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- Title
Viral efficacy maintained and safety parameters improved with a reduced dose of stavudine: a pilot study.
- Authors
Ait-Mohand, H.; Bonmarchand, M.; Guiguet, M.; Slama, L.; Marguet, F.; Behin, A.; Amellal, B.; Bennai, Y.; Peytavin, G.; Calvez, V.; Pialoux, G.; Murphy, R.; Katlama, C.
- Abstract
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 RNA copies/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 Cmax by 44% ( P=0.004). Clinical and laboratory parameters improved or were unchanged. Conclusions Reduced-dose d4T is effective with improved safety parameters.
- Subjects
NUCLEOSIDES; REVERSE transcriptase; DRUG efficacy; ANTIRETROVIRAL agents; PHARMACOKINETICS
- Publication
HIV Medicine, 2008, Vol 9, Issue 9, p738
- ISSN
1464-2662
- Publication type
Article
- DOI
10.1111/j.1468-1293.2008.00616.x