OBJECTIVES: The study objective was to evaluate the impact of renal-, cardiometabolic- and bone-related comorbidities on health care resource utilization and costs in HIV-positive patients, using the Quebec (RAMQ) public drug plan database. METHODS: Patients who had received antiretroviral treatment for at least six months from January 2006 to June 2012 were selected. HIV-positive patients with no comorbidities were matched 1:1 for age, sex and time of follow-up and compared to HIV-positive patients with at least one comorbidity. Index date was defined as the date of the first medication, diagnosis or medical procedure related to comorbidities for the patient with at least one comorbidity, and the corresponding date of the case was defined for the controls. Cases and controls were compared with independent t-test for continuous variables and chi-square test for categorical variables. RESULTS: For the analysis of 1,336 HIV-positive patients with at least one renal-, cardiometabolic- or bone-related comorbidity and a matched control group of 1,336 HIV-positive patients with no comorbidities, the mean age was 45.1 years (SD=9.5) with 78.5% being male. The mean total health care cost per patient per year in the 2 years following index date was higher in HIV-positive patients with at least one comorbidity than in HIV-positive patients with no comorbidities (22,037 CAN$ SD=16,974 vs. 15,093 CAN$ SD=8,945, p<0.01). The higher cost in HIV-positive patients with at least one comorbidity can be explained by the higher number of hospitalization days (3.4 SD=10.9 vs. 1.0 SD=4.0, p<0.01) and the higher number of prescriptions (151.3 SD=261.6 vs. 76.1 SD=193.8, p<0.01) than in HIV-positive patients with no comorbidities. CONCLUSIONS: The presence of comorbidities has an impact on the burden associated with HIV leading to a significant difference in total health care cost observed between HIV-positive patients with at least one comorbidity and HIV-positive patients with no comorbidities.