title: Immunological and infectious risk factors for lung cancer in US veterans with HIV: a longitudinal cohort study.
abstract: HIV infection is independently associated with risk of lung cancer, but few data exist for the relation between longitudinal measurements of immune function and lung-cancer risk in people living with HIV.
  
  
  
  We followed up participants with HIV from the Veterans Aging Cohort Study for a minimum of 3 years between Jan 1, 1998, and Dec 31, 2012, and used cancer registry data to identify incident cases of lung cancer. The index date for each patient was the later of the date HIV care began or Jan 1, 1998. We excluded patients with less than 3 years' follow-up, prevalent diagnoses of lung cancer, or incomplete laboratory data. We used Cox regression models to investigate the relation between different time-updated lagged and cumulative exposures (CD4 cell count, CD8 cell count, CD4/CD8 ratio, HIV RNA, and bacterial pneumonia) and risk of lung cancer. Models were adjusted for age, race or ethnicity, smoking, hepatitis C virus infection, alcohol use disorders, drug use disorders, and history of chronic obstructive pulmonary disease and occupational lung disease.
  
  
  
  We identified 277 cases of incident lung cancer in 21 666 participants with HIV. In separate models for each time-updated 12 month lagged, 24 month simple moving average cumulative exposure, increased risk of lung cancer was associated with low CD4 cell count (p trend=0·001), low CD4/CD8 ratio (p trend=0·0001), high HIV RNA concentration (p=0·004), and more cumulative bacterial pneumonia episodes (12 month lag only; p trend=0·0004). In a mutually adjusted model including these factors, CD4/CD8 ratio and cumulative bacterial pneumonia episodes remained significant (p trends 0·003 and 0·004, respectively).
  
  
  
  In our large HIV cohort in the antiretroviral therapy era, we found evidence that dysfunctional immune activation and chronic inflammation contribute to the development of lung cancer in the setting of HIV infection. These findings could be used to target lung-cancer prevention measures to high-risk groups.
  
  
  
  US National Institutes of Health.
authors.affiliation: Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Electronic address: keith.sigel@mssm.edu.
authors.forename: Keith
authors.initials: K
authors.lastname: Sigel
authors.affiliation: Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
authors.forename: Juan
authors.initials: J
authors.lastname: Wisnivesky
authors.affiliation: Department of Medicine, University of Washington School of Medicine, Seattle, WA, USA.
authors.forename: Kristina
authors.initials: K
authors.lastname: Crothers
authors.affiliation: Department of Medicine, VA Connecticut Healthcare System and Yale Schools of Medicine and Public Health, New Haven, CT, USA.
authors.forename: Kirsha
authors.initials: K
authors.lastname: Gordon
authors.affiliation: Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Infectious Diseases Section, James J Peters VA Medical Center, Bronx, NY, USA.
authors.forename: Sheldon T
authors.initials: ST
authors.lastname: Brown
authors.affiliation: Infectious Diseases Section, Atlanta VA Medical Center and Emory University School of Medicine, Decatur, GA, USA.
authors.forename: David
authors.initials: D
authors.lastname: Rimland
authors.affiliation: Infectious Diseases Section, Michael E DeBakey Veterans Affairs Medical Center and Baylor College of Medicine, Houston, TX, USA.
authors.forename: Maria C
authors.initials: MC
authors.lastname: Rodriguez-Barradas
authors.affiliation: Department of Medicine, George Washington University School of Medicine and Washington DC Veterans Affairs Medical Center, Washington, DC, USA.
authors.forename: Cynthia
authors.initials: C
authors.lastname: Gibert
authors.affiliation: Department of Medicine, VA Greater Los Angeles Healthcare System, Los Angeles, CA, USA; David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA.
authors.forename: Matthew Bidwell
authors.initials: MB
authors.lastname: Goetz
authors.affiliation: Division of Infectious Diseases, VA North Texas Health Care System, Dallas, TX, USA.
authors.forename: Roger
authors.initials: R
authors.lastname: Bedimo
authors.affiliation: Center for Population Health Sciences, Stanford University School of Medicine, Palo Alto, CA, USA.
authors.forename: Lesley S
authors.initials: LS
authors.lastname: Park
authors.affiliation: Department of Chronic Disease Epidemiology, Yale School of Public Health, New Haven, CT, USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Dubrow
mesh_terms: D000328:Adult; D018791:CD4 Lymphocyte Count; D016516:CD4-CD8 Ratio; D015331:Cohort Studies; D005260:Female; D005500:Follow-Up Studies; D015658:HIV Infections / Q000150:complications* / Q000276:immunology* / Q000821:virology; D006526:Hepatitis C / Q000453:epidemiology / Q000821:virology; D006801:Humans; D007249:Inflammation; D008137:Longitudinal Studies; D008175:Lung Neoplasms / Q000453:epidemiology / Q000209:etiology* / Q000276:immunology* / Q000821:virology; D008297:Male; D008875:Middle Aged; D018410:Pneumonia, Bacterial / Q000150:complications / Q000453:epidemiology; D015995:Prevalence; D012367:RNA, Viral / Q000097:blood; D012307:Risk Factors; D012907:Smoking; D014481:United States; D014728:Veterans
chemical_list: D012367:RNA, Viral