Acetyl-l-carnitine and nucleoside reverse transcriptase inhibitor-associated neuropathy in HIV infection.

TitleAcetyl-l-carnitine and nucleoside reverse transcriptase inhibitor-associated neuropathy in HIV infection.
Publication TypeJournal Article
Year of Publication2009
AuthorsValcour V, Yeh T-M, Bartt R, Clifford D, Gerschenson M, Evans SR, Cohen BA, Ebenezer GJ, Hauer P, Millar L, Gould M, Tran P, Shikuma C, Souza S, McArthur JC
Corporate AuthorsAIDS Clinical Trials Group(ACTG) 5157 protocol team
JournalHIV Med
Volume10
Issue2
Pagination103-10
Date Published2009 Feb
ISSN1468-1293
KeywordsAcetylcarnitine, AIDS-Related Opportunistic Infections, Confidence Intervals, DNA, Mitochondrial, Female, HIV-1, Humans, Male, Middle Aged, Nerve Fibers, Pain Measurement, Peripheral Nervous System Diseases, Pilot Projects, Reverse Transcriptase Inhibitors
Abstract

OBJECTIVES: 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.

DOI10.1111/j.1468-1293.2008.00658.x
Alternate JournalHIV Med.
PubMed ID19200173
PubMed Central IDPMC2653263
Grant List3U01AI046376-05S4 / AI / NIAID NIH HHS / United States
5 U01 A1069415-02 / / PHS HHS / United States
AI 069471 / AI / NIAID NIH HHS / United States
AI069434 / AI / NIAID NIH HHS / United States
AI069465 / AI / NIAID NIH HHS / United States
AI069471 / AI / NIAID NIH HHS / United States
AI069495 / AI / NIAID NIH HHS / United States
AI069556-02 / AI / NIAID NIH HHS / United States
AI25915-(15-20) / AI / NIAID NIH HHS / United States
AI34853 / AI / NIAID NIH HHS / United States
AI38855 / AI / NIAID NIH HHS / United States
AI38858 / AI / NIAID NIH HHS / United States
AI46370 / AI / NIAID NIH HHS / United States
AI68634 / AI / NIAID NIH HHS / United States
AI68636 / AI / NIAID NIH HHS / United States
MD000173 / MD / NIMHD NIH HHS / United States
MH075673 / MH / NIMH NIH HHS / United States
NS0322228 / NS / NINDS NIH HHS / United States
NS032228-10 / NS / NINDS NIH HHS / United States
NS32228 / NS / NINDS NIH HHS / United States
NS44807 / NS / NINDS NIH HHS / United States
RR025005 / RR / NCRR NIH HHS / United States
U01 AI069495 / AI / NIAID NIH HHS / United States
U01 AI069495-03 / AI / NIAID NIH HHS / United States
U01 NS032228 / NS / NINDS NIH HHS / United States
U01 NS032228-12 / NS / NINDS NIH HHS / United States