title: Major clinical outcomes in antiretroviral therapy (ART)-naive participants and in those not receiving ART at baseline in the SMART study.
abstract: BACKGROUND
  The SMART study randomized 5,472 human immunodeficiency virus (HIV)-infected patients with CD4+ cell counts >350 cells/microL to intermittent antiretroviral therapy (ART; the drug conservation [DC] group) versus continuous ART (the viral suppression [VS] group). In the DC group, participants started ART when the CD4+ cell count was <250 cells/microL. Clinical outcomes in participants not receiving ART at entry inform the early use of ART.
  
  
  METHODS
  Patients who were either ART naive (n=249) or who had not been receiving ART for >or= 6 months (n=228) were analyzed. The following clinical outcomes were assessed: (i) opportunistic disease (OD) or death from any cause (OD/death); (ii) OD (fatal or nonfatal); (iii) serious non-AIDS events (cardiovascular, renal, and hepatic disease plus non-AIDS-defining cancers) and non-OD deaths; and (iv) the composite of outcomes (ii) and (iii).
  
  
  RESULTS
  A total of 477 participants (228 in the DC group and 249 in the VS group) were followed (mean, 18 months). For outcome (iv), 21 and 6 events occurred in the DC (7 in ART-naive participants and 14 in those who had not received ART for >or= 6 months) and VS (2 in ART-naive participants and 4 in those who had not received ART for 6 months) groups, respectively. Hazard ratios for DC vs. VS by outcome category were as follows: outcome (i), 3.47 (95% confidence interval [CI], 1.26-9.56; p=.02); outcome (ii), 3.26 (95% CI, 1.04-10.25; p=.04); outcome (iii), 7.02 (95% CI, 1.57-31.38; p=.01); and outcome (iv), 4.19 (95% CI, 1.69-10.39; p=.002 ).
  
  
  CONCLUSIONS
  Initiation of ART at CD4+ cell counts >350 cells/microL compared with <250 cells/microL may reduce both OD and serious non-AIDS events. These findings require validation in a large, randomized clinical trial.
authors.affiliation: Therapeutic and Vaccine Research Program, National Centre in HIV Epidemiology and Clinical Research, University of New South Wales, 376 Victoria St., Sydney, NSW 2010, Australia. semery@nchecr.unsw.edu.au
authors.forename: Sean
authors.initials: S
authors.lastname: Emery
authors.forename: Jacqueline A
authors.initials: JA
authors.lastname: Neuhaus
authors.forename: Andrew N
authors.initials: AN
authors.lastname: Phillips
authors.forename: Abdel
authors.initials: A
authors.lastname: Babiker
authors.forename: Calvin J
authors.initials: CJ
authors.lastname: Cohen
authors.forename: Jose M
authors.initials: JM
authors.lastname: Gatell
authors.forename: Pierre-Marie
authors.initials: PM
authors.lastname: Girard
authors.forename: Birgit
authors.initials: B
authors.lastname: Grund
authors.forename: Matthew
authors.initials: M
authors.lastname: Law
authors.forename: Marcelo H
authors.initials: MH
authors.lastname: Losso
authors.forename: Adrian
authors.initials: A
authors.lastname: Palfreeman
authors.forename: Robin
authors.initials: R
authors.lastname: Wood
mesh_terms: D017088:AIDS-Related Opportunistic Infections / Q000276:immunology / Q000401:mortality; D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage*; D018791:CD4 Lymphocyte Count; D015331:Cohort Studies; D004334:Drug Administration Schedule; D005260:Female; D006678:HIV / Q000276:immunology*; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology / Q000401:mortality / Q000821:virology; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D016896:Treatment Outcome
chemical_list: D019380:Anti-HIV Agents