infections. Results: HIV-1/TB and HIV-1 infected participants had similar baseline plasma virus levels (p = 0.33) and CD4 counts (p = 0.40). HIV-1/ TB individuals had a significantly higher BP score (0.57 ± 0.05, range 0.32 to 0.97) than HIV-1 group (0.41 ± 0.05, range 0.24 to 0.57, p = 0.02). The plasma activity of 6 HIV-1/TB individuals with high baseline BP scores clustered with CD4 binding site and membraneproximal external region targeting broadly neutralizing antibodies (bnAbs). After completing TB treatment and/or starting HIV-1 therapy for 6 months, HIV-1/TB (0.64 ± 0.09, n = 6, range 0.22 to 0.99) as compared to HIV-1 participants (0.48 ± 0.09, n = 8, range 0.26 to 0.78) still had higher neutralizing capacity, but the difference was not statistically significant (p = 0.11). Neutralization BP score did not correlate with the total plasma IgG, baseline viral load, CD4 count, IL-6, sCD163, and MCP-1 concentrations. HIV-1/TB (0.02 ± 0.01) as compared to HIV-1 (0.03 ± 0.01; p = 0.68) group had similar level of HIV-1 envelope diversity. The HIV-1/TB and HIV-1 only participants had similar anti-tetanus (p = 0.44) and anti-HSV (p = 0.25) antibody titers. Conclusions: Our results suggest that active TB enhances the neutralizing capacity of anti-HIV-1 antibodies, possibly leading to the emergence of bnAbs that target conserved envelope domains. TB neither potentiates pre-existing antibody responses against latent infections nor correlates with other factors previously shown to be important for bnAb emergence. Mechanisms that account for the enhanced HIV-1 neutralization in HIV-1 individuals with active TB could be leveraged in the generation of a more effective humoral response in HIV-1 vaccination and treatment.
