Acetyl-l-carnitine: a pathogenesis based treatment for HIV-associated antiretroviral toxic neuropathy.
BACKGROUND
Nucleoside analogue reverse transcriptase inhibitors (NRTI) disrupt neuronal mitochondrial DNA synthesis, impairing energy metabolism and resulting in a distal symmetrical polyneuropathy (DSP), an antiretroviral toxic neuropathy (ATN) that causes significant morbidity in HIV disease. Serum acetyl-l-carnitine (ALCAR) levels are decreased in neuropathy associated with NRTI therapy. ALCAR enhances neurotrophic support of sensory neurons and promotes energy metabolism, potentially causing nerve regeneration and symptom relief.


OBJECTIVE
To assess the efficacy of oral ALCAR (1500 mg twice daily) for up to 33 months in an open cohort of 21 HIV-positive patients with established ATN.


METHODS
Skin biopsies were excised from the leg before ALCAR treatment, at 6-12 month intervals thereafter and from HIV-negative non-neuropathic controls. Fibre types in epidermal, dermal and sweat gland innervation were quantified immunohistochemically.


RESULTS
After 6 month's treatment, mean immunostaining area for small sensory fibres increased (epidermis 100%, P = 0.006; dermis 133%, P < 0.05) by more than that for all fibre types (epidermis 16%, P = 0.04; dermis 49%, P < 0.05; sweat glands 60%, P < 0.001) or for sympathetic fibres (sweat glands 41%, P < 0.0003). Compared with controls, epidermal, dermal and sweat gland innervation reached 92%, 80% and 69%, respectively, after 6 month's treatment. Innervation improvements continued (epidermis and dermis) or stabilized (sweat glands) after 24 month's treatment. Neuropathic grade improved in 76% of patients and remained unchanged in 19%. HIV RNA load, CD4 and CD8 cell counts did not alter significantly throughout the study.


CONCLUSIONS
ALCAR treatment improves symptoms, causes peripheral nerve regeneration and is proposed as a pathogenesis-based treatment for DSP.
Hart
Andrew M
AM
Blond McIndoe Centre, Royal Free and University College Medical School, London, UK.
Wilson
Andrew D H
AD
Montovani
Cristina
C
Smith
Colette
C
Johnson
Margaret
M
Terenghi
Giorgio
G
Youle
Mike
M
D000108:Acetylcarnitine / Q000627:therapeutic use*; D000328:Adult; D015331:Cohort Studies; D005260:Female; D015658:HIV Infections / Q000188:drug therapy*; D054303:HIV Reverse Transcriptase / Q000037:antagonists & inhibitors*; D015497:HIV-1; D006801:Humans; D008297:Male; D008875:Middle Aged; D009416:Nerve Regeneration / Q000187:drug effects; D018697:Nootropic Agents / Q000627:therapeutic use*; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced / Q000188:drug therapy*; D018894:Reverse Transcriptase Inhibitors / Q000009:adverse effects*
D018697:Nootropic Agents; D018894:Reverse Transcriptase Inhibitors; D000108:Acetylcarnitine; D054303:HIV Reverse Transcriptase