A phase I/II trial of nimodipine for HIV-related neurologic complications.
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 p.o., five times daily; 30 mg p.o., 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.
Navia
B A
BA
Tufts Neurology Program and Department of Psychiatry, Tufts University School of Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA.
Dafni
U
U
Simpson
D
D
Tucker
T
T
Singer
E
E
McArthur
J C
JC
Yiannoutsos
C
C
Zaborski
L
L
Lipton
S A
SA
D015526:AIDS Dementia Complex / Q000188:drug therapy*; D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage; D002121:Calcium Channel Blockers / Q000008:administration & dosage*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009443:Neuritis / Q000188:drug therapy / Q000821:virology*; D009483:Neuropsychological Tests; D009553:Nimodipine / Q000008:administration & dosage*; D011597:Psychomotor Performance; D015215:Zidovudine / Q000008:administration & dosage
D019380:Anti-HIV Agents; D002121:Calcium Channel Blockers; D015215:Zidovudine; D009553:Nimodipine