title: Adjudicated morbidity and mortality outcomes by age among individuals with HIV infection on suppressive antiretroviral therapy.
abstract: BACKGROUND
  Non-AIDS conditions such as cardiovascular disease and non-AIDS defining cancers dominate causes of morbidity and mortality among persons with HIV on suppressive combination antiretroviral therapy. Accurate estimates of disease incidence and of risk factors for these conditions are important in planning preventative efforts.
  
  
  METHODS
  With use of medical records, serious non-AIDS events, AIDS events, and causes of death were adjudicated using pre-specified criteria by an Endpoint Review Committee in two large international trials. Rates of serious non-AIDS which include cardiovascular disease, end-stage renal disease, decompensated liver disease, and non-AIDS cancer, and other serious (grade 4) adverse events were determined, overall and by age, over a median follow-up of 4.3 years for 3,570 participants with CD4+ cell count ≥300 cells/mm³ who were taking antiretroviral therapy and had an HIV RNA level ≤500 copies/mL. Cox models were used to examine the effect of age and other baseline factors on risk of a composite outcome of all-cause mortality, AIDS, or serious non-AIDS.
  
  
  RESULTS
  Five-year Kaplan-Meier estimates of the composite outcome, overall and by age were 8.3% (overall), 3.6% (<40), 8.7% (40-49) and 16.1% (≥50), respectively (p<0.001). In addition to age, smoking and higher levels of interleukin-6 and D-dimer were significant predictors of the composite outcome. The composite outcome was dominated by serious non-AIDS events (overall 65% of 277 participants with a composite event). Most serious non-AIDS events were due to cardiovascular disease and non-AIDS cancers.
  
  
  CONCLUSIONS
  To date, few large studies have carefully collected data on serious non-AIDS outcomes. Thus, reliable estimates of event rates are scarce. Data cited here, from a geographically diverse cohort, will be useful for planning studies of interventions aimed at reducing rates of serious non-AIDS events among people with HIV.
authors.affiliation: Division of Biostatistics, School of Public Health, University of Minnesota, Minneapolis, Minnesota, United States of America.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Miller
authors.affiliation: Division of Infectious Diseases, University of Minnesota, Minneapolis, Minnesota, United States of America; Hennepin County Medical Center, Minneapolis, Minnesota, United States of America.
authors.forename: Jason V
authors.initials: JV
authors.lastname: Baker
authors.affiliation: Division of Infectious Diseases, University of Minnesota, Minneapolis, Minnesota, United States of America.
authors.forename: Alison M
authors.initials: AM
authors.lastname: Bormann
authors.affiliation: Division of Infectious Diseases, University of Colorado Anschutz Medical Campus, Aurora, Colorado, United States of America.
authors.forename: Kristine M
authors.initials: KM
authors.lastname: Erlandson
authors.affiliation: Division of Biostatistics, School of Public Health, University of Minnesota, Minneapolis, Minnesota, United States of America.
authors.forename: Katherine
authors.initials: K
authors.lastname: Huppler Hullsiek
authors.affiliation: Veterans Affairs Connecticut Healthcare System, West Haven, Connecticut, United States of America; School of Medicine and Public Health, Yale University, New Haven, Connecticut, United States of America.
authors.forename: Amy C
authors.initials: AC
authors.lastname: Justice
authors.affiliation: Division of Biostatistics, School of Public Health, University of Minnesota, Minneapolis, Minnesota, United States of America.
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Neuhaus
authors.affiliation: irsiCaixa Foundation, Hospital Universitari Germans Trias i Pujol, Universitat Autónoma de Barcelona, Badalona, Spain; Lluita contra la SIDA Foundation, Badalona, Spain.
authors.forename: Roger
authors.initials: R
authors.lastname: Paredes
authors.affiliation: The Kirby Institute, University of New South Wales, Sydney, Australia.
authors.forename: Kathy
authors.initials: K
authors.lastname: Petoumenos
authors.affiliation: Division of Biostatistics, School of Public Health, University of Minnesota, Minneapolis, Minnesota, United States of America.
authors.forename: Deborah
authors.initials: D
authors.lastname: Wentworth
authors.affiliation: Department of Medicine, Imperial College, London, England.
authors.forename: Alan
authors.initials: A
authors.lastname: Winston
authors.affiliation: Division of Biostatistics, School of Public Health, University of Minnesota, Minneapolis, Minnesota, United States of America.
authors.forename: Julian
authors.initials: J
authors.lastname: Wolfson
authors.affiliation: Division of Biostatistics, School of Public Health, University of Minnesota, Minneapolis, Minnesota, United States of America.
authors.forename: James D
authors.initials: JD
authors.lastname: Neaton
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D023241:Antiretroviral Therapy, Highly Active; D002423:Cause of Death; D005260:Female; D005500:Follow-Up Studies; D015658:HIV Infections / Q000188:drug therapy / Q000453:epidemiology* / Q000401:mortality; D006801:Humans; D008297:Male; D008875:Middle Aged; D009017:Morbidity; D009026:Mortality; D012307:Risk Factors; D016896:Treatment Outcome; D055815:Young Adult
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