Based on their characteristics, we hypothesized that the following parameters, namely collagen IV, glutathione S-transferase, secretory component (SC), and AMP-activated protein kinase alpha 1 alpha 2 may be useful serum markers in the detection of comorbidities in treated HIV-infected patients. These parameters were determined in 204 HIV-infected patients and 35 controls by using IEF and densitometry. Collagen IV was undetectable in controls and the majority of HIV-infected patients. Twenty-two HIV-infected patients presented significantly elevated levels of collagen IV, most of them were coinfected with hepatitis C virus and/or hepatitis B virus. SC was undetectable in controls. SC was significantly increased in 81 HIV-infected patients and significantly correlated with aspartate aminotransferase (r = 0.267, p = 0.0049), alkaline phosphatase (r = 0.309, p = 0.0011), and gamma-glutamyl-transferase (r = 0.264, p = 0.0054). Glutathione S-transferase levels of HIV-infected patients were significantly higher than the controls (3779 +/- 5860 vs. 785 +/- 71 DU, p = 0.0007) and significantly correlated with serum urea (r = 0.204, p = 0.0038), triglycerides (r = 0.209, p = 0.0033), and lipase (r = 0.219, p = 0.0025). AMP-activated protein kinase alpha 1 alpha 2 levels of HIV-infected patients were significantly higher than the controls (5676 +/- 6248 vs. 1189 +/- 6248 DU, p = 0.0009). Further studies are needed to demonstrate the relevance of these results to diagnose non-AIDS-related illnesses in HIV-infected patients.