title: Predictors of bacterial pneumonia in Evaluation of Subcutaneous Interleukin-2 in a Randomized International Trial (ESPRIT).
abstract: OBJECTIVE
  Bacterial pneumonia still contributes to morbidity/mortality in HIV infection despite effective combination antiretroviral therapy (cART). Evaluation of Subcutaneous Interleukin-2 in a Randomized International Trial (ESPRIT), a trial of intermittent recombinant interleukin-2 (rIL-2) with cART vs. cART alone (control arm) in HIV-infected adults with CD4 counts ≥300cells/μL, offered the opportunity to explore associations between bacterial pneumonia and rIL-2, a cytokine that increases the risk of some bacterial infections.
  
  
  METHODS
  Baseline and time-updated factors associated with first-episode pneumonia on study were analysed using multivariate proportional hazards regression models. Information on smoking/pneumococcal vaccination history was not collected.
  
  
  RESULTS
  IL-2 cycling was most intense in years 1-2. Over ≈7 years, 93 IL-2 [rate 0.67/100 person-years (PY)] and 86 control (rate 0.63/100 PY) patients experienced a pneumonia event [hazard ratio (HR) 1.06; 95% confidence interval (CI) 0.79, 1.42; P=0.68]. Median CD4 counts prior to pneumonia were 570cells/μL (IL-2 arm) and 463cells/μL (control arm). Baseline risks for bacterial pneumonia included older age, injecting drug use, detectable HIV viral load (VL) and previous recurrent pneumonia; Asian ethnicity was associated with decreased risk. Higher proximal VL (HR for 1 log(10) higher VL 1.28; 95% CI 1.11, 1.47; P<0.001) was associated with increased risk; higher CD4 count prior to the event (HR per 100 cells/μL higher 0.94; 95% CI 0.89, 1.0; P=0.04) decreased risk. Compared with controls, the hazard for a pneumonia event was higher if rIL-2 was received <180 days previously (HR 1.66; 95% CI 1.07, 2.60; P=0.02) vs.≥180 days previously (HR 0.98; 95% CI 0.70, 1.37; P=0.9). Compared with the control group, pneumonia risk in the IL-2 arm decreased over time, with HRs of 1.41, 1.71, 1.16, 0.62 and 0.84 in years 1, 2, 3-4, 5-6 and 7, respectively.
  
  
  CONCLUSIONS
  Bacterial pneumonia rates in cART-treated adults with moderate immunodeficiency are high. The mechanism of the association between bacterial pneumonia and recent IL-2 receipt and/or detectable HIV viraemia warrants further exploration.
authors.affiliation: National Centre in HIV Epidemiology and Clinical Research, University of New South Wales, Sydney, Australia. spett@nchecr.unsw.edu.au
authors.forename: S L
authors.initials: SL
authors.lastname: Pett
authors.forename: C
authors.initials: C
authors.lastname: Carey
authors.forename: E
authors.initials: E
authors.lastname: Lin
authors.forename: D
authors.initials: D
authors.lastname: Wentworth
authors.forename: J
authors.initials: J
authors.lastname: Lazovski
authors.forename: J M
authors.initials: JM
authors.lastname: Miró
authors.forename: F
authors.initials: F
authors.lastname: Gordin
authors.forename: B
authors.initials: B
authors.lastname: Angus
authors.forename: M
authors.initials: M
authors.lastname: Rodriguez-Barradas
authors.forename: R
authors.initials: R
authors.lastname: Rubio
authors.forename: G
authors.initials: G
authors.lastname: Tambussi
authors.forename: D A
authors.initials: DA
authors.lastname: Cooper
authors.forename: S
authors.initials: S
authors.lastname: Emery
mesh_terms: D017088:AIDS-Related Opportunistic Infections / Q000188:drug therapy* / Q000821:virology; D000276:Adjuvants, Immunologic / Q000627:therapeutic use; D000328:Adult; D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D015497:HIV-1; D006801:Humans; D007376:Interleukin-2 / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D018410:Pneumonia, Bacterial / Q000150:complications* / Q000188:drug therapy* / Q000821:virology; D011237:Predictive Value of Tests; D011994:Recombinant Proteins; D019562:Viral Load
chemical_list: D000276:Adjuvants, Immunologic; D007376:Interleukin-2; D011994:Recombinant Proteins
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