Painful HIV Neuropathy: Treatment with Alpha-Lipoic Acid

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DESCRIPTION (provided by applicant): HIV infection is associated with painful distal peripheral polyneuropathy in up to 35 to 50% of those without AIDS and in more than 70% of those with advanced disease. Pain is located distally in the extremities, is symmetrical, spontaneous, moderate to severe and associated with varying degrees of weakness and sensory loss. The pain is described as burning, pressure and shock-like with both constant and intermittent features. The condition is progressive but may be halted with disease remission. Disability is often significant, arising from the fluctuating intensity of the pain and the character of the pain itself. Peripheral nerve axons and sensory, neuron cell bodies in the dorsal root ganglia are the principal targets of the process leading to symptoms. Conventional medical treatment consists of anticonvulsants, tricyclic antidepressants, opiates and adjuvant medications, all of which have significant side effects and limited effectiveness. Alpha-lipoic acid is an eight carbon disulfide, naturally occurring in all cells of the body, which serves as a critical cofactor for key mitochondrial enzymatic reactions leading to energy production. In high concentrations it acts as an antioxidant directly, regenerates other anti-oxidants such as glutathione and vitamins C and E, and promotes glutathione synthesis. Clinical studies in using alpha-lipoic acid for painful diabetic neuropathy have shown significant benefit at daily oral doses that are well tolerated: Diabetic neuropathy shares both clinical and some pathological features with painful HIV neuropathy. The present study is designed to evaluate the effects of using daily oral supplements of alpha-lipoic acid plus standard medical care in the treatment of painful HIV-associated neuropathy over a 6 month period in subjects 18 and older. A control group will receive standard medical care plus placebo for six months. Primary endpoints include pain, use of pain medication and peripheral nerve function. Measures of current mood, depression and quality of life along with serum markers of HIV disease activity and mitochondrial function will be obtained at baseline and study termination for correlation with clinical outcomes. Possible benefits of the study to patients with HIV-associated painful neuropathy include reduction in pain and disability, reduced use of medications and enhanced cellular metabolism.