Background
The prevalence of chronic obstructive pulmonary disease (COPD) is higher and more severe among people with HIV (PWH) compared to those without HIV. Chronic inflammation, immune dysfunction, and pulmonary and other infections associated with HIV may contribute to accelerated COPD among PWH, especially given the high prevalence of smoking in PWH.
Methods
We determined associations between a panel of 13 biomarkers and prevalent COPD among PWH in the Centers for AIDS Research Network of Integrated Clinical Systems (CNICS) cohort at eight sites. CNICS data included demographic information, clinical inpatient and outpatient data, and self-reported smoking and substance use behaviors. COPD was defined by a validated algorithm using international classification of disease diagnoses plus >90 days on a COPD inhaler medication. Plasma biomarkers were measured at a single timepoint between 2010-2018 among a subset of virally suppressed PWH; substance use data were collected through November 2023. Biomarkers were log-transformed and scaled by standard deviation. We used relative risk regression to estimate associations between biomarker levels and COPD, adjusted for age, sex, CD4 count, and smoking status (never, ever, missing) with sampling weights to account for the sampling design of the biomarker study.
Results
Among 1425 PWH, average age was 47 (SD: 11), and 17% were female. Nearly half (48%) of PWH were non-Hispanic Black and 39% were non-Hispanic White. There were 242 (17%) cases of COPD, and PWH with COPD were older on average and reported more substance use, including smoking. Higher kynurenine/tryptophan [KT] ratio was associated with a 21% greater likelihood of having COPD (Prevalence Ratio [PR]: 1.21; 95%CI: 1.06-1.37). Additional markers of generalized inflammation were associated with COPD including suPAR (PR: 1.23; 95%CI: 1.06-1.42), ICAM-1 (PR: 1.18; 95%CI: 1.04-1.35), sTNFR1 (PR: 1.14; 95%CI: 1.02-1.29), and IL-6 (PR: 1.15; 95%CI: 1.00-1.33) (Table). These findings were consistent with additional adjustment for cannabis use and illicit drug (methamphetamine, cocaine, opioid) use.
Conclusions
We found a novel association between elevated levels of KT ratio and COPD in PWH. Markers of generalized inflammation were also increased in PWH with COPD. An elevated KT ratio has been linked with infections including active tuberculosis and SARS-CoV-2, suggesting chronic inflammatory and microbial stimuli may contribute to the pathogenesis of COPD in PWH.
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