Impact of antiretroviral and tuberculosis therapies on CD4+ and CD8+ HIV/M. tuberculosis-specific T-cell in co-infected subjects

Abstract

Background: Human Immunodeficiency Virus (HIV) infection is a risk factor for tuberculosis (TB). Antiretroviral therapy (ART) changed HIV clinical management but it is still unclear how pre-existing HIV/Mycobacterium tuberculosis (Mtb)-specific CD4⁺ and CD8⁺ T-cells are restored.

Aim: to evaluate the impact of ART and TB therapies on the functional and phenotypic profile of Mtb-specific antigen-response of CD4⁺ and CD8⁺ T-cells in prospectively enrolled HIV-TB co-infected patients.

Methods: ART-naïve HIV-infected patients, with or without active TB or latent TB infection (LTBI), were enrolled before and after starting ART and TB therapies. Peripheral blood mononuclear cells (PBMC) were stimulated overnight with Mtb and HIV antigens (GAG). Cytokine expression and phenotype profile were evaluated by flow cytometry. Cytomegalovirus (CMV) and staphylococcal enterotoxin B (SEB) were also used.

Results: The median of absolute number of CD4⁺ T-cells increased after ART and TB therapies in all groups analyzed, while the median of absolute number of CD8⁺ T-cells decreases in HIV and HIV-LTBI groups. Treatments significantly increased the frequency of Mtb-specific CD4⁺ T-cells in the HIV-LTBI (p = 0.015) with a rise of the central memory compartment. The magnitude of the CD4⁺ T-cell response to HIV-GAG significantly increased in active TB (p = 0.03), whereas the magnitude of CMV-specific CD4⁺ T-cell response decreased in all the groups. Similarly, the treatments increased the number of Mtb-specific CD8⁺ responders in both HIV-LTBI and HIV-TB groups, whereas the phenotype distribution was dependent on the antigens used and on the stage of infection/disease.

Conclusions: After therapies the median of absolute number and the proportion of CD4⁺ T-cells increased in all groups whereas the median of absolute count and proportion of CD8⁺ T-cells decreased in the HIV and HIV-LTBI subjects. Interestingly, an increased frequency of CD4⁺ T-cell response to RD1 proteins in HIV-LTBI subjects was found. These results contribute to a better understanding of the effect of ART and TB therapies on the modulation of Mtb-specific CD4⁺ and CD8⁺ T-cells subsets.

Keywords: ART; CD4(+) T-cells; CD8(+) T-cells; HIV; Tuberculosis; Tuberculosis therapy.