Viral efficacy maintained and safety parameters improved with a reduced dose of stavudine: A pilot study

Objectives: Stavudine (d4T) is a potent but potentially toxic nucleoside reverse transcriptase inhibitor that is still widely used in developing countries. This study's aim was to determine the efficacy and safety profile of lower-dose d4T. Methods: Multi-centre, open-label, single-arm, pilot, 48-week study in French patients weighing >60 kg with viral load <400 HIV-1 RNAcopies/mL who were receiving d4T 40 mg twice daily and then switched to 30 mg twice daily. The primary endpoint was the proportion with plasma viral load <400 copies/mL at week 24. Secondary endpoints included the proportion with <50 copies/mL at weeks 24 and 48, changes in mitochondrial DNA, CD4 cell count and pharmacokinetics, and clinical and laboratory safety. Results: Fifty-seven patients enrolled. Baseline CD4 count was 584 cells/ μL; viral loads were <400 copies/mL and <50 copies/mL in 100% and 89%, respectively. Prior antiretroviral drug exposure was 6.9 years, d4T exposure was 6.3 years. Fifty-six out of 57 (98%) patients had viral load <400 copies/mL and 51 (89%) had viral load <50 copies/mL at week 24. Median CD4 count increased by 63 cells/μL at week 48 (P = 0.006). At 48 weeks, total cholesterol decreased by 0.24 mmol (P = 0.02), high-density lipoprotein cholesterol by 0.15 mmol (P = 0.0001) and alanine aminotransferase by 5.74 mg/dL (P = 0.01). Paired baseline DNA and week 24 RNA mutations were unchanged. Mitochondrial DNA (copies/ cell) content increased from 672 ± 254 to 682 ± 269. d4T area under the plasma concentration time curve (AUC) decreased by 31% (P = 0.003) and C_max by 44% (P = 0.004). Clinical and laboratory parameters improved or were unchanged. Conclusions: Reduced-dose d4T iseffective with improved safety parameters.