Oxidant stress and peripheral neuropathy during antiretroviral therapy: An AIDS clinical trials group study

Todd Hulgan, Michael Hughes, Xin Sun, Laura M. Smeaton, Erin Terry, Gregory K. Robbins, Robert W. Shafer, David B. Clifford, Grace A. McComsey, Jeffery A. Canter, Jason D. Morrow, David W. Haas

Research output: Contribution to journalArticle

12 Scopus citations

Abstract

BACKGROUND: Peripheral neuropathy that complicates HIV nucleoside reverse transcriptase inhibitor (NRTI) therapy is likely caused by mitochondrial injury. Mitochondria play a central role in regulating oxidant stress. We explored the relationships between oxidant stress and NRTI-induced peripheral neuropathy. METHODS: The AIDS Clinical Trials Group (ACTG) studied the cases of 384 antiretroviral-naive individuals randomized to receive didanosine/stavudine or zidovudine/lamivudine, plus efavirenz, nelfinavir, or both. The participants were followed for up to 3 years. Peripheral neuropathy was ascertained by signs and symptoms. We performed a case-control study of ACTG 384 participants. Peripheral neuropathy cases and nonneuropathy control subjects were selected from didanosine/stavudine recipients. Alternate control subjects were selected from zidovudine/lamivudine recipients who developed peripheral neuropathy. Oxidant stress was assessed by quantifying F2-isoprostanes (F2-IsoPs) in cryopreserved plasma. RESULTS: Seventy-five cases, 71 control subjects, and 18 alternate control subjects were identified. The median baseline F2-IsoP values were 53 (interquartile range [IQR], 40-85), 57 (IQR, 41-77), and 53 (IQR, 47-101) pg/mL, respectively, and did not differ between cases and control subjects (P = 0.78) or alternate control subjects (P = 0.60). Changes in F2-IsoPs from baseline to time of peripheral neuropathy did not differ significantly between cases (median, 10 [IQR, -17 to 26] pg/mL) and control subjects (median, 4 [IQR, -11 to 17] pg/mL; P = 0.48) or alternate control subjects (median, 1 [IQR, -48 to 10] pg/mL; P = 0.21). CONCLUSIONS: Peripheral neuropathy that complicates antiretroviral therapy with NRTIs was not associated with increased systemic oxidant stress assessed by plasma F2-IsoPs.

Original languageEnglish
Pages (from-to)450-454
Number of pages5
JournalJournal of Acquired Immune Deficiency Syndromes
Volume42
Issue number4
DOIs
StatePublished - Aug 1 2006

Keywords

  • Drug toxicity
  • HIV
  • Oxidative stress
  • Peripheral neuropathies
  • Reverse transcriptase inhibitors

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