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From the Tufts Neurology Program and Department of Psychiatry (Dr. Navia), Tufts University School of Medicine, Boston, MA; Beth Beth Israel Deaconess Medical Center (Drs. Navia and Lipton), Boston; the CNS Research Institute (Dr. Lipton), Brigham and Women's Hospital and Harvard Medical School, Boston; Harvard School of Public Health (Drs. Dafni and Yiannoutsos, and L. Zaborski), Boston; Mt. Sinai School of Medicine (Dr. Simpson), New York, NY; Case Western Reserve University (Dr. Tucker), Cleveland, OH; University of California (Dr. Singer), Los Angeles, CA; and Johns Hopkins Medical Institutions (Dr. McArthur), Baltimore, MD.
Address correspondence and reprint requests to Dr. Bradford A. Navia, Research Laboratories in Psychiatry, Box 1007, 750 Washington Street, Boston, MA 02111.
Background: Few effective treatments are available for AIDS dementia complex (ADC) and HIV-associated neuropathy. However, recent in vitro studies indicate that nimodipine, a voltage-dependent calcium channel antagonist, can prevent HIV-related neuronal injury and may provide a novel form of treatment for these disorders.
Methods: To determine the safety and possible efficacy of this agent, 41 patients with mild to severe ADC, including 19 patients with neuropathy, were entered into the AIDS Clinical Trial Group multicenter, phase-I and phase-II study. Nimodipine at 60 mg po, five times daily; 30 mg po, three times daily; or placebo was administered for 16 weeks as adjuvant treatment to antiretroviral therapy.
Results: Neuropsychological performance at baseline, measured by the composite neuropsychological Z score (NPZ-8), correlated significantly with the ADC stage and with CSF levels of neopterin, a marker of immune activation. No significant differences in toxicity were observed among the three arms. Intent-to-treat analysis showed no significant change in the NPZ-8, although improvement was suggested in the high-dose arm. In addition, a trend toward stabilization in peripheral neuropathy was observed in both nimodipine arms compared with placebo.
Conclusions: Nimodipine and other similar nonantiretroviral agents may provide a safe and promising avenue of treatment for neurologic disorders associated with HIV infection. The results of this study indicate that further clinical trials are warranted.
Supported in part by the AIDS Clinical Trials Group of the National Institute of Allergy and Infectious Diseases, Miles Pharmaceuticals, Inc., and the American Foundation for AIDS Research.
Received January 9, 1998. Accepted in final form March 18, 1998.
*See the Appendix on page 226 for a list of participating sites and investigators.
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