CD8+ T cells and Risk for Bacterial Pneumonia and All-Cause ... : JAIDS Journal of Acquired Immune Deficiency Syndromes (original) (raw)

Epidemiology and Prevention

CD8+ T cells and Risk for Bacterial Pneumonia and All-Cause Mortality Among HIV-Infected Women

Gohil, Shruti K. MD, MPH*; Heo, Moonseong PhD†; Schoenbaum, Ellie E. MD†; Celentano, David ScD‡; Pirofski, Liise-anne MD§,‖

*Department of Medicine, Division of Infectious Diseases and

†Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY

‡Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD

Departments of §Medicine

‖Division of Infectious Diseases, Microbiology and Immunology, Albert Einstein College of Medicine and Montefiore Medical Center, Bronx, NY.

Correspondence to: Liise-anne Pirofski, MD, Division of Infectious Diseases, Department of Microbiology and Immunology, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Belfer Building, Room 610, Bronx, NY 10461 (e-mail: [email protected]).

S.K. Gohil obtained the data, directed and interpreted the analysis, and wrote the manuscript; M. Heo completed the statistical analyses and edited the manuscript; E.E. Schoenbaum was an HERS coinvestigator, who guided the statistical analysis approach and its interpretation, and edited the manuscript; D. Celentano was a coinvestigator of the HERS and edited the manuscript; and L. Pirofski was the principal investigator, who directed and interpreted the analysis, and edited the manuscript.

Supported by the National Institutes of Health (Grants R01AI45459 and R01AI44374 to L.P.) and National Institute of Allergy and Infectious Disease institutional Geographic Medicine and Emerging Infections training grant (5T32 AI070117 to S.K.G.).

Presented at the Infectious Disease Society of America Annual Conference, October 2010, Vancouver, British Columbia, Canada.

The authors have no conflicts of interests to disclose.

Received August 12, 2011

Accepted January 17, 2012

Abstract

Background:

Bacterial pneumonia risk is disproportionately high among those infected with HIV. This risk is present across all CD4+ T-cell levels (TCLs), suggesting that additional factors govern susceptibility. This study examines CD8+ TCLs and risk for HIV-associated bacterial pneumonia and all-cause mortality.

Methods:

Demographic, clinical, and laboratory data were obtained for 885 HIV-infected women enrolled in the HIV Epidemiologic Research Study (HERS). Bacterial pneumonia cases were identified using clinical, microbiological, and radiographic criteria. CD8+ TCLs were assessed at 6-month intervals. Statistical methods included Cox proportional hazards regression modeling and covariate-adjusted survival estimates.

Results:

Relative to a referent CD8+ TCL of 401–800 cells per cubic millimeter, risk for bacterial pneumonia was significantly higher when CD8+ TCLs were <400 (hazard ratio 1.65, P = 0.017, 95% confidence interval 1.10 to 2.49), after adjusting for age, CD4+ TCL, viral load, and antiretroviral use. There was also a significantly higher risk of death when CD8+ TCLs were ≤400 cells per cubic millimeter (hazard ratio 1.45, P = 0.04, 95% confidence interval 1.02 to 2.06). Covariate-adjusted survival estimates revealed shorter time to pneumonia and death in this CD8+ TCL category, and the overall associations of the categorized CD8+ TCL with bacterial pneumonia and all-cause mortality were each statistically significant (P = 0.017 and P < 0.0001, respectively).

Conclusions:

CD8+ TCL ≤400 cells per cubic millimeter was associated with increased risk for pneumonia and all-cause mortality in HIV-infected women in the HERS cohort, suggesting that CD8+ TCL could serve as an adjunctive biomarker of pneumonia risk and mortality in HIV-infected individuals.