Acetyl-L-carnitine in HIV-associated antiretroviral toxic neuropathy.
Nucleoside analogue reverse transcriptase inhibitors (NRTIs), used as part of highly active antiretroviral therapy for the treatment of HIV and AIDS, disrupt neuronal mitochondrial DNA synthesis, resulting in antiretroviral toxic neuropathy (ATN). Acetyl-L-carnitine (ALC) enhances neurotrophic support of sensory neurons, potentially causing symptom relief and nerve regeneration, and in addition has numerous other effects on metabolic function that might be of benefit in such patients.ALC has been given to HIV patients with symptomatic ATN in a number of clinical studies administered either twice daily intramuscularly or as oral sachets or tablets. It has been shown to significantly reduce a variety of validated pain ratings, and is generally safe and well tolerated. Using a measure of neuronal innervation in standardised skin biopsies of the affected area, cutaneous nerve density has been improved by the administration of ALC in subjects with symptomatic ATN and reduced epidermal and dermal innervation, associated with clinical improvement, which was maintained over a 4-year period. Improvements were seen in both the structure and function of small sensory fibres, which were sustained over time whilst subjects received ALC. Other open-label, non-randomised studies have shown similar benefits in patients with ATN in terms of pain reduction over the short term. Further placebo-controlled studies of both treatment and prophylaxis have been completed and are under analysis to characterise further the usefulness of this pathogenesis-based therapy for ATN.
Youle
Mike
M
Royal Free Centre for HIV Medicine, Royal Free Hospital, London, UK. mike@mikeyoule.com
D000108:Acetylcarnitine / Q000627:therapeutic use*; D000818:Animals; D023241:Antiretroviral Therapy, Highly Active / Q000009:adverse effects*; D002986:Clinical Trials as Topic; D015658:HIV Infections / Q000150:complications* / Q000188:drug therapy; D006801:Humans; D018697:Nootropic Agents / Q000627:therapeutic use*; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced* / Q000188:drug therapy* / Q000473:pathology
D018697:Nootropic Agents; D000108:Acetylcarnitine
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