Abstract Rationale Persons living with HIV (PLWH) now face a disproportionate burden of age-related comorbidities, including a higher prevalence of chronic respiratory diseases and lower lung function. However, drivers of HIV-associated lung function impairment have not been fully described. In the general population, elevated biomarkers of type 2 (T2) inflammation, particularly high serum eosinophils, have been associated with lung function impairment. PLWH are also known to have high eosinophil counts, however, it remains unclear whether these higher levels are a significant driver of HIV-associated lung function impairment and whether the association with reduced lung function differs by HIV status. Methods We leveraged longitudinal data from the Study of HIV in Etiology of Lung Disease (SHIELD) cohort collected from 2009-2019. SHIELD investigates drivers of lung disease among PLWH and matched HIV-uninfected controls. Participants complete spirometry bi-annually and serum eosinophil counts annually. FEV1 % predicted was the primary outcome in regression models using generalized estimating equations (GEE) accounting for repeated measures. In regression models designed to assess the joint and independent effect of eosinophils and HIV on FEV1, high eosinophils(300 cells/µL) was modeled dichotomously. HIV-uninfected participants with low eosinophils were the reference population. Covariates included age, sex, race, smoking history (status and pack-years) and injection drug use. To limit confounding, participants with asthma were excluded. A separate interaction analysis was performed to assess whether the relationship between eosinophils and FEV1 differed by HIV status. Results We analyzed data from 1,459 participants with a median age of 50 years, who contributed 8378 spirometry measures. The cohort was predominantly black (85%), and 30% were PLWH. PLWH with eosinophil count 300 cells/µL had a 5.38 % lower FEV1 % predicted (95% CI: −7.63 to − 3.13) compared to HIV-negative individuals with ≤300 cells/µL (Figure). Among HIV-negative participants, those with eosinophil counts 300 cells/µL had a 2.24% lower FEV1% predicted (95% CI: −3.18 to − 1.30) compared to HIV-negative individuals with eosinophil counts ≤300 cells/µL. In interaction models, HIV modified the association between eosinophils and FEV1 (Pinter=0.013). Conclusion This study is among the first to examine the association between elevated eosinophil levels and lung function among PLWH. Our findings suggest that high eosinophil counts may be a significant driver of lung function impairment among PLWH, and that HIV may modify the relationship between T2 inflammation and lung function impairment. Future studies are warranted to investigate longitudinal lung function trajectories among PLWH with elevated biomarkers of T2 inflammation. This abstract is funded by: NHLBI R01HL154860, NHLBI K23HL164151
Enoh et al. (Fri,) studied this question.