Th1 cyokines and cell activation markers in hiv and hiv-tuberculosis patients attending ampath clinic at moi teaching and refferal hospital –eldoret, kenya

Abstract

Background: Infection with HIV and TB leads to Inflammation. Markers of inflammation include TNF-α, IFN-γ, CD38 and HLA-DR. In HIV infection these markers create an environment which favours reactivation of latent TB to TB disease. TNF-α, IFN-γ, CD38, HLA-DR and CD4 cell count can be used to predict possible reactivation of latent TB to disease in HIV patients on HAART. The level of these inflammatory markers in HIV and HIV/TB co-infection in Kenya is unknown. The purpose of this study was to investigate inflammatory markers TNF-α, IFN-γ, CD38, and HLA-DR levels in patients with HIV-infection only and HIV-TB co-infected patients attending AMPATH clinic at MTRH-Eldoret, Kenya. Objective: To determine Th1 cytokine levels (TNF-α and IFN-γ) and cell activation markers (CD38 and HLA-DR) and CD4 cell count in HIV-TB co-infected and patients with HIV-infection only attending AMPATH clinic at MTRH-Eldoret, Kenya. Methods: This was a cross-sectional comparative study in which 168 patients were enrolled, 84 HIV-TB co-infected and 84 HIV patients. The patients comprised of 84 males and 84 females who had been on HAART for periods between 6 months to 10 years. Clinical and demographic information was obtained from the patients files. Blood samples from each patient were collected into EDTA tubes. Separation of plasma was done within 2 hours of sample collection at 3,000 r.p.m for 3 minutes and kept at -800C till the day of analysis. Activation markers CD38 and HLA-DR and CD4 count were analysed by flow Cytometry on whole blood samples, while analysis for the representative Th1 cytokines (TNF-α and IFN-γ) was done on the plasma samples by ELISA (Genway’s®). The levels of inflammatory markers were compared in HIV/TB co-infected patients and patients with HIV-infection only . An interview guide was the main research instrument. Data was analysed using STATA version 13. P-value ≤ 0.05 was considered significant. Results: The mean age for both HIV-TB and HIV patients was 42 years. The median (IQR) levels for TNF-α (pg/ml) was 7.26 (6.76- 8.12), IFN-γ (pg/ml) 26.3 (25.18- 27.22), CD38(%) 4.36 (2.06-6.31), HLA-DR(%) 92.44 (90.52-95.51) and CD4 (cells/mm3) 231 (117-350) in HIV-TB co-infected patients, while in HIV patients the levels were TNF-α 10.72 (8.12-12.13), IFN-γ 25.40 (23.59-27.67), CD38 5.94 (4.44-7.41), HLA-DR 93.33 (90.24-96.56) and CD4 383 (318-543). patients with HIV-infection only had higher levels of TNF-α (p=<0.001), CD38% (p=0.0002) and CD4 (p=<0.001) compared to those of TB-HIV co-infected patients. No significant difference was observed in the levels of IFN-γ and HLA-DR (p=0.1559) and (p=0.1754) respectively. Conclusion: Higher levels of TNF-α, CD38, and CD4 were found in patients with HIV-infection only compared to HIV-TB co-infected patients. This high level of inflammation may be a potential lead to TB reactivation. Recommendations: Further studies need to be done to find mechanisms which will help to control inflammation in HIV patients to lower TB reactivation. Assumptions /limitations: The only Th1 cytokines analysed were TNF-α and IFN- γ. The TNF-α and IFN-γ cytokine response was specific for HIV-TB co-infection and patients with HIV-infection only in the study subjects. Confounding factors by other infections was not considered, and this could have had some effect on the cytokine levels found.