title: Discordant responses on starting highly active antiretroviral therapy: suboptimal CD4 increases despite early viral suppression in the UK Collaborative HIV Cohort (UK CHIC) Study.
abstract: OBJECTIVE
  Patients starting highly active antiretroviral therapy (HAART) may have a suboptimal CD4 increase despite rapid virological suppression. The frequency and the significance for patient care of this discordant response are uncertain. This study was designed to determine the incidence of a discordant response at two time-points, soon after 6 months and at 12 months, and to determine the relationship with clinical outcomes.
  
  
  METHODS
  Data obtained in the UK Collaborative HIV Cohort Study were analysed. A total of 2584 treatment-naïve patients starting HAART with HIV viral load (VL) > 1000 HIV-1 RNA copies/mL at baseline and < 50 copies/mL within 6 months were included in the analysis. Patients were classified at either 6-10 (midpoint 8) months or 10-14 (midpoint 12) months as having a discordant (CD4 count increase < 100 cells/microL from baseline) or concordant response (CD4 count increase >or= 100 cells/microL).
  
  
  RESULTS
  Discordant responses occurred in 32.1% of patients at 8 months and in 24.2% at 12 months; 35% of those discordant at 8 months were concordant at 12 months. A discordant response was associated with older age, lower baseline VL, and (at 12 months) higher baseline CD4 cell count. In a multivariate analysis it was associated with an increased risk of death, more strongly at 12 months [incidence rate ratio (IRR) 3.35, 95% confidence interval (CI) 1.73-6.47, P < 0.001] than at 8 months (IRR 2.08, 95% CI 1.19-3.64, P = 0.010), but not with new AIDS events.
  
  
  CONCLUSIONS
  Discordant responders have a worse outcome, but assessment at 12 months may be preferred, given the number of 'slow' responders. Management strategies to improve outcomes for discordant responders need to be investigated.
authors.affiliation: Centre for Sexual Health and HIV Research, Research Department of Infection & Population Health, University College London, The Mortimer Market Centre, Camden Primary Care Trust, London, UK. rgilson@gum.ucl.ac.uk
authors.forename: R J C
authors.initials: RJ
authors.lastname: Gilson
authors.forename: S-L
authors.initials: SL
authors.lastname: Man
authors.forename: A
authors.initials: A
authors.lastname: Copas
authors.forename: A
authors.initials: A
authors.lastname: Rider
authors.forename: S
authors.initials: S
authors.lastname: Forsyth
authors.forename: T
authors.initials: T
authors.lastname: Hill
authors.forename: L
authors.initials: L
authors.lastname: Bansi
authors.forename: K
authors.initials: K
authors.lastname: Porter
authors.forename: B
authors.initials: B
authors.lastname: Gazzard
authors.forename: C
authors.initials: C
authors.lastname: Orkin
authors.forename: D
authors.initials: D
authors.lastname: Pillay
authors.forename: A
authors.initials: A
authors.lastname: Schwenk
authors.forename: M
authors.initials: M
authors.lastname: Johnson
authors.forename: P
authors.initials: P
authors.lastname: Easterbook
authors.forename: J
authors.initials: J
authors.lastname: Walsh
authors.forename: M
authors.initials: M
authors.lastname: Fisher
authors.forename: C
authors.initials: C
authors.lastname: Leen
authors.forename: J
authors.initials: J
authors.lastname: Anderson
authors.forename: C A
authors.initials: CA
authors.lastname: Sabin
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000453:epidemiology; D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D015331:Cohort Studies; D018450:Disease Progression; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology* / Q000401:mortality; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D015994:Incidence; D016015:Logistic Models; D008297:Male; D015999:Multivariate Analysis; D013997:Time Factors; D016896:Treatment Outcome; D006113:United Kingdom; D019562:Viral Load
chemical_list: D019380:Anti-HIV Agents