A PHASE I II TRIAL OF NIMODIPINE FOR HIV-RELATED NEUROLOGIC COMPLICATIONS/

Background: Few effective treatments are available for AIDS dementia c omplex (ADC) and HIV-associated neuropathy. However, recent in vitro s tudies indicate that nimodipine, a voltage-dependent calcium channel a ntagonist, can prevent HN-related neuronal injury and may provide a no vel form of treatment for these disorders. Methods: To determine the s afety and possible efficacy of this agent, 41 patients with mild to se vere ADC, including 19 patients with neuropathy, were entered into the AIDS Clinical Trial Group multicenter, phase-I and phase-Il study. Ni modipine at 60 mg po, five times daily; 30 mg po, three times daily; o r placebo was administered for 16 weeks as adjuvant treatment to antir etroviral therapy. Results: Neuropsychological performance at baseline , measured by the composite neuropsychological Z score (NPZ-8), correl ated significantly with the ADC stage and with CSF levels of neopterin , a marker of immune activation. No significant differences in toxicit y 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 pe ripheral 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 neurol ogic disorders associated with HIV infection. The results of this stud y indicate that further clinical trials are warranted.