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.

Sophie Nalukwago1, Christina L Lancioni2, Joy Baseke Oketcho1, Dave H.e Canaday3,4,
W Henry Boom3, Lonzy Ojok5, Harriet Mayanja-Kizza6
1. Joint Clinical Research Centre, Kampala, Uganda.
2. Department of Paediatric infectious diseases, Oregon Health Sciences University, Portland Oregon.
3. Division of Infectious Diseases, Case Western Reserve University.
4. Getriatric Research Center Clinical Core, Louis Stoves Cleveland VA Medicine Center.
5. Department of pathology, Makerere University College of Veterinary Medicine, Animal resources and
biosecurity, Kampala, Uganda.
6. School of Medicine, Makerere University College of Health Sciences, Mulago Hospital, Kampala, Uganda.

Abstract
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 signifcant 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 frst 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.

Keywords: Interrupted anti-retroviral treatment, memory and naive T cells, HIV patients, active pulmonary tuberculosis