Pharmacological frontiers in the treatment of AIDS dementia

Even in the era of highly active antiretroviral therapy, AIDS dementia rema ins an important and devastating complication of human immunodeficiency vir us (HIV-1) infection. Based on the 1997 AIDS case rate of 56 per 100 000 po pulation in the USA, a reasonable estimated incidence of AIDS dementia is 3 -8 per 100 000, similar to that of multiple sclerosis. The pharmacology of AIDS dementia has been dominated by antiretroviral therapies, the best stud ied of which is azidothymidine. New and specific therapies are needed to tr eat and prevent brain injury in the setting of HIV infection. Rational ther apy has been limited by the absence of large, adequate and well-controlled clinical trials using neuroprotective agents or those with disease-modifyin g potential, as well as by an incomplete understanding of the pathophysiolo gy of AIDS dementia. In this review, a summary of evidence-based hypotheses of HIV-associated brain injury is followed by information on current nonan tiretroviral therapeutic trials and their scientific rationale.