Oxidant stress and peripheral neuropathy during antiretroviral therapy: an AIDS clinical trials group study.
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.
Hulgan
Todd
T
Vanderbilt University School of Medicine, Nashville, TN 37203, USA. todd.hulgan@vanderbilt.edu
Hughes
Michael
M
Sun
Xin
X
Smeaton
Laura M
LM
Terry
Erin
E
Robbins
Gregory K
GK
Shafer
Robert W
RW
Clifford
David B
DB
McComsey
Grace A
GA
Canter
Jeffery A
JA
Morrow
Jason D
JD
Haas
David W
DW
D000328:Adult; D019380:Anti-HIV Agents / Q000009:adverse effects* / Q000627:therapeutic use; D016022:Case-Control Studies; D005260:Female; D015658:HIV Infections / Q000188:drug therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced*; D016032:Randomized Controlled Trials as Topic
D019380:Anti-HIV Agents