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Departments of Neurology (Drs. Berger, Arezzo, and Schaumburg) and Neuroscience (Dr. Arezzo), Albert Einstein College of Medicine, Bronx, NY; the Department of Medicine (Dr. Skowron), Brown University, Providence, RI; the Department of Medicine (Dr. Merigan), Stanford University, Stanford, CA; the Department of Medicine (Drs. Bozzette and Richman), University of California, San Diego, CA and Hoffmann-La Roche, Inc. (Dr. Soo), Nutley, NJ.
We administered the antiviral agent 2',3'-dideoxycytidine (ddC) to HIV-infected patients with either ARC or AIDS as part of the AIDS Clinical Treatment Group protocol 012 and serially evaluated them with neuropathic symptom questionnaires, neurologic examinations, nerve conduction studies, and quantitative sensory testing (QST). All patients treated with high-dose ddC (0.06 and 0.03 mg/kg every 4 hours) developed a painful, predominantly sensory peripheral neuropathy, with a mean onset of 7.7 weeks, which reached severe intensity over several days. Abnormalities of vibration QST thresholds preceded clinical symptoms. Treatment with 0.01 mg/kg every 4 hours produced a similar neuropathy, although of milder severity, later onset (mean, 9.3 weeks), and slower progression. In these patients, the onset of clinical symptoms and QST abnormalities were coincident. Only two of six patients treated with 0.005 mg/kg every 4 hours developed clinical or laboratory evidence of neuropathy; in both cases it was very mild and delayed in onset (26 weeks). All patients treated with high-dose ddC reported progression of symptoms (coasting) for 2 to 3 weeks following discontinuation of therapy. This study documents a painful sensory neuropathy resulting from treatment with ddC. With high-dose treatment, only the rapidity of onset and progression differentiated it from the distal, predominantly sensory neuropathy of AIDS.
Address correspondence and reprint requests to Dr. Alan Berger, EMG Laboratory, Montefiore Medical Center, 111 E. 210th St., Bronx, NY 10467.
Supported in part by a grant from the National Institute of Drug Abuse, Grant #DA07055 and a grant from Hoffmann-La Roche, Inc.
Received January 8, 1992. Accepted for publication in final form July 14, 1992.
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