title: Inferior clinical outcome of the CD4+ cell count-guided antiretroviral treatment interruption strategy in the SMART study: role of CD4+ Cell counts and HIV RNA levels during follow-up.
abstract: METHODS
  The SMART study compared 2 strategies for using antiretroviral therapy-drug conservation (DC) and viral suppression (VS)-in 5,472 human immunodeficiency virus (HIV)-infected patients with CD4+ cell counts >350 cells/microL. Rates and predictors of opportunistic disease or death (OD/death) and the relative risk (RR) in DC versus VS groups according to the latest CD4+ cell count and HIV RNA level are reported.
  
  
  RESULTS
  During a mean of 16 months of follow-up, DC patients spent more time with a latest CD4+ cell count <350 cells/microL (for DC vs. VS, 31% vs. 8%) and with a latest HIV RNA level >400 copies/mL (71% vs. 28%) and had a higher rate of OD/death (3.4 vs. 1.3/100 person-years) than VS patients. For periods of follow- up with a CD4+ cell count <350 cells/microL, rates of OD/death were increased but similar in the 2 groups (5.7 vs. 4.6/100 person-years), whereas the rates were higher in DC versus VS patients (2.3 vs. 1.0/100 person-years; RR, 2.3 [95% confidence interval, 1.5-3.4]) for periods with the latest CD4+ cell count >or= 350 cells/microL-an increase explained by the higher HIV RNA levels in the DC group.
  
  
  CONCLUSIONS
  The higher risk of OD/death in DC patients was associated with (1) spending more follow-up time with relative immunodeficiency and (2) living longer with uncontrolled HIV replication even at higher CD4+ cell counts. Ongoing HIV replication at a given CD4+ cell count places patients at an excess risk of OD/death.
authors.affiliation: Copenhagen HIV Programme (CHIP), Faculty of Health Sciences, University of Copenhagen, Panum Institute, 2200 Copenhagen N, Denmark. jdl@cphiv.dk
authors.forename: Jens D
authors.initials: JD
authors.lastname: Lundgren
authors.forename: Abdel
authors.initials: A
authors.lastname: Babiker
authors.forename: Wafaa
authors.initials: W
authors.lastname: El-Sadr
authors.forename: Sean
authors.initials: S
authors.lastname: Emery
authors.forename: Birgit
authors.initials: B
authors.lastname: Grund
authors.forename: James D
authors.initials: JD
authors.lastname: Neaton
authors.forename: Jacquie
authors.initials: J
authors.lastname: Neuhaus
authors.forename: Andrew N
authors.initials: AN
authors.lastname: Phillips
mesh_terms: D017088:AIDS-Related Opportunistic Infections / Q000453:epidemiology / Q000401:mortality; D019380:Anti-HIV Agents / Q000008:administration & dosage*; D018791:CD4 Lymphocyte Count; D004334:Drug Administration Schedule; D006678:HIV / Q000235:genetics* / Q000276:immunology*; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology / Q000401:mortality / Q000821:virology; D006801:Humans; D016016:Proportional Hazards Models; D012367:RNA, Viral / Q000097:blood*; D016896:Treatment Outcome
chemical_list: D019380:Anti-HIV Agents; D012367:RNA, Viral