HIV-infected children and adolescents may be at risk for cardiovascular disease due to chronic inflammation and exacerbation of risk factors. The aim of this study was as follows: 1) compare cardiovascular risk factors, chronic inflammation, and carotid intima-media thickness (IMTc) between the HIV and control groups; 2) determine the association of HIV and antiretroviral (ART) regimens with cardiovascular risk factors, chronic inflammation, and IMTc; and 3) identify variables associated with elevated IMTc. Cross-sectional analysis of 130 children and adolescents, 8–15 years of age, divided into HIV-infected (n = 65) and healthy control (n = 65) participants. Body fat, blood pressure, glycemia, insulin, and glycated hemoglobin, total cholesterol and fractions (LDL-C and HDL-C), triglycerides, C-reactive protein (CRP), interleukin (IL)-6, tumor necrosis factor-alpha (TNF-α), and the IMTc were measured. The results showed HIV-infected children and adolescents had higher levels of glycemia (87.9 vs. 75.9 mg.dL−1, p< 0.001), LDL-c (94.7 vs. 79.5 mg.dL−1, p = 0.010), triglycerides (101.2 vs. 61.6 mg.dL−1, p< 0.001), CRP (1.6 vs. 1.0 mg.L−1, p = 0.007), IL-6 (1.42 vs. 0.01 pg.mL−1, p< 0.001), TNF-α (0.49 vs. 0.01 pg.mL−1, p< 0.001), mean IMTc (0.526 vs. 0.499 mm, p = 0.009), and lower HDL-c (53.7 vs. 69.4 mg.dL−1, p< 0.001) compared to controls. Systolic blood pressure (β = 0.006, p = 0.004) and TNF-α (β = −0.033, p = 0.029) accounted for 16% of IMTc variability in HIV-infected children and adolescents. In patients using protease inhibitors-based ART, male gender (β = −0.186, p = 0.008), trunk body fat (β = −0.011, p = 0.006), glucose (β = 0.005, p = 0.046), and IL-6 (β = 0.017, p = 0.039) accounted for 28% of IMTc variability. HIV-infected children and adolescents may be at risk for premature atherosclerosis due to chronic inflammation and dyslipidemia. Interventions with the potential to improve lipid profile, mitigate inflammation, and reduce cardiovascular risk are needed.