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Incidence, Timing, and Determinants of Bacterial Pneumonia Among HIV-Infected Patients: Data From the ICONA Foundation Cohort

Mussini, Cristina MD*; Galli, Laura MD; Lepri, Alessandro C. PhD; De Luca, Andrea MD§; Antinori, Andrea MD; Libertone, Raffaella MD; Angarano, Gioacchino MD; Bonfanti, Paolo MD#; Castagna, Antonella MD; d'Arminio Monforte, Antonella MD**for the ICONA Foundation Study Group

JAIDS Journal of Acquired Immune Deficiency Syndromes: July 1st, 2013 - Volume 63 - Issue 3 - p 339–345
doi: 10.1097/QAI.0b013e318295ab85
Clinical Science

Background: The aim of the study was to evaluate incidence and determinants of bacterial pneumonia (BP) after starting combination antiretroviral therapy (cART) in the Italian Cohort of Antiretroviral-Naive Patients.

Methods: Patients free from BP at cART initiation enrolled between 1996 and 2011 were analyzed. Kaplan–Meier curves were calculated to estimate the time to the first episode of BP; uni- and multivariable Cox proportional hazard models, with time-updated covariates, were applied to identify the risk factors of the first episode of BP.

Results: Four thousand nine hundred forty-two patients were followed for a median of 63.7 months (interquartile range: 23.6, 106.7); 73% were men, median age 36 years (interquartile range: 32, 42), 35% hepatitis C virus antibody positive, 28% smokers, 15% with an AIDS diagnosis (not BP) before cART, 46% with nadir CD4+ T-cell count ≤200 cells per microliter. During 27,569 person years, 137 patients developed 156 BPs, for a crude incidence of 5.66 [95% confidence interval (CI): 4.81 to 6.62] per 1000 person years. The probabilities of first BP at 3, 5, 10, and 14 years from cART initiation were 2.0% ± 0.22%, 2.9% ± 0.28%, 4.3% ± 0.42%, and 5.7% ± 0.75%, respectively. The occurrence of a first BP was associated with low nadir CD4+ [hazard ratios (HR) (per 100 cells/μL higher) = 0.86, 95% CI: 0.79 to 0.94], low current CD4+ [HR (per 100 cells/μL higher) = 0.88, 95% CI: 0.84 to 0.92], high CD8+ [HR (per 100 cells/μL higher) = 1.02, 95% CI: 1.01 to 1.03], low hemoglobin [HR (per g/dL higher) = 0.74, 95% CI: 0.71 to 0.78], and unfavorable virological outcome [HR (HIV-RNA >50 vs <50 copies/mL) = 1.29, 95% CI: 1.04 to 1.60] in addition to older age, male gender, non-Italian nationality, smoking, and longer time to cART initiation.

Conclusions: BP is an infrequent clinical event in the cART era and is associated with traditional risk factors, viroimmunological failure to cART, and low hemoglobin.

*Clinic of Infectious Diseases, University of Modena and Reggio Emilia, Modena, Italy;

Clinic of Infectious Diseases, University of Vita-Salute, San Raffaele Hospital, Milan, Italy;

Department of Infection and Population Health, Division of Population Health, University College London, London, UK;

§Division of Infectious Diseases, University Hospital, Siena, Italy;

Department of Infectious Diseases, National Institute of Infectious Diseases, L. Spallanzani, Rome, Italy;

Clinic of Infectious Diseases, University of Bari, Bari, Italy;

#Department of Infectious Diseases, Azienda Ospedaliera Lecco, Lecco, Italy; and

**Clinic of Infectious and Tropical Diseases, San Paolo Hospital, University of Milan, Milan, Italy.

Correspondence to: Cristina Mussini, MD, Clinic of Infectious Diseases, University of Modena and Reggio Emilia, Via del Pozzo 71, 41124 Modena, Italy (e-mail:

Supported by the Italian Cohort of Antiretroviral-Naive Patients Foundation.

The authors have no conflicts of interest to disclose.

Received November 16, 2012

Accepted March 26, 2013

© 2013 Lippincott Williams & Wilkins, Inc.