title: Laboratory adverse events and discontinuation of therapy according to CD4(+) cell count at the start of antiretroviral therapy.
abstract: OBJECTIVE
  Few data describe antiretroviral treatment (ART)-related adverse events when treatment is initiated at CD4(+) cell counts more than 350 cells/μl. We compared rates of laboratory-defined adverse events (LDAEs) according to CD4(+) cell count at ART initiation.
  
  
  METHODS
  Analysis of on-going cohort study.
  
  
  METHODS
  ART-naive persons initiating ART from 2000 to 2010 were included. Chi-square, analysis of variance (ANOVA) and Kruskal-Wallis tests compared characteristics among those starting ART with a CD4(+) cell count of 350 or less, 351-499 and at least 500 cells/μl. Time-updated Poisson regression compared rates of LDAE in the three CD4(+) cell strata. Cox proportional hazard models compared risk of ART discontinuation.
  
  
  RESULTS
  Nine thousand, four hundred and six individuals were included: median age 37 years, 61% white, 80% men, median viral load 4.8 log copies/ml. Four hundred and forty-seven (4.9%) and 1099 (11.7%) started ART with a CD4(+) cell count at least 500 and 351-499 cells/μl, respectively. One thousand, two hundred and eighty-three (13.6%) patients experienced at least one LDAE. The rate of LDAE did not differ between those starting ART with a CD4(+) cell count 351-499 and less than 350 cells/μl [relative rate 0.90, 95% confidence interval (CI) 0.74-1.09)], but an increased risk of ART discontinuation was observed (hazard ratio 1.58, 95% CI 1.10-2.27). Those starting ART at CD4(+) cell count at least 500 cells/μl had an increased rate of LDAE (relative rate 1.44, 95% CI 1.13-1.82) but were not more likely to discontinue ART (hazard ratio 1.15, 95% CI 0.64-2.09).
  
  
  CONCLUSIONS
  This study demonstrates the need to consider ART-related toxicities when initiating therapy at CD4(+) cell counts at least 500 cells/μl. Whilst evidence from randomized controlled trials is awaited, the timing of ART initiation in terms of benefits and risks of ART remains an important question.
authors.affiliation: aResearch Department of Infection and Population Health, UCL bImperial College London Department of Medicine, London cThe Lothian University Hospitals NHS Trust, Edinburgh dSt George's Healthcare NHS Trust, London eBrighton and Sussex University Hospitals NHS Trust, Brighton fKings College Hospital NHS Foundation Trust and King's College London gChelsea and Westminster NHS Foundation Trust, London hNorth Bristol NHS Trust, Bristol iRoyal Free Hampstead NHS Trust, London jSouth Tees Hospital NHS Foundation Trust, Middlesbrough kMortimer Market Centre, University College Medical School, London, UK.
authors.forename: Sophie
authors.initials: S
authors.lastname: Jose
authors.forename: Killian
authors.initials: K
authors.lastname: Quinn
authors.forename: Teresa
authors.initials: T
authors.lastname: Hill
authors.forename: Clifford
authors.initials: C
authors.lastname: Leen
authors.forename: John
authors.initials: J
authors.lastname: Walsh
authors.forename: Phillip
authors.initials: P
authors.lastname: Hay
authors.forename: Martin
authors.initials: M
authors.lastname: Fisher
authors.forename: Frank
authors.initials: F
authors.lastname: Post
authors.forename: Mark
authors.initials: M
authors.lastname: Nelson
authors.forename: Mark
authors.initials: M
authors.lastname: Gompels
authors.forename: Margaret
authors.initials: M
authors.lastname: Johnson
authors.forename: David
authors.initials: D
authors.lastname: Chadwick
authors.forename: Richard
authors.initials: R
authors.lastname: Gilson
authors.forename: Caroline
authors.initials: C
authors.lastname: Sabin
authors.forename: Sarah
authors.initials: S
authors.lastname: Fidler
mesh_terms: D000328:Adult; D044966:Anti-Retroviral Agents / Q000009:adverse effects* / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active / Q000009:adverse effects*; D018791:CD4 Lymphocyte Count; D019411:Clinical Laboratory Techniques; D015331:Cohort Studies; D064420:Drug-Related Side Effects and Adverse Reactions / Q000175:diagnosis*; D005260:Female; D015658:HIV Infections / Q000188:drug therapy*; D006801:Humans; D008297:Male; D028761:Withholding Treatment
chemical_list: D044966:Anti-Retroviral Agents