The effect of interrupted anti-retroviral treatment on the reconstitution of memory and naive T cells during tuberculosis treatment in HIV patients with active pulmonary tuberculosis

Background: The reconstitution of cellular immune components contributes to clinical outcome of HIV and Mycobacterium tuberculosis (MTB) infection. Interruption of anti-retroviral therapy (ART) could lead to perturbations in reconstitution of T cells in HIV/ tuberculosis (TB) patients. Objectives: To ascertain the effect of interrupted ART on reconstitution of CD4⁺ and CD8⁺ T sub-sets in TB patients. Methods: Participants with HIV (CD4>350 cells/µL) and TB were recruited under a larger phase 3 open label randomised controlled clinical trial. The CD45RO and CD62L markers were measured on CD4⁺ and CD8⁺ cells by flow cytometry. Samples were analysed at baseline, 3, 6, 12 months. Results: There was a significant increase of naive CD8⁺ cells (p = 0.003) and a decrease in effector CD8⁺ cells (p = 0.004) among participants in ART/TB treatment arm during the first 6 months. Withdrawing ART led to naive CD8⁺ cells reduction (p=0.02) to values close to baseline. An increase of naive CD8⁺ cells after 6 months of TB treatment in TB alone treatment arm (p=0.01) was observed. A trend towards increment of naive CD4⁺ sub sets in either treatment arms was observed. Conclusion: Interrupting ART alters CD8⁺ but not CD4⁺ sub-sets in patients with less advanced HIV infection and TB.