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

TitleOxidant stress and peripheral neuropathy during antiretroviral therapy: an AIDS clinical trials group study.
Publication TypeJournal Article
Year of Publication2006
AuthorsHulgan T, Hughes M, Sun X, Smeaton LM, Terry E, Robbins GK, Shafer RW, Clifford DB, McComsey GA, Canter JA, Morrow JD, Haas DW
JournalJ Acquir Immune Defic Syndr
Volume42
Issue4
Pagination450-4
Date Published2006 Aug 1
ISSN1525-4135
KeywordsAdult, Anti-HIV Agents, Case-Control Studies, Female, HIV Infections, Humans, Male, Middle Aged, Oxidative Stress, Peripheral Nervous System Diseases, Randomized Controlled Trials as Topic
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.

DOI10.1097/01.qai.0000226792.16216.1c
Alternate JournalJ. Acquir. Immune Defic. Syndr.
PubMed ID16791116