We report a patient with rapidly accelerating HIV dementia accompanied by seizures and an unusual movement disorder despite highly potent antiretroviral therapy. This clinical constellation was associated with the non-parenteral use of methamphetamine and cocaine. Fractional enhancement time on post contrast magnetic resonance imaging studies revealed a progressive breakdown of the blood brain barrier particularly in the basal ganglia. The movement disorder but not the dementia responded to a combination of dopamine replacement and anticholinergic therapy. While the movement disorder may have been unmasked by concomitant anticonvulsant therapy, we suggest in this instance, that prior drug abuse synergized with HIV to cause a domino effect on cerebral function. Careful attention and analysis to histories of remote non-injecting drug abuse may help substantiate our hypothesis.