title: Pretreatment CD4 cell slope and progression to AIDS or death in HIV-infected patients initiating antiretroviral therapy--the CASCADE collaboration: a collaboration of 23 cohort studies.
abstract: BACKGROUND
  CD4 cell count is a strong predictor of the subsequent risk of AIDS or death in HIV-infected patients initiating combination antiretroviral therapy (cART). It is not known whether the rate of CD4 cell decline prior to therapy is related to prognosis and should, therefore, influence the decision on when to initiate cART.
  
  
  RESULTS
  We carried out survival analyses of patients from the 23 cohorts of the CASCADE (Concerted Action on SeroConversion to AIDS and Death in Europe) collaboration with a known date of HIV seroconversion and with at least two CD4 measurements prior to initiating cART. For each patient, a pre-cART CD4 slope was estimated using a linear mixed effects model. Our primary outcome was time from initiating cART to a first new AIDS event or death. We included 2,820 treatment-naïve patients initiating cART with a median (interquartile range) pre-cART CD4 cell decline of 61 (46-81) cells/microl per year; 255 patients subsequently experienced a new AIDS event or death and 125 patients died. In an analysis adjusted for established risk factors, the hazard ratio for AIDS or death was 1.01 (95% confidence interval 0.97-1.04) for each 10 cells/microl per year reduction in pre-cART CD4 cell decline. There was also no association between pre-cART CD4 cell slope and survival. Alternative estimates of CD4 cell slope gave similar results. In 1,731 AIDS-free patients with >350 CD4 cells/microl from the pre-cART era, the rate of CD4 cell decline was also not significantly associated with progression to AIDS or death (hazard ratio 0.99, 95% confidence interval 0.94-1.03, for each 10 cells/microl per year reduction in CD4 cell decline).
  
  
  CONCLUSIONS
  The CD4 cell slope does not improve the prediction of clinical outcome in patients with a CD4 cell count above 350 cells/microl. Knowledge of the current CD4 cell count is sufficient when deciding whether to initiate cART in asymptomatic patients. Please see later in the article for the Editors' Summary.
authors.affiliation: Basel Institute for Clinical Epidemiology and Biostatistics, University Hospital Basel, Basel, Switzerland. mwolbers@oucru.org
authors.forename: Marcel
authors.initials: M
authors.lastname: Wolbers
authors.forename: Abdel
authors.initials: A
authors.lastname: Babiker
authors.forename: Caroline
authors.initials: C
authors.lastname: Sabin
authors.forename: Jim
authors.initials: J
authors.lastname: Young
authors.forename: Maria
authors.initials: M
authors.lastname: Dorrucci
authors.forename: Geneviève
authors.initials: G
authors.lastname: Chêne
authors.forename: Cristina
authors.initials: C
authors.lastname: Mussini
authors.forename: Kholoud
authors.initials: K
authors.lastname: Porter
authors.forename: Heiner C
authors.initials: HC
authors.lastname: Bucher
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D000328:Adult; D044966:Anti-Retroviral Agents / Q000627:therapeutic use*; D018791:CD4 Lymphocyte Count; D015331:Cohort Studies; D018450:Disease Progression; D005260:Female; D015658:HIV Infections / Q000150:complications* / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D008297:Male; D017410:Practice Guidelines as Topic; D013997:Time Factors
chemical_list: D044966:Anti-Retroviral Agents