Safety and tolerability of the antioxidant OPC-14117 in HIV-associated cognitive impairment

Cognitive impairment is a common and disabling complication of advanced HIV infection. Antiretroviral agents are the only proven therapies currently used for the treatment of HIV dementia, but the response to these agents is frequently unsatisfactory, short-lived, or complicated by intolerable side effects. We hypothesized that OPC-14117, a lipophilic antioxidant that acts to scavenge superoxide anion radicals, might ameliorate the toxic interactions between HIV infected macrophages and neurons. We conducted a double-blind, placebo-controlled, randomized clinical trial to assess the safety and tolerability of OPC-14117 240 mg per day. All 30 patients enrolled (15 per group) had cognitive impairment based on performance on neuropsychological tests. The primary outcome was tolerability of the study drug as measured by the proportion of subjects able to complete the study on their assigned dosage of experimental medication. Overall OPC-14117 was as well tolerated as placebo. Five subjects withdrew because of adverse experiences (two placebo, three OPC-14117). The OPC-14117-treated group had better scores on a clinical global impression scale, compared with the placebo group. There were trends toward improvement in the cognitive test scores; however, these changes were not statistically significant. These results demonstrate that this antioxidant intervention is well tolerated in cognitively impaired patients with advanced HIV infection, and suggest that a larger efficacy trial to assess the impact of OPC-14117 on cognitive performance is warranted.