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Involvement of the nervous system by human immunodeficiency virus (HIV) continues to be a serious problem. Among individuals with HIV who have a history of illicit drug use, those coinfected with hepatitis C virus HCV) are a fast-growing population. However, few studies have assessed the penetration of HCV into the central nervous system (CNS) and its clinical and neuropathological impacts on HIV-infected individuals. For this purpose, the distribution of HCV was investigated in the brains of patients infected with HIV. The presence of HCV RNA in the CNS as detected by nested polymerase chain reaction was associated with a history of methamphetamine use, considerable antemortem cognitive impairment and abundant astrogliosis, and less-severe HIV encephalitis. HCV antigens were detected by immunoblot analysis, using heparin-purified brain samples, and HCV immunoreactivity was detected in astrocytes and in macrophage-microglial cells. The results support the hypothesis that HCV traffics into the HIV-infected brain, where it might lead to a productive coinfection associated with cognitive impairment. [ABSTRACT FROM AUTHOR]