TreatmentUpdate77 - Vol. 7, No. 7;- April 1997
Sean Hosein
People with HIV/AIDS can develop peripheral neuropathy (PN) -- damage to the nerves in the hands, arms, feet and legs. Several anti-HIV drugs can cause PN, including ddC, ddI and d4T. PN may also be caused by direct damage to nerves from CMV and HIV. Symptoms of PN include sharp "shooting" pains, tingling, and loss of sense of touch. People not infected with HIV but who have diabetes, malfunctioning thyroid glands, and other whose diet may be deficient in vitamins B6, B12, folic acid and magnesium may also develop PN.
Treatment
The first defense against PN is to stop using drugs that can cause it. If this does not help, doctors may then prescribe antidepressants such as imipramine (Tofranil), amitriptyline (Elavil«), and related drugs in doses ranging between 50 and 150 mg/day. The relatively new antidepressant Paxil« may also provide relief although it appears to be weaker than imipramine. Prozac«, related to Paxil, does not appear to be useful in the treatment of PN. Another drug called Mexitil« (mexiletine), in doses of 10 mg/kg of body weight per day has been effective in diabetics with PN. There are also reports that evening primrose oil is useful (see TreatmentUpdate 64 for details on this last product). Now, Italian researchers suggest that the amino acid carnitine may also be useful for the treatment of PN.
Study Details
To understand the role carnitine can play in PN researchers enrolled 12 HIV-infected subjects (1 female, 11 male) who were using AZT with or without ddC, ddI or d4T. No subject was using protease inhibitors and their average CD4+ count was 84 cells. Researchers monitored 4 other groups of people, comparing them to the first group of 12:
* 11 PHAs without PN who used AZT alone
* 10 PHAs without PN who used ddI alone
* 13 healthy people without PN
* 10 non-HIV-infected subjects with PN
The doses of drugs used were:
* ddC - 2.25 mg/day
* ddI - 500 mg/day
* d4T - 60 or 80 mg/day
* AZT - 600 mg/day
Results
In the group of 12 subjects, PN developed 7-13 weeks after they began using ddC, ddI or d4T. They first reported "aching feet" and later "burning" pain also in the feet but not hands. As well, some muscles and reflexes in the feet became slightly weaker. The study doctors linked the development of PN to the use of the three drugs mentioned previously, ruling out other potential causes of PN by means of lab tests.
Counting carnitine
When researchers compared the levels of the different forms of carnitine in blood samples, they found little difference between the 5 groups. However, when they measured the level of acetyl-carnitine, the researchers found that the 12 subjects with PN had, on average, the lowest level among the 5 groups studied. Moreover, the differences in acetyl-carnitine levels between the group of 12 subjects and the other groups was statistically significant; that is, not likely due to chance alone.
What went wrong?
The researchers think that the cells of the 12 subjects who developed PN were unable to convert carnitine into acetyl-carnitine because of the toxicity of ddC, ddI and d4T.
What's next?
The research team suggests that, based on their research and given that the toxicity of acetyl-carnitine is very low, supplements of acetyl-carnitine for the treatment and prevention of PN are reasonable. The problem is that, until researchers conduct studies, it is not clear what dose PHAs should take.
REFERENCES:
1. Calissi PT and Jaber LA. Peripheral diabetic neuropathy: current concepts in treatment. Annals of Pharmacotherapy 1995;29:769-777.
2. Famularo G, Moretti S, Marcellini S, et al. Acetyl-carnitine deficiency in AIDS patients with neurotoxicity on treatment with antiretroviral nucleoside analogues. AIDS 1997;11:185-190.
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Copyright © 1997 - TreatmentUpdate. Reproduced with permission. Reproduction of this article (other than one copy for personal reference) must be cleared through the Editor, The Canadian AIDS Treatment Information Exchange, 555 Richmond St. West, Suite 505, Box 1104, Toronto, ON, M5V 3B1 • Phone: 416-203-7122 • Toll Free: 1-800-263-1638 • Fax: 416-203-8284 http://www.catie.ca
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