title: Predictors of CD4 count change over 8 months of follow up in HIV-1-infected patients with a CD4 count>or=300 cells/microL who were assigned to 7.5 MIU interleukin-2.
abstract: BACKGROUND
  ESPRIT is a randomized trial comparing the clinical impact of interleukin (IL)-2 plus antiretrovirals vs antiretrovirals alone. Identification of factors that influence the relationship between IL-2 and CD4 count recovery will enable better personalization of treatment with IL-2 in HIV-1-positive individuals. The IL-2 induction phase consists of three dosing cycles over 6-8 months (7.5 MIU twice a day, for 5 days every 8 weeks).
  
  
  METHODS
  We included patients initiating IL-2 at the 7.5 MIU dose with an 8-month CD4 count, measured at least 30 days after their last cycle. We identified baseline predictors of CD4 count changes over 8 months using linear regression.
  
  
  RESULTS
  Of 2090 patients assigned IL-2, 1673 (80%) were included in the analysis. The median (interquartile range) baseline CD4 count was 461 (370, 587) cells/microL with a median increase of 233 (90, 411) cells/microL at month 8. After adjustments, significant predictors of CD4 count change included CD4 nadir (29.8 cells/microL greater increase per 100 cells/microL higher; P<0.0001), last CD4 count before baseline (mean 36.0 cells/microL greater increase per 100 cells/microL higher; P<0.0001), time from antiretroviral start to baseline (8.3 cells/microL smaller increase per year longer; P=0.001), age (11.7 cells/microL smaller increase per 5 years older; P=0.005) and race (79.7 cells/microL greater increase for black patients vs white patients; P=0.003). A linear relationship existed between total IL-2 dose in the first cycle and CD4 count change (73.1 cells/microL greater increase per 15 MIU higher; P<0.0001).
  
  
  CONCLUSIONS
  Prior nadir and current CD4 counts, age and IL-2 dose are major determinants of CD4 increases induced by with intermittent administration of IL-2 in HIV-1-positive individuals on antiretrovirals. The clinical function of these induced CD4 cells is under study.
authors.affiliation: Hvidovre University Hospital, DK-2650 Hvidovre, Denmark. z.fox@pcps.ucl.ac.uk
authors.forename: Zoe
authors.initials: Z
authors.lastname: Fox
authors.forename: Francisco
authors.initials: F
authors.lastname: Antunes
authors.forename: Rick
authors.initials: R
authors.lastname: Davey
authors.forename: Brian
authors.initials: B
authors.lastname: Gazzard
authors.forename: Nancy
authors.initials: N
authors.lastname: Klimas
authors.forename: Ann
authors.initials: A
authors.lastname: Labriola
authors.forename: Marcelo
authors.initials: M
authors.lastname: Losso
authors.forename: James D
authors.initials: JD
authors.lastname: Neaton
authors.forename: Andrew N
authors.initials: AN
authors.lastname: Phillips
authors.forename: Kiat
authors.initials: K
authors.lastname: Ruxrungtham
authors.forename: Schlomo
authors.initials: S
authors.lastname: Staszewski
authors.forename: Laurence
authors.initials: L
authors.lastname: Weiss
authors.forename: Jens D
authors.initials: JD
authors.lastname: Lundgren
mesh_terms: D000328:Adult; D018791:CD4 Lymphocyte Count / Q000379:methods*; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology; D017320:HIV Protease Inhibitors / Q000627:therapeutic use; D015497:HIV-1; D006801:Humans; D007376:Interleukin-2 / Q000008:administration & dosage*; D008297:Male; D010349:Patient Compliance; D012367:RNA, Viral / Q000032:analysis; D011994:Recombinant Proteins / Q000008:administration & dosage; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use
chemical_list: D017320:HIV Protease Inhibitors; D007376:Interleukin-2; D012367:RNA, Viral; D011994:Recombinant Proteins; D018894:Reverse Transcriptase Inhibitors