BackgroundThe objective of this investigation was to detect evidence of the synergism in the effects of HIV-1 and drug abuse on brain function that has been hypothesized but rarely shown. The investigation incorporated several noteworthy improvements in the approach. It used urine toxicology tests to exclude participants complicated by recent methadone use and illicit drug use. Also, it defined drug abuse on a scale that considered symptom severity. Most importantly, it examined inter-trial variability in brain activity as a potentially more sensitive indicator of group differences and functional impairment than the across-trial average. Methods173 participants were assigned to groups defined by their HIV-1 serostatus and Drug Abuse Screening Test score (DAST < vs. > = 6). They completed a simple letter discrimination task including rare target and rare nontarget stimuli. Event-related electroencephalographic responses and key press responses were measured on each trial. During a separate assessment, posturographic measures were recorded. ResultsThe inter-trial standard deviation of P300-like activity was superior to the mean amplitude of this activity in differentiating the groups. Unlike the mean, it revealed synergistic statistical effects of HIV and drug abuse. It also correlated significantly with static ataxia. ConclusionsInter-trial variability in P300-like activity is a useful marker for detecting subtle and episodic disruptions in brain function. It demonstrates greater sensitivity than the mean amplitude for detecting differences across groups. Also, as a putative indicator of a disruption in the attentional monitoring of behavior, it predicts subtle impairments in gross motor function.