When to initiate highly active antiretroviral therapy: A cohort approach

Linda Ahdieh-Grant*, Traci E. Yamashita, John P. Phair, Roger Detels, Steven M. Wolinsky, Joseph B. Margolick, Charles R. Rinaldo, Lisa P. Jacobson

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

34 Scopus citations


The appropriate immunologic stage of human immunodeficiency virus infection at which to initiate highly active antiretroviral therapy (HAART) among asymptomatic persons is a core question. A cohort approach using longitudinal data from the US Multicenter AIDS Cohort Study was used to mimic a clinical trial to assess the risk of acquired immunodeficiency syndrome (AIDS) by timing of therapy. Three treatment groups were defined according to CD4+ count (cells/μl) at HAART initiation between July 1995 and January 2000: <200 (deferral to <200, n = 127), 200-349 (deferral to 200-349, n = 130), and 350-499 (immediate treatment, n = 92). Survival analysis was used to compare time to AIDS between groups from the index visit until July 2000. The index visit for the immediate group was the one prior to HAART initiation. For the deferral groups, the index visit was a randomly selected, pre-HAART, AIDS-free visit after July 1990 at which CD4+ counts were 350-499 cells/μl. This strategy accounted for lead time bias. Compared with immediate treatment, the relative hazards of AIDS were 2.68 (p= 0.003) and 1.05 (p= 0.897) for deferral to <200 cells/μl and 200-349 cells/μl, respectively. These results support recent US public health guidelines for deferring HAART initiation until a count of <350 cells/μl. Furthermore, results suggest a potential threshold for HAART initiation in the neighborhood of 275 cells/μl.

Original languageEnglish (US)
Pages (from-to)738-746
Number of pages9
JournalAmerican journal of epidemiology
Issue number8
StatePublished - Apr 15 2003


  • Cohort studies
  • Epidemiologic methods
  • HIV

ASJC Scopus subject areas

  • Epidemiology


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