title: The effect of combined antiretroviral therapy on the overall mortality of HIV-infected individuals.
abstract: OBJECTIVE
  To estimate the effect of combined antiretroviral therapy (cART) on mortality among HIV-infected individuals after appropriate adjustment for time-varying confounding by indication.
  
  
  METHODS
  A collaboration of 12 prospective cohort studies from Europe and the United States (the HIV-CAUSAL Collaboration) that includes 62 760 HIV-infected, therapy-naive individuals followed for an average of 3.3 years. Inverse probability weighting of marginal structural models was used to adjust for measured confounding by indication.
  
  
  RESULTS
  Two thousand and thirty-nine individuals died during the follow-up. The mortality hazard ratio was 0.48 (95% confidence interval 0.41-0.57) for cART initiation versus no initiation. In analyses stratified by CD4 cell count at baseline, the corresponding hazard ratios were 0.29 (0.22-0.37) for less than 100 cells/microl, 0.33 (0.25-0.44) for 100 to less than 200 cells/microl, 0.38 (0.28-0.52) for 200 to less than 350 cells/microl, 0.55 (0.41-0.74) for 350 to less than 500 cells/microl, and 0.77 (0.58-1.01) for 500 cells/microl or more. The estimated hazard ratio varied with years since initiation of cART from 0.57 (0.49-0.67) for less than 1 year since initiation to 0.21 (0.14-0.31) for 5 years or more (P value for trend <0.001).
  
  
  CONCLUSIONS
  We estimated that cART halved the average mortality rate in HIV-infected individuals. The mortality reduction was greater in those with worse prognosis at the start of follow-up.
authors.forename: Maile
authors.initials: M
authors.lastname: Ray
authors.forename: Roger
authors.initials: R
authors.lastname: Logan
authors.forename: Jonathan A C
authors.initials: JA
authors.lastname: Sterne
authors.forename: Sonia
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authors.lastname: Hernández-Díaz
authors.forename: James M
authors.initials: JM
authors.lastname: Robins
authors.forename: Caroline
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authors.lastname: Sabin
authors.forename: Loveleen
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authors.lastname: Bansi
authors.forename: Ard
authors.initials: A
authors.lastname: van Sighem
authors.forename: Frank
authors.initials: F
authors.lastname: de Wolf
authors.forename: Dominique
authors.initials: D
authors.lastname: Costagliola
authors.forename: Emilie
authors.initials: E
authors.lastname: Lanoy
authors.forename: Heiner C
authors.initials: HC
authors.lastname: Bucher
authors.forename: Viktor
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authors.lastname: von Wyl
authors.forename: Anna
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authors.lastname: Esteve
authors.forename: Jordi
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authors.lastname: Casbona
authors.forename: Julia
authors.initials: J
authors.lastname: del Amo
authors.forename: Santiago
authors.initials: S
authors.lastname: Moreno
authors.forename: Amy
authors.initials: A
authors.lastname: Justice
authors.forename: Joseph
authors.initials: J
authors.lastname: Goulet
authors.forename: Sara
authors.initials: S
authors.lastname: Lodi
authors.forename: Andrew
authors.initials: A
authors.lastname: Phillips
authors.forename: Rémonie
authors.initials: R
authors.lastname: Seng
authors.forename: Laurence
authors.initials: L
authors.lastname: Meyer
authors.forename: Santiago
authors.initials: S
authors.lastname: Pérez-Hoyos
authors.forename: Patricia
authors.initials: P
authors.lastname: García de Olalla
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Hernán
mesh_terms: D000328:Adult; D023241:Antiretroviral Therapy, Highly Active / Q000401:mortality*; D018791:CD4 Lymphocyte Count; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination / Q000401:mortality; D005060:Europe / Q000453:epidemiology; D005260:Female; D015658:HIV Infections / Q000188:drug therapy / Q000401:mortality*; D015497:HIV-1; D006801:Humans; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D013997:Time Factors; D014481:United States / Q000453:epidemiology; D019562:Viral Load