Increasing Multimorbidity Burden After COVID-19 Infection Among People With and Without HIV in the United States: Insights From the National Clinical Cohort Collaborative (N3C).

BACKGROUND: People with HIV (PWH) have a disproportionately high burden of chronic comorbidities. However, how their multimorbidity patterns differ from those of the general population and how COVID-19 infection may affect this burden have not been well characterized. METHODS: We conducted a retrospective cohort study using the National COVID Cohort Collaborative (N3C), including adults aged ≥18 years with a confirmed COVID-19 diagnosis between January 1, 2018 and December 31, 2024. Fourteen chronic comorbidities were identified using N3C concept sets. Exploratory factor analysis was used to identify multimorbidity patterns before and after COVID-19 diagnosis. RESULTS: Among 7 500 765 patients with COVID-19, 52,015 (0.7%) were PWH. The median age was 48 years (IQR, 33-63) and 57.3% were female. PWH consistently had a higher multimorbidity burden than PWoH, and this disparity widened after COVID-19: the proportion with ≥ 3 comorbidities rose from 45.0% to 55.9% among PWH versus 22.2% to 29.7% among PWoH. Four multimorbidity factors were identified in both periods: transplant and multiorgan disease; cardiometabolic disorder; substance use, psychiatric disorder, and liver disease; and obesity. After COVID-19, the leading pattern among PWH shifted toward cardiometabolic disorder. CONCLUSIONS: PWH experience a disproportionately high multimorbidity burden, with disparities further amplified after COVID-19 diagnosis and the leading pattern shifting toward cardiometabolic dominance. These findings highlight the need for integrated, multimorbidity-focused care for PWH.