Thymic Involution and Function in People With HIV and General Population Controls: A Cross-Sectional Analysis From...

Thymic involution, the age-related replacement of thymic soft tissue by fat, has been linked to immunosenescence and chronic inflammation, processes implicated in aging-associated comorbidities. Untreated HIV infection is associated with thymic atrophy and reduced thymic output. Although thymic function may normalize after initiation of antiretroviral therapy, the long-term consequences of HIV infection on thymic involution in people with HIV (PWH) remain unknown. We investigated whether thymic involution differs between PWH and population controls, and how its association with markers of T-cell differentiation and inflammation in PWH. We conducted a cross-sectional analysis including 654 PWH aged ≥ 40 years from the Copenhagen Comorbidity in HIV Infection study and 637 age- and sex-matched population controls from the Copenhagen General Population Study. Thymic tissue was graded on a 4-point scale based on adipose-to-soft tissue proportion on chest CT scans, with higher grades reflecting more soft tissue (i.e., less involution). Thymic output was assessed by signal joint T-cell receptor excision circle (sjTREC) content in buffy coats. PWH had higher odds of a higher thymus grade compared to population controls (adjusted-OR = 1.75, 95% CI = 1.31-2.33), after adjustment for age, sex, pack-years, BMI, waist-to-hip ratio, physical activity, and alcohol intake. Higher thymus grade was associated with greater sjTREC content, and among PWH with higher proportions of naïve CD4⁺ and CD8⁺ T cells, lower proportions of senescent T cells, and lower IL-6 and hs-CRP levels. Our findings indicate thymic involution may be attenuated in some PWH on long-term treatment, and that the preserved thymic output may help mitigate chronic inflammation.