The Relationship between Cd4 Cell Count Nadirs and the Toxicity Profiles of Antiretroviral Regimens

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 >1mmol/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/mm 3 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/mm 3 , respectively, stopped for toxicity reasons; 11/297 (4%), 5/192 (3%) and 3/358 (1%) 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/mm 3 higher; 95% CI 0.49–0.92; P=0.01). Discussion 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.