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Background: There is an increasing prevalence of cardiovascular diseases (CVDs) and risk factors in HIV patients as the levels of AIDS-related mortality and morbidity decrease. Metabolic syndrome (MetS) is the accumulation of various CVD risk factors that predict the occurrence of CVDs. We investigated the prevalence of MetS and associated risk factors in HIV patients treated with combination antiretroviral therapy (cART), cART-naïve HIV patients, and non-HIV controls., Methods: In a case-control design, 158 cART-treated HIV patients, 150 cART-naïve HIV patients, and 156 non-HIV controls were recruited from a periurban hospital in Ghana. A structured questionnaire was used to collect data on demography, lifestyle, and medication. Anthropometric indices and blood pressure were measured. Fasting blood samples were collected to measure the plasma levels of glucose, lipid profile, and CD4+ cells. The presence of MetS was defined using the joint scientific statement criteria., Results: The prevalence of MetS was higher in cART-treated HIV patients compared with cART-naïve HIV patients and non-HIV controls (57.3% vs. 23.6% vs. 19.2% and p < 0.001, respectively). MetS was associated with cART-treated HIV patients (odds ratio (95% CI) = 7.24 (3.41-15.39) and p < 0.001), cART-naïve HIV patients (2.04 (1.01-4.15), p =0.048), and female gender (2.42 (1.39-4.23) and p =0.002). In cART-treated HIV patients, those on zidovudine (AZT)-based regimens were associated with increased likelihood (3.95 (1.49-10.43) and p < 0.006), while those on tenofovir (TDF)-based had decreased likelihood (0.32 (0.13-0.8) and p =0.015) of having MetS., Conclusion: In our study population, there was a high prevalence of MetS in cART-treated HIV patients compared to cART-naïve HIV patients and non-HIV controls. HIV patients on AZT-based regimens had an increased likelihood of having MetS, while those on TDF-based regimens had a reduced likelihood of having MetS., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2023 Bartholomew Dzudzor et al.)