ObjectiveThe aim of the study was to investigate symptoms of long-term central nervous system (CNS) toxicity in HIV-positive patients treated with efavirenz (EFV). MethodsWe carried out a single-centre, cross-sectional case-control study comparing patients treated with EFV for at least 6 months with a matched control group. Self-administered, standardized questionnaires including the Depression, Anxiety and Stress Scales (DASS), the Cognitive Failures Questionnaire (CFQ) and a questionnaire on unusual dreams, insomnia, fatigue, dizziness, depersonalization and derealization were administered. ResultsData for 32 matched pairs were analysed. Significantly higher total stress scores (P 5 0.008) were found in the EFV group. Of the patients in this group, 19% also reported severe to extremely severe levels of stress (P 5 0.014), indicating increased difficulty in relaxing, and being more irritable, impatient, agitated and easily upset. Nineteen per cent of patients treated with EFV also reported severe levels of anxiety (P 5 0.059) as assessed with the DASS scale. This patient group also reported a higher rate of unusual dreams (P 5 0.049). No significant differences between groups were found for measures of cognitive impairments, fatigue, dizziness, derealization or depersonalization. ConclusionEFV-treated patients reported higher levels of severe stress and anxiety as well as a higher rate of unusual dreams than patients not treated with EFV. These differences may be an expression of persisting CNS side effects in patients who remain on EFV for a prolonged period.