To determine circulating levels of adipocytokines, especially the recently characterized visfatin, and the fat-derived factor retinol-binding protein-4 (RBP-4) in HIV-infected subjects and their respective changes following treatment with highly active antiretroviral therapy (HAART). Fourteen HIV-positive, HAART-naïve subjects were compared with 10 HIV-negative healthy controls and reassessed after a 1-year treatment with HAART. Plasma visfatin and RBP-4 were determined by ELISA, whereas leptin and adiponectin by RIA. Body composition was measured with dual X-ray absorptiometry (DXA). Homeostasis model assessment (HOMA-IR) was assessed using insulin and glucose levels. Visfatin and RBP-4 levels in HIV-positive subjects were comparable with those of HIV-negative controls before treatment with HAART. Treatment with HAART for 12 months resulted in a 6.9-fold and 7.1-fold increase of visfatin and RBP-4 levels (+54.0 +/- 9.7 ng mL(-1), P < 0.0001 and +95.3 +/- 31.7 ng mL(-1), P < 0.01), respectively. Leptin (-2.7 +/- 1.6 ng mL(-1), P = 0.054) was unchanged and adiponectin (-2.8 +/- 0.7 microg mL(-1), P < 0.01) decreased. Changes of visfatin concentrations correlated significantly with the increases of RBP-4 (r = 0.78, P = 0.001), fat-free mass (FFM, r = 0.75, P < 0.05) and change of HOMA-IR (r = 0.64, P < 0.05). Parameters of glucose metabolism and body fat mass were unchanged during the observation period. Treatment with HAART induced a pronounced increase of plasma visfatin and RBP-4 as well as a decrease of adiponectin in HIV-infected patients on HAART. Although body weight, fat mass and parameters of glucose metabolism remained stable, the changes in the adipocytokines might herald subsequent alterations of these parameters.