title: Incidence and risk factors for invasive pneumococcal disease in HIV-infected and non-HIV-infected individuals before and after the introduction of combination antiretroviral therapy: persistent high risk among HIV-infected injecting drug users.
abstract: BACKGROUND
  Invasive pneumococcal disease (IPD) is an important cause of morbidity among individuals infected with human immunodeficiency virus (HIV). We described incidence and risk factors for IPD in HIV-infected and uninfected individuals.
  
  
  METHODS
  Nationwide population-based cohort study of HIV-infected adults treated at all Danish HIV treatment centers during 1995-2012. Nineteen population-matched controls per HIV-infected individual were retrieved. The risk of IPD was assessed using Poisson regression.
  
  
  RESULTS
  The incidence of IPD was 304.7 cases per 100 000 person-years of follow-up (PYFU) in HIV-infected and 12.8 per 100 000 PYFU in HIV-uninfected individuals. After adjusting for confounders, HIV infection (relative risk [RR], 24.4 [95% confidence interval [CI], 23.7-25.1]), male sex (RR, 1.20 [95% CI, 1.16-1.24]), increasing age (per year) (RR, 1.03 [95% CI, 1.03-1.04]), and calendar period (pre-cART RR, 2.80 [95% CI, 2.70-2.91] compared with late cART) were significantly associated with an increased risk of IPD. Among HIV-infected individuals, male sex (RR, 1.57 [95% CI, 1.49-1.66]), smoking (RR, 1.34 [95% CI, 1.26-1.42]), and injecting drug use (RR, 2.51 [95% CI, 2.26-2.67]) were associated with an increased risk of IPD. Detectable viral loads (RR, 1.88 [95% CI, 1.79-1.98]) and a relative fall in CD4 T-cell counts were also associated with an increased risk (≥500 to 350-500 CD4 T cells/µL: RR, 1.29 [95% CI, 1.21-1.37] and <100 cells/µL: RR, 7.4 [95% CI, 6.87-8.02]). The risk of IPD declined over time, although this was not the case for IDUs where the risk remained unchanged.
  
  
  CONCLUSIONS
  The incidence of IPD in HIV-infected individuals remained significantly higher than the incidence observed in non-HIV-infected subjects, despite the widespread use of cART. IDUs have a persistently high risk of IPD. Injecting drug use, smoking, and the receipt of cART are suitable targets for preventive measures in the future.
authors.affiliation: Department of Infectious Diseases, Rigshospitalet Neisseria and Streptococcus Reference Laboratory, Department of Microbiology and Infection Control, Statens Serum Institut, Copenhagen.
authors.forename: Zitta Barrella
authors.initials: ZB
authors.lastname: Harboe
authors.affiliation: Department of Infectious Diseases and Clinical Research Center, Copenhagen University Hospital, Hvidovre.
authors.forename: Mette Vang
authors.initials: MV
authors.lastname: Larsen
authors.affiliation: Department of Infectious Diseases and Clinical Research Center, Copenhagen University Hospital, Hvidovre.
authors.forename: Steen
authors.initials: S
authors.lastname: Ladelund
authors.affiliation: Department of Infectious Diseases and Clinical Research Center, Copenhagen University Hospital, Hvidovre Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen.
authors.forename: Gitte
authors.initials: G
authors.lastname: Kronborg
authors.affiliation: Neisseria and Streptococcus Reference Laboratory, Department of Microbiology and Infection Control, Statens Serum Institut, Copenhagen.
authors.forename: Helle Bossen
authors.initials: HB
authors.lastname: Konradsen
authors.affiliation: Department of Infectious Diseases, Rigshospitalet.
authors.forename: Jan
authors.initials: J
authors.lastname: Gerstoft
authors.affiliation: Department of Infectious Diseases, Aarhus University Hospital.
authors.forename: Carsten Schade
authors.initials: CS
authors.lastname: Larsen
authors.affiliation: Department of Infectious Diseases, Odense University Hospital.
authors.forename: Court
authors.initials: C
authors.lastname: Pedersen
authors.affiliation: Department of Infectious Diseases, Aalborg University Hospital, Denmark.
authors.forename: Gitte
authors.initials: G
authors.lastname: Pedersen
authors.affiliation: Department of Infectious Diseases, Rigshospitalet Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen.
authors.forename: Niels
authors.initials: N
authors.lastname: Obel
authors.affiliation: Department of Infectious Diseases and Clinical Research Center, Copenhagen University Hospital, Hvidovre Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen.
authors.forename: Thomas
authors.initials: T
authors.lastname: Benfield
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D044966:Anti-Retroviral Agents / Q000627:therapeutic use*; D016470:Bacteremia / Q000453:epidemiology*; D015331:Cohort Studies; D003718:Denmark / Q000453:epidemiology; D005260:Female; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy*; D006801:Humans; D015994:Incidence; D008297:Male; D016920:Meningitis, Bacterial / Q000453:epidemiology*; D008875:Middle Aged; D011008:Pneumococcal Infections / Q000453:epidemiology*; D012307:Risk Factors; D015819:Substance Abuse, Intravenous / Q000150:complications*; D055815:Young Adult
chemical_list: D044966:Anti-Retroviral Agents
keywords: HIV; incidence; injecting drug users; invasive pneumococcal disease; risk factors