title: The relationship between CD4 cell count nadirs and the toxicity profiles of antiretroviral regimens.
abstract: BACKGROUND
  It has been suggested that a lower pre-highly active antiretroviral therapy (HAART) CD4 count nadir may lead to a greater risk of experiencing HAART-related toxicity. We investigated the relationship between the pre-HAART CD4 count nadir, HAART and the occurrence of laboratory-defined toxicities.
  
  
  METHODS
  Previously antiretroviral-naive individuals starting HAART at the Royal Free Hospital, London, UK, were included. Drug discontinuation, increases in total cholesterol (by > 1 mmol/l), alanine aspartate transferase/ alanine aminotransferase (AST/ALT) (by >2.5 times the upper limit of normal), bilirubin (by > 2.5 times the upper limit of normal), triglycerides (by > 1 mmol/l) and decreases in haemoglobin (by > 2 g/dl) were assessed.
  
  
  RESULTS
  377/847 (45%) individuals starting HAART stopped at least one antiretroviral within the first 48 weeks. Lower CD4 nadirs were not associated with a greater rate of discontinuing antiretrovirals (adjusted hazard ratio (HR)=1.04 per 100 cells/mm3 higher; 95% confidence intervals (CI) 0.99 - 1.10; P = 0.15). 70/297 (24%), 39/192 (20%) and 73/358 (20%) with a CD4 cell nadir of 0-100, 100-200 and 200+ cells/mm3, respectively, stopped for toxicity reasons; 11/297 (4%), 5/192 (3%) and 3/358 (11%) stopped for reasons of insufficient efficacy; 63/297 (21%), 33/192 (17%) and 80/358 (22%) stopped for other reasons (P = 0.1). Reasons for stopping were similar between CD4 nadir groups. Lower CD4 nadirs were not associated with an increased risk of hypercholesterolaemia, anaemia, hypertriglyceridaemia or increases in AST/ALT but were associated with increased incidence of hyperbilirubinaemia (HR=0.67 per 100 cells/mm3 higher; 95% CI 0.49-0.92; P = 0.01).
  
  
  CONCLUSIONS
  Lower CD4 nadirs were not found to be associated either with discontinuing an antiretroviral or with a higher risk of toxicity, except for an increased risk of experiencing an increase in bilirubin levels.
authors.affiliation: Centre for HIV Medicine, Department of Primary Care and Population Sciences, Royal Free and University College Medical School, Royal Free Hospital, London, UK. c.smith@pcps.ucl.ac.uk
authors.forename: J Smith
authors.initials: JS
authors.lastname: Colette
authors.forename: Caroline A
authors.initials: CA
authors.lastname: Sabin
authors.forename: Fiona C
authors.initials: FC
authors.lastname: Lampe
authors.forename: Sapna
authors.initials: S
authors.lastname: Shah
authors.forename: Mervyn
authors.initials: M
authors.lastname: Tyrer
authors.forename: Mike S
authors.initials: MS
authors.lastname: Youle
authors.forename: Ian
authors.initials: I
authors.lastname: Cropley
authors.forename: Margaret A
authors.initials: MA
authors.lastname: Johnson
authors.forename: Andrew N
authors.initials: AN
authors.lastname: Phillips
mesh_terms: D023241:Antiretroviral Therapy, Highly Active / Q000009:adverse effects*; D018791:CD4 Lymphocyte Count; D005260:Female; D015658:HIV Infections / Q000097:blood* / Q000188:drug therapy*; D006801:Humans; D008297:Male