To determine whether the clinical and metabolic features associated with nonalcoholic fatty liver disease (NAFLD) are similar between HIV-positive and HIV-negative male subjects. Twenty-six HIV-positive and 25 HIV-negative subjects with liver biopsy-proven NAFLD were compared for liver histology (extent of steatosis, steatosis grading, and fibrosis staging), blood biochemistry (glucose, insulin, C-peptide, hemoglobin A1c, and lipid profile), insulin resistance (IR) using a homeostasis model assessment, anthropometry (body mass index [BMI], waist circumference, and arm muscle area), dietary intake, and physical activity. The 2 groups were similar for age, liver histology, and IR. HIV-positive patients had a lower BMI (26.3 +/- 0.5 vs. 30.2 +/- 1.0 kg/m; P = 0.001) and lower percentage of fat mass (19.4 +/- 0.9 vs. 22.7 +/- 1.2; P = 0.026) when compared with HIV-negative patients. Although caloric intake was similar between groups, HIV-positive patients had a higher physical activity level (8.3 +/- 1.6 vs. 4.1 +/- 0.8 units of exercise per day; P = 0.029). Blood triglycerides were significantly higher (3.14 +/- 0.39 vs. 1.86 +/- 0.20 mmol/L; P = 0.006) in HIV-positive patients. Although NAFLD was similar between the 2 groups, HIV-positive patients had a lower BMI and were more physically active compared with HIV-negative patients. This may suggest that in HIV, NAFLD is associated with factors other than those related to body fatness, such as HIV infection and treatment.