Antiretroviral treatment induced decrease in immune activation contributes to reduced susceptibility to tuberculosis in HIV-TB co-infected persons

Antiretroviral treatment (ART) reduces the risk of developing active tuberculosis (TB) in HIV co-infected persons. We aimed to investigate the mechanisms of ART-mediated prevention of TB in HIV and TB co-infected patients on antiretroviral therapy (ART), recruited in Khayelitsha, South Africa. RNA was extracted from whole blood collected in TempusTM Blood RNA tubes at day 0 and at 1, 3 and 6 months of ART. We first performed a pilot RNAseq experiment of 12 samples (3 patients at 4 timepoints) for 50 million reads to assess if samples with lower quality and/or quantity will still yield meaningful outputs and the minimum number of reads required for sufficient coverage. This was followed by a second RNAseq experiment of 35 samples with sufficient quality: 11 from day 0 and 24 from 6 months of ART, 8 of which are paired. However, only n=6 samples from day 0 and n=6 samples from 6 months of ART could be analyzed. Results indicated reduced immune activation at 6 months of ART compared to day 0 with significant fall in the Hallmark Interferon alpha, Interferon gamma and IL-6-JAK-STAT-signalling pathway genes. These results were supported by similar changes in soluble protein markers in the plasma. Overall, our data indicates that ART- induced decrease in immune activation may contribute to reduced susceptibility to tuberculosis in HIV-TB co-infected persons. Overall design: We aimed to investigate the mechanisms of ART-mediated prevention of TB in HIV and TB co-infected patients on antiretroviral therapy (ART), recruited in Khayelitsha, South Africa. RNA was extracted from whole blood collected in TempusTM Blood RNA tubes at 0 and 6 months of ART.