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Background: HIV infection is characterized by progressive depletion of CD4 + T cells due to their reduced synthesis and increased destruction followed by marked activation and expansion of CD8 + T lymphocytes. CD4/CD8 ratio was traditionally described as a marker of immune system ageing in the general population, but it increasingly appears as a marker of different outcomes in the HIV-infected population. The main objective of this study is to examine the power of CD4/CD8 ratio in predicting the occurrence of metabolic syndrome (MetS) in HIV-positive patients receiving cART therapy. Methods: 80 HIV/AIDS subjects were included in a retrospective case-control study. Flow cytometry was used to determine the percentage of CD4 + and CD8 + cells in peripheral blood of these patients. The values of biochemical parameters (triglycerides, HDL, blood sugar, blood counts), immunological parameters (CD4/CD8, PCR), anthropometric measurements and type of cART therapy were evaluated in this study. Results: After six months of cART therapy 19 (23.8%) subjects had all the elements necessary for making the diagnosis of MetS. Using multivariate analysis CD4/CD8 ratio was statistically significant (p < 0.05) and had the largest effect on development of MetS (Wald = 9.01; OR = 0.45), followed by cART (Wald = 7.87; OR = 0.10) and triglycerides (Wald = 5.27; OR = 1.7). On the other hand, body weight and waist circumference showed no statistically significant effect on the development of MetS after six months of cART, p > 0.05. Conclusions: CD4/CD8 ratio proved to be a significant marker for prediction of metabolic syndrome in HIV/AIDS patients