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Background: Antiretroviral therapy (ART) improved the prognosis of people living with human immunodeficiency virus (HIV) (PLWH). Life-long treatment is required in PLWH and is accompanied by various metabolic abnormalities in the disease course. Data about the epidemiology and the dynamic changes of dyslipidemia in PLWH receiving antiretroviral therapy were scarce in Asian countries. This study aimed to explore the risk factors of dyslipidemia and analyze the longitudinal changes of dyslipidemia among Chinese PLWH receiving HAART. Methods: We conducted a longitudinal analysis of PLWH enrolled in two large multicenter clinical trials across China, and outpatients followed at the clinic of Peking Union Medical College Hospital. Demographic data and clinical parameters were collected. The risk factors and longitudinal changes in lipid profiles associated with HIV-1 infection were analyzed. The definition of dyslipidemia was made based on the National Cholesterol Education Program, Adult Treatment Panel (NCEP-ATP) III guidelines. Results: A total of 1542 PLWH were included. The median follow-up was 6 years. At baseline, the concentrations of total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) were 4.1 ± 0.91 mmol/L, 1.2 (interquartile ranges [IQR] 0.85–1.75) mmol/L, 1.1 ± 0.37 and 2.4 ± 0.76 mmol/L, respectively. The rate of hypercholesterolemia, hyperglyceridemia, high LDL-C, and low HDL-C were 10.18%, 26.39%, 9.08%, and 44.94%, respectively. The overall prevalence of dyslipidemia was 69.3%, which raised to 84.3% after antiretroviral therapy, substantially higher. CD4/CD8 ratio < 0.3 and viral load > 105 copies/mL were risk factors associated with any subtype of dyslipidemia. A negative correlation between CD8+CD38+ percentage and HDL-C concentration was found. The regimens including efavirenz (EFV) and tenofovir (TDF) showed better lipid profiles. Longitudinal analysis revealed that both the level and the percentage of abnormal TG and HDL-C occurred drastic change in the first 6 months after ART initiation (from 4.07 to 4.41, from 1.11 to 1.28mmol/L, from 26.39 to 31.1% and from 44.94 to 29.5%, respectively). Conclusions: The prevalence of dyslipidemia is high in PLWH and increases after ART, mainly represented as high TG and low HDL-C and associated with advanced stage of HIV-1 infection. The greatest changes in lipids occurred in the early stage after initiating ART therapy. The results suggest that dyslipidemia should be monitored and managed when starting ART. [ABSTRACT FROM AUTHOR]