Acetyl-l-carnitine and nucleoside reverse transcriptase inhibitor-associated neuropathy in HIV infection.
OBJECTIVE
Antiretroviral toxic neuropathy (ATN) is associated with dideoxynucleoside reverse transcriptase inhibitor use in patients infected with HIV, possibly as a result of mitochondrial toxicity. Acetyl-l-carnitine (ALC) has been linked to symptomatic improvement in ATN. We present an open-label single-arm pilot study to evaluate changes in intra-epidermal nerve fibre (IENF) density and mitochondrial DNA (mtDNA) copies/cell among subjects treated with 3000 mg ALC daily.


METHODS
Punch skin biopsies were examined at baseline and after 24 weeks of therapy. Participants reported neuropathic symptoms using the Gracely Pain Intensity Score. Neurological examinations were completed.


RESULTS
Twenty-one subjects completed the study. ALC was generally well tolerated. The IENF density did not change in cases completing 24 weeks of ALC therapy, with median (90% confidence interval) IENF changes of -1.70 (-3.50, infinity) (P=0.98) and 2.15 (-0.10, infinity) (P=0.11) for the distal leg and proximal thigh, respectively. Fat mtDNA copies/cell did not change with therapy. Improvements in neuropathic pain (P<0.01), paresthesias (P=0.01), and symptoms of numbness (P<0.01) were noted. Similarly, improvement was noted on the Gracely Pain Intensity Score.


CONCLUSIONS
ALC therapy coincided with improvements in subjective measures of pain in this open-label single-arm study. However, changes were not observed in objective measures of IENF density or mtDNA levels, providing little objective support for use of ALC in this setting.
Valcour
V
V
Hawaii AIDS Clinical Research Program, John A. Burns School of Medicine, University of Hawaii, Honolulu, HI, USA. Vvalcour@hawaii.edu
Yeh
T-M
TM
Bartt
R
R
Clifford
D
D
Gerschenson
M
M
Evans
S R
SR
Cohen
B A
BA
Ebenezer
G J
GJ
Hauer
P
P
Millar
L
L
Gould
M
M
Tran
P
P
Shikuma
C
C
Souza
S
S
McArthur
J C
JC
D017088:AIDS-Related Opportunistic Infections / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D000108:Acetylcarnitine / Q000009:adverse effects*; D016001:Confidence Intervals; D004272:DNA, Mitochondrial / Q000187:drug effects; D005260:Female; D015497:HIV-1; D006801:Humans; D008297:Male; D008875:Middle Aged; D009412:Nerve Fibers / Q000187:drug effects / Q000473:pathology; D010147:Pain Measurement; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D010865:Pilot Projects; D018894:Reverse Transcriptase Inhibitors / Q000009:adverse effects*
D004272:DNA, Mitochondrial; D018894:Reverse Transcriptase Inhibitors; D000108:Acetylcarnitine