title: Cause-Specific Mortality in HIV-Positive Patients Who Survived Ten Years after Starting Antiretroviral Therapy.
abstract: OBJECTIVE
  To estimate mortality rates and prognostic factors in HIV-positive patients who started combination antiretroviral therapy between 1996-1999 and survived for more than ten years.
  
  
  METHODS
  We used data from 18 European and North American HIV cohort studies contributing to the Antiretroviral Therapy Cohort Collaboration. We followed up patients from ten years after start of combination antiretroviral therapy. We estimated overall and cause-specific mortality rate ratios for age, sex, transmission through injection drug use, AIDS, CD4 count and HIV-1 RNA.
  
  
  RESULTS
  During 50,593 person years 656/13,011 (5%) patients died. Older age, male sex, injecting drug use transmission, AIDS, and low CD4 count and detectable viral replication ten years after starting combination antiretroviral therapy were associated with higher subsequent mortality. CD4 count at ART start did not predict mortality in models adjusted for patient characteristics ten years after start of antiretroviral therapy. The most frequent causes of death (among 340 classified) were non-AIDS cancer, AIDS, cardiovascular, and liver-related disease. Older age was strongly associated with cardiovascular mortality, injecting drug use transmission with non-AIDS infection and liver-related mortality, and low CD4 and detectable viral replication ten years after starting antiretroviral therapy with AIDS mortality. Five-year mortality risk was <5% in 60% of all patients, and in 30% of those aged over 60 years.
  
  
  CONCLUSIONS
  Viral replication, lower CD4 count, prior AIDS, and transmission via injecting drug use continue to predict higher all-cause and AIDS-related mortality in patients treated with combination antiretroviral therapy for over a decade. Deaths from AIDS and non-AIDS infection are less frequent than deaths from other non-AIDS causes.
authors.affiliation: School of Social and Community Medicine, University of Bristol, Bristol, United Kingdom.
authors.forename: Adam
authors.identifier: http://orcid.org/0000-0003-3462-2898
authors.initials: A
authors.lastname: Trickey
authors.affiliation: School of Social and Community Medicine, University of Bristol, Bristol, United Kingdom.
authors.forename: Margaret T
authors.initials: MT
authors.lastname: May
authors.affiliation: German Centre for Infection Research, partner site Bonn-Cologne, Cologne, Germany.|Department I for Internal Medicine, University Hospital of Cologne, Cologne, Germany.
authors.forename: Janne
authors.initials: J
authors.lastname: Vehreschild
authors.affiliation: Department of Infectious Diseases, Copenhagen University Hospital, Copenhagen, Denmark.
authors.forename: Niels
authors.initials: N
authors.lastname: Obel
authors.affiliation: Division of Infectious Diseases, University of Calgary, Calgary, Canada.
authors.forename: Michael John
authors.initials: MJ
authors.lastname: Gill
authors.affiliation: Center for AIDS Research, University of Washington, Seattle, WA, United States of America.
authors.forename: Heidi
authors.initials: H
authors.lastname: Crane
authors.affiliation: Department of Internal Medicine, University of Bonn, Bonn, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Boesecke
authors.affiliation: Epidemiology and Population Health Program, British Columbia Centre for Excellence in HIV/AIDS, Vancouver, Canada, and Faculty of Health Sciences, Simon Fraser University, Burnaby, Canada.
authors.forename: Hasina
authors.initials: H
authors.lastname: Samji
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, UMR_S 1136, Institut Pierre Louis d'Epidémiologie et de Santé Publique, F-75013, Paris, France.|INSERM, UMR_S 1136, Institut Pierre Louis d'Epidémiologie et de Santé Publique, F-75013, Paris, France.|Université Paris Descartes et Assistance Publique-Hôpitaux de Paris, Groupe hospitalier Cochin Hôtel-Dieu, Paris, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Grabar
authors.affiliation: Centre Hospitalier Universitaire de Bordeaux, Hôpital Pellegrin, Bordeaux, F-33000, France.
authors.forename: Charles
authors.initials: C
authors.lastname: Cazanave
authors.affiliation: Service of Infectious Diseases, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.
authors.forename: Matthias
authors.initials: M
authors.lastname: Cavassini
authors.affiliation: Research Department of Infection and Population Health, UCL Medical School, London, United Kingdom.
authors.forename: Leah
authors.initials: L
authors.lastname: Shepherd
authors.affiliation: Clinic of Infectious Diseases & Tropical Medicine, San Paolo Hospital, University of Milan, Milan, Italy.
authors.forename: Antonella
authors.initials: A
authors.lastname: d'Arminio Monforte
authors.affiliation: Stichting HIV Monitoring, Amsterdam, the Netherlands.
authors.forename: Colette
authors.initials: C
authors.lastname: Smit
authors.affiliation: Division of Infectious Disease, Department of Medicine, University of Alabama, Birmingham, United States of America.
authors.forename: Michael
authors.initials: M
authors.lastname: Saag
authors.affiliation: Research Department of Infection and Population Health, UCL Medical School, London, United Kingdom.
authors.forename: Fiona
authors.initials: F
authors.lastname: Lampe
authors.affiliation: Red de Investigación en Sida, Centro Nacional de Epidemiología, Instituto de Salud Carlos III, Avda. Monforte de Lemos, 5 28029, Madrid, Spain.
authors.forename: Vicky
authors.initials: V
authors.lastname: Hernando
authors.affiliation: La Fe Hospital, Valencia, Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: Montero
authors.affiliation: Innsbruck Medical University, Innsbruck, Austria.
authors.forename: Robert
authors.initials: R
authors.lastname: Zangerle
authors.affiliation: Yale University School of Medicine, New Haven, CT, United States of America, and VA Connecticut Healthcare System, West Haven, CT, United States of America.
authors.forename: Amy C
authors.initials: AC
authors.lastname: Justice
authors.affiliation: Vanderbilt University School of Medicine, Nashville, TN, United States of America.
authors.forename: Timothy
authors.initials: T
authors.lastname: Sterling
authors.affiliation: Hospital Clínic-IDIBAPS, University of Barcelona, Barcelona, Spain.
authors.forename: Jose
authors.initials: J
authors.lastname: Miro
authors.affiliation: School of Social and Community Medicine, University of Bristol, Bristol, United Kingdom.
authors.forename: Suzanne
authors.initials: S
authors.lastname: Ingle
authors.affiliation: School of Social and Community Medicine, University of Bristol, Bristol, United Kingdom.
authors.forename: Jonathan A C
authors.initials: JA
authors.lastname: Sterne
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D019380:Anti-HIV Agents / Q000494:pharmacology / Q000627:therapeutic use*; D003710:Demography; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000401:mortality*; D015497:HIV-1 / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D016019:Survival Analysis; D055815:Young Adult
chemical_list: D019380:Anti-HIV Agents