ABSTRACT: People living with human immunodeficiency virus (PLHIV) are at high risk of developing non-HIV related comorbidities, particularly at older ages. In a retrospective claims database analysis, we compared PLHIV to a matched, non-HIV cohort to assess the prevalence of comorbidities and healthcare costs in PLHIV and the general non-HIV population in Germany. In total, 2,132 adult patients with HIV were identified in the InGef research database with HIV ICD-10 diagnosis within each year from 2011 to 2014. Of these, 1,969 could be matched to a control cohort of 3,938 individuals (1:2 ratio). Matching criteria included age, gender and socio-economic variables. The prevalence of acute renal disease (0.5% vs. 0.2%, p = 0.045), bone fractures due to osteoporosis (6.4% vs. 2.1%, p<0.001), chronic renal disease (4.3% vs. 2.4%, p<0.001), cardiovascular disease (12.8% vs. 10.4%, p = 0.006), Hepatitis B (5.9% vs. 0.3%, p<0.001) and Hepatitis C infection (8.8% vs. 0.3%, p<0.001) was significantly higher in PLHIV compared to the matched non-HIV cohort. Mean costs excluding costs for antiretroviral therapy (ART) were significantly higher in the HIV cohort (8,049€ vs. 3,658€, p<0.05). On average, PLHIV incurred excess costs of 16,441€ for ART, 2,747€ for pharmaceuticals excluding ART (p<0.05), 1,441€ for outpatient care (p<0.05) and 321€ for inpatient care (p<0.05). Devices and remedies' costs were significantly higher in the control cohort with excess costs of 113€ (p<0.05). Considering mean total costs, excluding ART, excess costs for PLHIV amounted to 8,049€ (p<0.05). This analysis demonstrated an increased comorbidity and economic burden of PLHIV compared to matched controls. Our findings suggest that HIV remains an area of high unmet medical need. To improve patient outcomes, adequate HIV management including regular monitoring, screening for comorbidities and optimal ART selection throughout the life course of PLHIV are of key importance.