Predictors of bacterial pneumonia in Evaluation of Subcutaneous Interleukin-2 in a Randomized International Trial (ESPRIT)

Pett, S. L., Carey, C., Lin, E., Wentworth, D., Lazovski, J., Miro, J. M., Gordin, F., Angus, B., Rodriguez-Barradas, M., Rubio, R., Tambussi, G., Cooper, D. A. and Emery, S. (2011) Predictors of bacterial pneumonia in Evaluation of Subcutaneous Interleukin-2 in a Randomized International Trial (ESPRIT). HIV Medicine, 12 4: 219-227. doi:10.1111/j.1468-1293.2010.00875.x


Author Pett, S. L.
Carey, C.
Lin, E.
Wentworth, D.
Lazovski, J.
Miro, J. M.
Gordin, F.
Angus, B.
Rodriguez-Barradas, M.
Rubio, R.
Tambussi, G.
Cooper, D. A.
Emery, S.
Title Predictors of bacterial pneumonia in Evaluation of Subcutaneous Interleukin-2 in a Randomized International Trial (ESPRIT)
Journal name HIV Medicine   Check publisher's open access policy
ISSN 1464-2662
Publication date 2011-04-01
Year available 2010
Sub-type Article (original research)
DOI 10.1111/j.1468-1293.2010.00875.x
Open Access Status Not yet assessed
Volume 12
Issue 4
Start page 219
End page 227
Total pages 9
Place of publication Chichester, West Sussex, United Kingdom
Publisher Wiley-Blackwell Publishing
Language eng
Formatted abstract
Background and Objectives
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 ≥300 cells/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 570 cells/μL (IL-2 arm) and 463 cells/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 log10 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.
Keyword Bacterial pneumonia
Combination antiretroviral therapy
ESPRIT
RIL-2
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: School of Medicine Publications
 
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