Stavudine-associated toxicity in patients on low-dose versus high-dose Stavudine in an HIV treatment cohort

Abstract

Background Stavudine (d4T) is an antiretroviral drug used in developing countries for the management of HIV due to its efficacy and low cost. Concerns over its toxic side effects has led the WHO to recommend that it be phased out. The study aim was to ascertain whether a low, yet efficacious dose of d4T (20 mg twice daily) would lead to fewer incidences of toxicity. Objectives This study compared incidence of toxicity in patients on low dose d4T (20 mg) versus the higher doses (30 mg /40 mg). Methods A retrospective analysis using STATA 12 was conducted on 1086 patients in a South African HIV treatment cohort. They were stratified into 3 d4T dose groups; 20 mg (n=43); 30 mg (n=707); and 40 mg (n=336). Time to onset of toxicity was assessed using survival analysis. Toxicity incidence rates were estimated using Poisson regression. Cox models were used to determine risk factors. Results Median time to onset of toxicity was 217, 137 and 55 weeks for the d4T 20 mg, d4T 30 mg and d4T 40 mg groups, respectively. Toxicity incidence rates per 100 person-years were 43 (95%CI 25 - 76), 67 (95%CI 54 - 83) and 174 (95%CI 143 - 211), respectively. Patients on d4T 20 mg were less likely to develop toxicity compared to the other doses, hazard ratio 0.36 (95%CI 0.20 - 0.65). Female sex was a risk factor for toxicity, hazard ratio 1.58 (95%CI 1.25 2.00). Other identified risk factors included the presence of renal dysfunction as well as BMI. Conclusion d4T 20 mg twice daily led to fewer incidences of toxicity. Further clinical trials are needed to compare this drug dose to other antiretrovirals.