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Pneumonia in HIV-infected Persons

Increased Risk with Cigarette Smoking and Treatment Interruption

¹ Veterans Affairs Medical Center and George Washington University, Washington, DC; ² Division of Biostatistics, School of Public Health, University of Minnesota, Minneapolis, Minnesota; ³ Service des Maladies Infectieuses et Tropicales–Hôpital Saint-Antoine, Université Pierre et Marie Curie, and Institut Médecine et d'Epidémiologie Appliquée, Paris, France; ⁴ Copenhagen HIV Programme, University of Copenhagen, Copenhagen, Denmark; ⁵ Hospital Clinic–Institut d'Investigacions Biomèdiques August Pi-Sunyer, University of Barcelona, Barcelona, Spain; ⁶ University Hospitals of Leicester, Leicester, and Medical Research Council, London, United Kingdom; ⁷ Michael E. DeBakey Veterans Affairs Medical Center and Baylor College of Medicine, Houston, Texas; ⁸ University of Chile School of Medicine and Arriaran Foundation, Santiago, Chile; ⁹ Department of HIV and Genitourinary Medicine, Kings College, London, United Kingdom; ¹⁰ University of New South Wales, Sydney, Australia; ¹¹ University of Oklahoma College of Medicine and Veterans Affairs Medical Center, Oklahoma City, Oklahoma

Correspondence and requests for reprints should be addressed to Fred M. Gordin, M.D., Chief, Infectious Diseases (151B), Veterans Affairs Medical Center, 50 Irving Street, NW, Washington, DC 20422. E-mail: fred.gordin{at}med.va.gov.

Rationale: Bacterial pneumonia is a major cause of morbidity for HIV-infected persons and contributes to excess mortality in this population.

Objectives: To evaluate the frequency and risk factors for occurrence of bacterial pneumonia in the present era of potent antiretroviral therapy.

Methods: We evaluated data from a randomized trial of episodic antiretroviral therapy. The study, Strategies for Management of Antiretroviral Therapy, enrolled 5,472 participants at 318 sites in 33 countries. Study patients had more than 350 CD4 cells at baseline. Diagnosis of bacterial pneumonia was confirmed by a blinded clinical-events committee.

Measurements and Main Results: During a mean follow-up of 16 months, 116 participants (2.2%) developed at least one episode of bacterial pneumonia. Patients randomized to receive episodic antiretroviral therapy were significantly more likely to develop pneumonia than patients randomized to receive continuous antiretroviral therapy (hazard ratio, 1.55; 95% confidence interval, 1.07–2.25; P = 0.02). Cigarette smoking was a major risk factor: Current-smokers had more than an 80% higher risk of pneumonia compared with never-smokers (hazard ratio, 1.82; 95% confidence interval, 1.09–3.04; P = 0.02). Participants who were on continuous HIV treatment and were current smokers were three times more likely to develop bacterial pneumonia than nonsmokers. Current smoking status was significant, but a past history of smoking was not.

Conclusions: Bacterial pneumonia is a major source of morbidity, even for persons on potent antiretroviral therapy, including those with high CD4 cells. Efforts to reduce this illness should stress the importance of uninterrupted antiretroviral therapy and attainment and/or maintenance of nonsmoking status.

Clinical trial registered with www.clinicaltrials.gov (NCT 00027352).

Key Words: pneumonia • smoking • HIV • bacterial infections

AT A GLANCE COMMENTARY Scientific Knowledge on the Subject Although bacterial pneumonia is known to be a major cause of morbidity and mortality in HIV-infected persons, no large studies have evaluated this problem in the current era of potent antiretroviral therapy. What This Study Adds to the Field This multinational study demonstrates that bacterial pneumonia remains a substantial problem, even in patients with high CD4+ cell counts on HIV therapy. Cigarette smoking was found to be the single greatest risk factor for the development of pneumonia.