title: When to initiate combined antiretroviral therapy to reduce mortality and AIDS-defining illness in HIV-infected persons in developed countries: an observational study.
abstract: BACKGROUND
  Most clinical guidelines recommend that AIDS-free, HIV-infected persons with CD4 cell counts below 0.350 × 10(9) cells/L initiate combined antiretroviral therapy (cART), but the optimal CD4 cell count at which cART should be initiated remains a matter of debate.
  
  
  OBJECTIVE
  To identify the optimal CD4 cell count at which cART should be initiated.
  
  
  METHODS
  Prospective observational data from the HIV-CAUSAL Collaboration and dynamic marginal structural models were used to compare cART initiation strategies for CD4 thresholds between 0.200 and 0.500 × 10(9) cells/L.
  
  
  METHODS
  HIV clinics in Europe and the Veterans Health Administration system in the United States.
  
  
  METHODS
  20, 971 HIV-infected, therapy-naive persons with baseline CD4 cell counts at or above 0.500 × 10(9) cells/L and no previous AIDS-defining illnesses, of whom 8392 had a CD4 cell count that decreased into the range of 0.200 to 0.499 × 10(9) cells/L and were included in the analysis.
  
  
  METHODS
  Hazard ratios and survival proportions for all-cause mortality and a combined end point of AIDS-defining illness or death.
  
  
  RESULTS
  Compared with initiating cART at the CD4 cell count threshold of 0.500 × 10(9) cells/L, the mortality hazard ratio was 1.01 (95% CI, 0.84 to 1.22) for the 0.350 threshold and 1.20 (CI, 0.97 to 1.48) for the 0.200 threshold. The corresponding hazard ratios were 1.38 (CI, 1.23 to 1.56) and 1.90 (CI, 1.67 to 2.15), respectively, for the combined end point of AIDS-defining illness or death.
  
  
  CONCLUSIONS
  CD4 cell count at cART initiation was not randomized. Residual confounding may exist.
  
  
  CONCLUSIONS
  Initiation of cART at a threshold CD4 count of 0.500 × 10(9) cells/L increases AIDS-free survival. However, mortality did not vary substantially with the use of CD4 thresholds between 0.300 and 0.500 × 10(9) cells/L.
authors.affiliation: Harvard School of Public Health, Boston, MA, USA.
authors.forename: Lauren E
authors.initials: LE
authors.lastname: Cain
authors.forename: Roger
authors.initials: R
authors.lastname: Logan
authors.forename: James M
authors.initials: JM
authors.lastname: Robins
authors.forename: Jonathan A C
authors.initials: JA
authors.lastname: Sterne
authors.forename: Caroline
authors.initials: C
authors.lastname: Sabin
authors.forename: Loveleen
authors.initials: L
authors.lastname: Bansi
authors.forename: Amy
authors.initials: A
authors.lastname: Justice
authors.forename: Joseph
authors.initials: J
authors.lastname: Goulet
authors.forename: Ard
authors.initials: A
authors.lastname: van Sighem
authors.forename: Frank
authors.initials: F
authors.lastname: de Wolf
authors.forename: Heiner C
authors.initials: HC
authors.lastname: Bucher
authors.forename: Viktor
authors.initials: V
authors.lastname: von Wyl
authors.forename: Anna
authors.initials: A
authors.lastname: Esteve
authors.forename: Jordi
authors.initials: J
authors.lastname: Casabona
authors.forename: Julia
authors.initials: J
authors.lastname: del Amo
authors.forename: Santiago
authors.initials: S
authors.lastname: Moreno
authors.forename: Remonie
authors.initials: R
authors.lastname: Seng
authors.forename: Laurence
authors.initials: L
authors.lastname: Meyer
authors.forename: Santiago
authors.initials: S
authors.lastname: Perez-Hoyos
authors.forename: Roberto
authors.initials: R
authors.lastname: Muga
authors.forename: Sara
authors.initials: S
authors.lastname: Lodi
authors.forename: Emilie
authors.initials: E
authors.lastname: Lanoy
authors.forename: Dominique
authors.initials: D
authors.lastname: Costagliola
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Hernan
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000188:drug therapy / Q000276:immunology / Q000401:mortality; D044966:Anti-Retroviral Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D018791:CD4 Lymphocyte Count; D002423:Cause of Death; D019049:Developed Countries; D018450:Disease Progression; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology / Q000401:mortality; D006801:Humans; D019370:Observation; D016016:Proportional Hazards Models; D011446:Prospective Studies
chemical_list: D044966:Anti-Retroviral Agents