title: Antiretroviral treatment cohort analysis using time-updated CD4 counts: assessment of bias with different analytic methods.
abstract: BACKGROUND
  Survival analysis using time-updated CD4+ counts during antiretroviral therapy is frequently employed to determine risk of clinical events. The time-point when the CD4+ count is assumed to change potentially biases effect estimates but methods used to estimate this are infrequently reported.
  
  
  METHODS
  This study examined the effect of three different estimation methods: assuming i) a constant CD4+ count from date of measurement until the date of next measurement, ii) a constant CD4+ count from the midpoint of the preceding interval until the midpoint of the subsequent interval and iii) a linear interpolation between consecutive CD4+ measurements to provide additional midpoint measurements. Person-time, tuberculosis rates and hazard ratios by CD4+ stratum were compared using all available CD4+ counts (measurement frequency 1-3 months) and 6 monthly measurements from a clinical cohort. Simulated data were used to compare the extent of bias introduced by these methods.
  
  
  RESULTS
  The midpoint method gave the closest fit to person-time spent with low CD4+ counts and for hazard ratios for outcomes both in the clinical dataset and the simulated data.
  
  
  CONCLUSIONS
  The midpoint method presents a simple option to reduce bias in time-updated CD4+ analysis, particularly at low CD4 cell counts and rapidly increasing counts after ART initiation.
authors: Department of Clinical Research, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, United Kingdom. katharina.kranzer@lshtm.ac.uk
authors: Katharina
authors: K
authors: Kranzer
authors: James J
authors: JJ
authors: Lewis
authors: Richard G
authors: RG
authors: White
authors: Judith R
authors: JR
authors: Glynn
authors: Stephen D
authors: SD
authors: Lawn
authors: Keren
authors: K
authors: Middelkoop
authors: Linda-Gail
authors: LG
authors: Bekker
authors: Robin
authors: R
authors: Wood
mesh_terms: D019380:Anti-HIV Agents / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active; D015982:Bias; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects*; D015331:Cohort Studies; D003198:Computer Simulation; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology* / Q000821:virology; D006801:Humans; D013019:South Africa; D016896:Treatment Outcome; D014376:Tuberculosis / Q000188:drug therapy / Q000821:virology; D019562:Viral Load
chemical_list: D019380:Anti-HIV Agents