The Effect of Antiretroviral Therapy on SIRT1, SIRT3 and SIRT6 Expression in HIV-Infected Patients

Abstract

Human Immunodeficiency Virus (HIV) infection and the chronic use of combined antiretroviral therapy (cART) may affect the occurrence of certain disturbances in the body. There is growing interest in sirtuins–enzymes involved in the regulation of many metabolic processes in the organism and in the pathogenesis of many diseases which also exhibit potential antiviral activity. The aim of the study was to investigate the connection of cART to the expression of Sirtuin 1 (SIRT1), Sirtuin 3 (SIRT3) and Sirtuin 6 (SIRT6) in HIV-infected men. The plasma levels of sirtuins were measured before and one year after cART, and related to HIV viral load, lymphocytes T CD4+ and CD8+ count as well as the applied cART. The levels of sirtuins in plasma were measured in HIV-infected patients (n = 53) and the control group (n = 35) by immunoassay methods. There were statistically significant (p < 0.05) differences between SIRT6 in the HIV-infected patients before therapy and in the subgroups, depending on the count of lymphocytes T CD8+. There were significant differences in the levels of SIRT1 depending on the applied treatment regimen. The obtained results indicate the most significant changes in the expression of SIRT6 in the course of HIV infection and suggest an influence of the type of cART on the level of SIRT1, which indicates its important role in the course of HIV.

Sirtuin 1 in Host Defense during Infection

“…The SIRT1 activator resveratrol induces SIRT1 mRNA in PBMCs and decreases Per2-expressing HPCs in HIV+ patients [ 72 ]. During combined antiretroviral treatment in HIV infection, the plasma SIRT1 level is higher in patients treated with integrase transfer inhibitors than in to those treated with protease inhibitors [ 73 ]. These data suggest a significantly diminished SIRT1 level in HIV patients and that SIRT1 is differentially regulated depending on the treatment regimen.…”