Value and cost analysis of CD38+ cd4 and CD8 T lymfocytes in the evaluation of response to treatment in previously untreated HIV i̇nfected patients

Objective: Immune activation by B, T (CD4, CD8) and NK cells plays an important role in the pathogenesis of human immunodeficiency virus (HIV) infection, and the most important indicators of this are the increased expression of CD38 and HLA-DR molecules on CD8+ and CD4+ T lymphocytes. The gold standard in monitoring the efficacy of antiretroviral treatment in patients with HIV infection is HIV-RNA determination by rt-PCR method together with CD4+ T cell count. However, because high cost and relatively long reporting time of HIV-RNA test, there is still a need for inexpensive, rapid and reliable monitoring test. The aim of this study is to determine the value of CD38+ and HLA-DR+ T lymphocyte ratios in the evaluation of the efficacy of antiretroviral therapy in patients with HIV infection. Materials and Methods: In this prospective study, patients who were found to be HIV (+) and planned to start antiretroviral therapy between 30 May 2019 and 15 June 2020 in the Infectious Diseases and Clinical Microbiology clinic of Çukurova University Faculty of Medicine were included. These patients were evaluated before the treatment, at the 3rd and 6th months after the start of treatment, and the ratio of CD38+ and HLA-DR+ T lymphocytes in the blood samples taken in addition to the tests used in routine follow-up was determined by flow cytometry (Beckman Coulter Navios, USA). These results were compared with the CD4+ T lymphocyte count and HIV-RNA level used for routine follow-up, and the role of CD38+ and HLA-DR+ T lymphocyte ratios in monitoring the effectiveness of antiretroviral therapy was investigated. Results: Of the 59 newly diagnosed patients included in the study, 56 (95%) were male, and the mean age was 34.4±11.6 (18-68). The test results of the patients before the treatment, at the 3rd month and 6th month after the treatment were evaluated statistically. HIV-RNA mean pre-treatment was 615123.78 copies/ml, post-treatment 9410.80 copies/ml at 3 months, 35671.73 copies/ml at 6 months; The mean CD4+ T lymphocyte count was 363.39 cell/mm3 before the treatment, 595.23 cell/mm3 at the 3rd month after the treatment, 683.51 cell/mm3 at the 6th month; The mean CD38+ T lymphocyte rate was 48.3% before the treatment, 28.3% at the 3rd month of the treatment, 27.7% at the 6th month; The mean HLA-DR+ T lymphocyte ratio was 36.3% before the treatment, 28.5% at the 3rd month of the treatment, and 22.8% at the 6th month. When the CD38+ T lymphocyte ratio was examined in patients who were started on antiretroviral therapy, it was found that there was a statistically significant decrease in the 3rd and 6th months compared to the pre-treatment period (p<0.01), but the decrease between the 3rd and 6th months was not statistically significant (p). >0.05). A correlation was found between pre-treatment and 3rd month and between 3rd and 6th month values in HLA-DR+ T lymphocyte ratios (p<0.01). During the study, it was investigated whether there was a correlation between CD38+ T lymphocyte ratio and HIV-RNA level, CD4+ T lymphocyte count and HLA-DR+ T lymphocyte ratio. When the CD38+ T lymphocyte ratio and HIV-RNA values were compared, a significant positive correlation was found before the treatment (p<0.01), but no correlation was found at the 3rd and 6th months of the treatment (3rd month p=0.389 ; 6th month p=0.360). There was a negative correlation between CD38+ T lymphocyte ratio and CD4+ T lymphocyte count throughout the study (pre-treatment p<0.01; 3rd month p<0.01 ; 6th month p<0.05). A significant positive correlation was found between CD38+ T cell ratio and HLA-DR+ T cell ratio only at 3 months (p<0.05). Discussion and conclusions: The results obtained in this study suggest that the CD38+ T lymphocyte ratio and the HLA-DR+ T lymphocyte ratio can be used to evaluate the efficacy of antiretroviral therapy in patients with HIV infection. The findings are promising as low-cost and rapid alternatives to these tests, which can be performed on a blood sample for CD4+ T cell count. Longer-term studies with larger patient groups are needed to confirm the findings.