Date Published: December , 2017
Publisher: Makerere Medical School
Author(s): Sophie Nalukwago, Christina L Lancioni, Joy Baseke Oketcho, Dave H e Canaday, W Henry Boom, Lonzy Ojok, Harriet Mayanja-Kizza.
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.
To ascertain the effect of interrupted ART on reconstitution of CD4+ and CD8+ T sub-sets in TB patients.
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.
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.
Interrupting ART alters CD8+ but not CD4+ sub-sets in patients with less advanced HIV infection and TB.
One in every four of human immunodeficiency virus type-1 (HIV-1) infected persons in the world is diagnosed with active pulmonary tuberculosis (TB)1. Tuberculosis accelerates progression of HIV infection to acquired immune deficiency syndrome (AIDS) compared to HIV patients without TB2,3. In Uganda at least 39% of TB cases in adults are complicated with HIV infection which poses a risk of high fatality rates4.
Seventy six HIV-1 infected participants of whom thirty nine received ART with concurrent TB treatment and 37 received TB treatment alone, were analysed. Demographic baseline characteristics of the two groups did not significantly differ from each other (Table 1).
In the majority of chronically HIV-infected individuals left untreated, depletion of CD4+ T cells, changes in distribution and function of T cell sub-populations and alterations in CD4:CD8 T cell ratios are some of the consequences of uncontrolled viral replication. This is made worse in HIV/TB co-infected patients with TB driving immune activation which enhances viral replication. Upon administration of effective anti-retroviral therapy and TB treatment in HIV-TB patients, the peripheral T cells increase and alterations of some T cell sub-populations occur16,17. In this prospective cohort study of the effect of interrupted ART on T cell sub-sets during treatment of active pulmonary tuberculosis among HIV infected patients with CD4+ cell counts of > 350 cells/µL, we observed that ART administered concurrently with TB treatment causes a significant increase in naive CD8+ T cells. The ART intervention increased the proportion of naive CD8+ T cells during 6 months of treatment and this proportion declined close to baseline values when ART was withdrawn. We also report that during the 6 months of intervention, the effector memory CD8+ T cells decreased significantly. In the TB treatment alone arm, after 6 months of treatment, we observed a significant increase in naive CD8+ T cells. T cell sub-population reconstitution has been a subject of interest in HIV and TB infections for long time in research; however, most studies have been limited by focusing on either HIV or TB infection17,18,19. This study is one of its kind that focuses on dual infections.
Our analysis in this study provides more insight in the reconstitution of T cell sub-populations in HIV-TB infected patients with high CD4+ T cell counts. Although initially, this study was not designed with a systematic ART interruption model, interruption of ART did not yield immunological benefits which suggest poor clinical outcomes to the patients.