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

J Infect Dis. 2008 Apr 15;197(8):1145-55. doi: 10.1086/529523.

Abstract

Background and 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.

Trial registration: ClinicalTrials.gov NCT00027352.

Publication types

  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • AIDS-Related Opportunistic Infections / epidemiology
  • AIDS-Related Opportunistic Infections / mortality
  • Anti-HIV Agents / administration & dosage*
  • CD4 Lymphocyte Count*
  • Drug Administration Schedule
  • HIV / genetics*
  • HIV / immunology*
  • HIV Infections / drug therapy*
  • HIV Infections / immunology
  • HIV Infections / mortality
  • HIV Infections / virology
  • Humans
  • Proportional Hazards Models
  • RNA, Viral / blood*
  • Treatment Outcome

Substances

  • Anti-HIV Agents
  • RNA, Viral

Associated data

  • ClinicalTrials.gov/NCT00027352