This retrospective, cross-sectional study assessed the burden of HIV in Israel’s Maccabi Healthcare Services in 2022. Among 2.6 million individuals assessed (lookback period: > 2 decades), 1973 PWH were identified and age-sex-matched (1:5) to 9,865 randomly selected controls without HIV. We compared sociodemographic, clinical characteristics, and healthcare resource utilization (HRU; Jan–Dec 2022) between people with and without HIV and characterized antiretroviral therapy (ART) treatment patterns among PWH (Jan–Dec 2022). Compared to controls, PWH had a higher lifetime prevalence (since 1988; P < 0.001) of several comorbid conditions, including liver disease, chronic kidney disease, any cancer, and hepatitis B and C infections. Additionally, PWH had a higher rate of anxiety and depression (26.2% vs. 13.5%; P < 0.001). PWH showed higher annual HRU than controls, including ~2-fold higher hospitalizations (≥1 new admissions; P < 0.001) and frequent use of emergency, urgent, primary, specialist, and nursing care (P < 0.05). Among 1907 PWH with ≥1 ART prescription, 78.1% had ≥90% coverage in 2022, although 69.1% experienced ART interruption and 7.2% discontinuation, the latter associated with mental health issues. This study recognizes critical gaps in care that could inform strategies to improve clinical outcomes and resource allocation in health systems for PWH.