title: Biomarkers and bacterial pneumonia risk in patients with treated HIV infection: a case-control study.
abstract: BACKGROUND
  Despite advances in HIV treatment, bacterial pneumonia continues to cause considerable morbidity and mortality in patients with HIV infection. Studies of biomarker associations with bacterial pneumonia risk in treated HIV-infected patients do not currently exist.
  
  
  METHODS
  We performed a nested, matched, case-control study among participants randomized to continuous combination antiretroviral therapy (cART) in the Strategies for Management of Antiretroviral Therapy trial. Patients who developed bacterial pneumonia (cases) and patients without bacterial pneumonia (controls) were matched 1∶1 on clinical center, smoking status, age, and baseline cART use. Baseline levels of Club Cell Secretory Protein 16 (CC16), Surfactant Protein D (SP-D), C-reactive protein (hsCRP), interleukin-6 (IL-6), and d-dimer were compared between cases and controls.
  
  
  RESULTS
  Cases (n = 72) and controls (n = 72) were 25.7% female, 51.4% black, 65.3% current smokers, 9.7% diabetic, 36.1% co-infected with Hepatitis B/C, and 75.0% were on cART at baseline. Median (IQR) age was 45 (41, 51) years with CD4+ count of 553 (436, 690) cells/mm(3). Baseline CC16 and SP-D were similar between cases and controls, but hsCRP was significantly higher in cases than controls (2.94 µg/mL in cases vs. 1.93 µg/mL in controls; p = 0.02). IL-6 and d-dimer levels were also higher in cases compared to controls, though differences were not statistically significant (p-value 0.06 and 0.10, respectively).
  
  
  CONCLUSIONS
  In patients with cART-treated HIV infection, higher levels of systemic inflammatory markers were associated with increased bacterial pneumonia risk, while two pulmonary-specific inflammatory biomarkers, CC16 and SP-D, were not associated with bacterial pneumonia risk.
authors: Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, University of Minnesota, Minneapolis, Minnesota, United States of America.
authors: Sonja M
authors: SM
authors: Bjerk
authors: Jason V
authors: JV
authors: Baker
authors: Sean
authors: S
authors: Emery
authors: Jacqueline
authors: J
authors: Neuhaus
authors: Brian
authors: B
authors: Angus
authors: Fred M
authors: FM
authors: Gordin
authors: Sarah L
authors: SL
authors: Pett
authors: Christoph
authors: C
authors: Stephan
authors: Ken M
authors: KM
authors: Kunisaki
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood*; D002097:C-Reactive Protein; D016022:Case-Control Studies; D005260:Female; D005338:Fibrin Fibrinogen Degradation Products; D015658:HIV Infections / Q000097:blood* / Q000150:complications* / Q000188:drug therapy; D006801:Humans; D015850:Interleukin-6 / Q000097:blood; D008168:Lung / Q000821:virology; D008297:Male; D008875:Middle Aged; D018410:Pneumonia, Bacterial / Q000097:blood* / Q000175:diagnosis / Q000209:etiology* / Q000821:virology; D037663:Pulmonary Surfactant-Associated Protein D / Q000097:blood; D012307:Risk Factors; D014598:Uteroglobin / Q000097:blood
chemical_list: D019380:Anti-HIV Agents; D015415:Biomarkers; D005338:Fibrin Fibrinogen Degradation Products; D015850:Interleukin-6; D037663:Pulmonary Surfactant-Associated Protein D; C556389:SCGB1A1 protein, human; C036309:fibrin fragment D; D002097:C-Reactive Protein; D014598:Uteroglobin