Two types of neuropathy are common in HIV infection. The first type, subacute and chronic demyelinating polyneuropathies is uncommon and occurs relatively early in HIV infection, before susceptibility to major opportunistic infections. A second type, predominantly sensory axonal polyneuropathy, develops as a late complication in up to 30% of people with AIDS. The first is felt to have an autoimmune pathogenesis. Like subacute (Guillain-Barré syndrome) or chronic idiopathic demyelinating polyneuropathy (CIPD), which develops in non-HIVinfected persons, it responds favorably to plasma exchange, IVIG or glucgcorticoids, with the former being the cuffently recommended treatment.
The major morbidity of axonal predominantly-sensory polyneuropathy relates to pain and to the fact that patients may have to stop neurotoxic antiretrovirals (i.e., ddI, ddC, or d4T). In some cases, painful buming or tingling may be so severe that the patient avoids shoes or bedclothes. Treatment is symptomatic; anecdotal experience suggests AZT is usually ineffective. The mainstay is amitiiptyline (Elavil®) or other tricyclics initiated at low doses. For patients with lancinating brief bursts of pain, phenytoin, carbamazepine, and topical capsaicin can also be tried. In a study by Dejard and co-workers in 16 patients with chronic painful diabetic neuropathy, mexiletine (10 mg/kg/d PO) relieved the symptoms but not the signs of neuropathy. Mexiletine is a congener of lidocaine currently used as a treatment for ventiicular arrhythniias. A placebo-controlled trial of mexiletine (10 mg/kg/d) for HIV-related neuropathy is underway at the AIDS Community Research Consortium in Redwood City, CA. Preliminary results indicate 8/10 evaluable patients expefienced 50% pain relief on subjective assessment. Two did not improve. One patient was withdrawn due to disseminated MAC and CMV retinitis. Improvement was most likely to occur during the first 3 weeks of treatment, and symptoms retumed within 1 week of cessation of treatment. Side effects included transient GI upset, nausea and vomiting.
ACTG 242 is a placebo-controlled trial comparing mexiletine and amitriptyline for the treatment ofperpheral neuropathy. As of January, 1996, 117/240 patients have been enrolled. Beginning in May 1996, the ACTG will be conducting a trial of nerve growth factor, which bas the potential to stimulate the regeneration of damaged nerve fibers (ACTG 291).
ddC, d4T, and ddI induce a similar neuropathy in a dose-dependent manner (most common with ddC, least with ddI). Patients on such drugs must be monitored for the onset of pain or numbness in the feet. When these therapies are stopped, the symptoms may progress for a few weeks, but usually then gradually reverge.
Chronic AZT therapy can lead to muscle weakness and wasting, perhaps due to an effect on mitochondrial DNA polymerase. Serum creatine kinase is usually elevated and muscle biopsy may show "ragged red" fibers. Discontinuation of AZT allows gradual recovery.
A multi-center randomized clinical trial (CPCRA 022) is underway to study acupuncture alone and in combination with amitriptyline for the relief of the symptoms of peripheral neuropathy. 260 patients will be enrolled.
REFERENCES:
Gabuzda DH. Neurologic disorders associated with HIV infections. J Am Acad Dermatol 22: 1232-6, 1990.
Kent G et al. The safety and efficacy of mexiletine in HIV-associated painful peripheral neuropathy (PPN). VII Intl Conf AIDS, Florence. Vol 1: 199(M.B. 2068), 1991.
Levy D et al. Topical capsaicin in the treatment of painful diabetic neuropathy. Lancet (letter) 324: 776, 1991.
McGrail M et al. Peptide T studies: Neurophysiologic results. VII Intl Conf AIDS, Florence. Vol 1: 194(M.B. 2049), 1991.
Parry GJ. Peripheral neuropathies associated with human immunodeficiency virus infections. Ann Neurol 23(suppl): 49-53, 1988.
Price R et al. Central and peripheral nervous system complications of HIV-1 infection and AIDS. In: AIDS, Etiology, Diagnosis, Treatment and Prevention, eds. DeVita VT, Hellman S and Rosenberg SA. J.B. Lippincott Company, Philadelphia, 3rd ed. 14:237257, 1992.
Doob PR et al. Role of peptide T in palliation of HIV-1 related painful peripheral neuropathy. VII Intl Conf AIDS, Florence. Vol 2: 225(W.B.2173), 1991.
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