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Background:  Dideoxynucleoside-related neuropathy affects upwards of 20% of patients taking stavudine or didanosine. A possible mechanism is mitochondrial toxicity due to free oxygen species toxicity. Based on this hypothesis, we tested a potent antioxidant formula designed to lessen the systemic clinical effects of mitochondrial toxicity.

Methods:  Of patients with symptomatic peripheral neuropathy taking either stavudine or didanosine 40 were randomly assigned to receive either high-dose micronutrients or placebo twice daily for 12 weeks in a double-blinded fashion. The micronutrient supplement included 3 potent antioxidants: acetyl L-carnitine, n-acetyl cysteine, and alpha lipoic acid. Data were collected at 4-week intervals and consisted of a neuropathy linear analog scale, quality of life measurements (MOS-HIV), CD4 count, focused neurological exam, HIV RNA, serum lactate, fasting insulin, and fasting lipids. Primary efficacy endpoints consisted of improvement in neuropathy symptoms, ability to continue taking a stavudine or didanosine regimen, change in CD4 count, and change in HIV RNA. The statistical analyses were executed using two sided t-tests with an alpha level of 0.05. No adjustments were made for multiple comparisons. Missing values were imputed using a last-observation-carried-forward method.

Results:  Of 40 randomized patients, 28 completed the protocol to week 12. Subjective neuropathy scores improved in both the micronutrient and placebo groups yet revealed no significant difference. There was also no statistically significant difference in neurological exam results. The percentage increase in absolute CD4 count from baseline for the micronutrient group was 26% vs a 2% increase in the placebo group. This difference was statistically significant (p <0.05).

  CD4 increase from baseline (%)