Plasma indoleamine 2,3-dioxygenase activity is associated with the size of HIV reservoir in patients receiving antiretroviral therapy.

Background: Indoleamine 2, 3-dioxygenase (IDO) is an immunoregulatory enzyme that metabolises tryptophan to immunosuppressive kynurenines. We investigated whether IDO activity is associated with the size of HIV reservoirs.

Methods: In this cross-sectional study, total HIV DNA in PBMCs from 127 HIV-infected patients receiving antiretroviral therapy (ART) was quantified. Tryptophan and kynurenine concentrations, as well as microbial translocation markers were measured in plasma samples. T cell activation (HLA-DR, CD38) and exhaustion (programmed cell death-1 (PD-1)) in PBMC were assessed by flow cytometry.

Results: Elevated IDO activity prior to ART correlated with on-ART HIV DNA (r=0.35, P=0.004), but was not associated with pre-ART HIV DNA. A median duration of 15 months of ART significantly decreased IDO activity from the pre-ART levels; however, these levels were still higher than those observed in HIV-uninfected controls. Among treated participants, IDO activity positively correlated with their concurrent HIV DNA (r=0.36, P<0.0001). Multivariate model showed an independent association of pre-ART CD4/CD8 ratio (adjusted Odds ratio (aOR) =0.75 per 0.1 increase, 95% confidential intervals (CI): 0.62-0.91) and on-ART IDO activity (aOR=1.09 per nM/μM increase, 95%CI: 1.04-1.14) with higher levels of HIV DNA on-ART. A lack of association of the microbial translocation markers was observed with the size of HIV reservoir. Among treated participants, HIV DNA positively correlated with the proportions of activated CD4 T and CD8 T cells and exhausted CD4 T cells.

Conclusions: We observed a positive correlation between IDO activity and total HIV DNA in blood, highlighting the important role of immunometabolic aberrations in HIV persistence.