Background:  The clinical presentation of leprosy is highly dependent on host cellular immunity. While there have been reports on the effect of HIV-1 infection on the manifestations of leprosy, the potential effect of M. leprae infection on HIV-1 disease pathogenesis remains unexplored. Here, we studied cellular immune parameters that are known markers of HIV-1 immunopathogenesis in patients with HIV-1/leprosy co-infection.

Methods:  We studied 28 subjects distributed in 4 groups:  HIV-1/leprosy co-infected (HL), HIV-1 mono-infected matched for viral load (H), leprosy mono-infected (L) matched for bacillary load, and healthy controls (C). Using 7-color flow cytometry to analyze peripheral blood mononuclear cells (PBMC), we evaluated naïve and memory distribution and activation status of T cells, and enumerated gdT cell and dendritic cell (DC) subsets. Groups were compared using non-parametric methods; data are reported as median [interquartile range].

Results:  CD4:CD8 T-cell ratio was decreased in both HIV-1-infected groups, but most pronounced in HL compared to controls (0.16 [0.09 to 0.20] and 1.3 [0.95 to 1.9], respectively; p <0.001)). HL subjects exhibited greater CD8⁺ T cell activation status by HLA-DR expression than HIV-monoinfected subjects and controls (MFI: 165 [94 to 271], 134 [114 to 249], and 46 [21 to 68], respectively; p <0.05). A shift from naïve and central memory to intermediate and late memory CD4⁺ T cells was demonstrated in HL, H, and L subjects compared to healthy controls. The gdT cell Vd1:Vd2 cell ratio was exaggeratedly inverted in the HL group compared with HIV-1-only subjects (HL, 30.3 [9.9 to 35.7]; H, 5.9 [3.8 to 13.7]; C, 0.63 [0.25 to 3.1]; p <0.05). No significant change in the percentage of myeloid DC was observed; however, the HIV-1-associated depression of plasmacytoid DC numbers was more marked in co-infected patients (percentage of PBMC:  HL, 0.01 [0.005 to 0.02]; H, 0.02 [0.005 to 0.18]; C, 0.13 [0.09 to 0.18]; p <0.05).

Conclusions:  Increased T cell activation, shift to late stage differentiated CD4⁺ T cells, inversion of Vd1:Vd2 ratio and loss of peripheral blood plasmacytoid DC observed in co-infected subjects together suggest that active infection with M. leprae may further exacerbate HIV-1 disease pathogenesis. This is in contrast to the apparently protective effect of this mycobacterial co-infection on simian immunodeficiency virus (SIV) disease pathogenesis in rhesus macaques. Further studies are necessary to characterize functional immune interactions between these important pathogens.