BackgroundPeople living with HIV (PLWH) have increased systemic inflammation, and inflammation has been suggested to contribute to the pathogenesis of emphysema. We investigated whether elevated cytokine concentrations (interleukin (IL)-1β, IL-1 receptor antagonist (IL-1RA), IL-2, IL-4, IL-6, IL-10, IL-17A, tumor necrosis factor-alpha (TNFα), interferon-gamma (IFNγ), soluble CD14 (sCD14) and sCD163 were independently associated with radiographic emphysema in PLWH.MethodsWe included PLWH from the Copenhagen Comorbidity in HIV Infection (COCOMO) Study without hepatitis B and C co-infection and with a plasma sample and a chest computed tomography scan available. Emphysema plus trace emphysema was defined as the percentage of low attenuation area under −950 Houndsfield Unit (%LAA-950) using a cut-off at 5%. Cytokine concentrations were measured by ELISA or Luminex immunoassays. An elevated cytokine concentration was defined as above the 75th percentile.ResultsOf 783 PLWH, 147 (18.8%) had emphysema. PLWH were predominantly male (86.0%) and 743 (94.9%) had undetectable viral replication. PLWH with emphysema had higher concentrations of TNFα (median (IQR): 8.2 (6.4-9.8) versus 7.1 (5.7-8.6) pg/ml, p<0.001), IL-1β (0.21 (0.1-0.4) versus 0.17 (0.1-0.3) pg/ml, p=0.004) and IL-6 (3.6 (2.6-4.9) versus 3.1 (2.0-4.3) pg/ml, p=0.023) than PLWH without. In a logistic regression model adjusted for age, sex, ethnicity, smoking status, BMI and CD4 nadir, elevated TNFα (adjusted odds ratio (aOR): 1.78 [95%CI: 1.14-2.76], p=0.011) and IL-1β (aOR: 1.81 [95%CI: 1.16-2.81], p=0.009) were independently associated with emphysema. The association between IL-1β and emphysema was modified by smoking (p-interaction=0.020) with a more pronounced association in never-smokers (aOR: 4.53 [95%CI: 2.05-9.98], p<0.001).ConclusionTwo markers of systemic inflammation, TNFα and IL-1β, were independently associated with emphysema in PLWH and may contribute to the pathogenesis of emphysema. Importantly, the effect of IL-1β seems to be mediated through pathways that are independent of excessive smoking.Clinical Trial Registrationclinicaltrials.gov, identifier NCT02382822.

Before introducing combination antiretroviral therapy (cART), a higher prevalence of emphysema in people living with HIV (PLWH) than in the background population was reported. This systematic literature review aimed to investigate the prevalence of emphysema in PLWH and to compare the prevalence between PLWH and controls in the current cART era. A systematic literature search was conducted in PubMed, EMBASE, Scopus, and Web of Science (WOS), searching for “human immunodeficiency virus (HIV)” and “emphysema” from January 1, 2000 to March 10, 2021. Eligible studies were published after the introduction of cART, included PLWH, and reported the prevalence of emphysema. A total of 17 studies were included, and nine studies also included controls. The weighted average prevalence of emphysema in PLWH was 23% (95% CI: 16–30). In studies including both PLWH and controls the weighted average prevalence were 22% (95% CI: 10–33) and 9.7% (95% CI: 2.3–17), respectively (p = 0.052). The prevalence of emphysema in never-smoking PLWH and controls was just reported in one study and was 18 and 4%, respectively (p < 0.01). Thirteen of the studies had a moderate risk of bias, mainly due to selection of patients. A tendency to higher prevalence of emphysema was found in PLWH in comparison to controls in the current cART era. However, in the included studies, the definition of emphysema varied largely. Thus, to have a clear overview of the prevalence, further studies with well-designed cohorts of PLWH and controls are warranted.