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Zidovudine (ZDV) is an inhibitor of HIV replication that may have a beneficial effect on patients with AIDS dementia complex (ADC). However, little is known about the association between long-term ZDV treatment and severity of ADC, ZDV dose or clinical and laboratory response to therapy.An open study on ZDV administration in 30 consecutive patients with ADC.An infectious diseases hospital.Thirty consecutive patients followed-up for 12 months.Three oral ZDV doses were used: 1000 mg (nine patients), 750 mg (eight patients) and 500 mg (13 patients) per day, depending on haematological status.Clinical and neurological examinations, neuropsychological evaluations, high-field brain magnetic resonance imaging (MRI) and 99mtTc-HM-PAO single photon emission computerized tomography (SPECT).A favourable clinical response, defined as reversal to a less severe ADC stage (Price and Brew's criteria), was observed after 1, 3, 6, 9 and 12 months in 15, 22, 25, 19 and 14 patients, respectively. Neither severity of ADC at entry nor ZDV dose correlated with response to treatment. Seven patients died during the 12-month follow-up. The only factor associated with longer survival was ADC severity at entry (12-month survival, 0.94 and 0.53, in patients in stages 1 or 2 and in stages 3 or 4, respectively; P< 0.01). After 6–12 months of ZDV treatment six patients who initially responded to therapy showed a relapse in initial ADC stage, and two patients a less severe neurological deterioration. Neuropsychological evaluations showed significant improvement in the Wisconsin Card-Sorting test (P = 0.006 for categories, P = 0.029 for perseverative errors), which is particularly sensitive to cognitive and frontal-lobe type functions. Brain MRI revealed a reduction of the extent of white matter lesions in six out of 13 patients, who also showed clinical improvement. SPECT scanning revealed a reduction in the extent of uptake defects concomitant with clinical response in nine out of 14 patients.ZDV is effective in most patients with mild to end-stage ADC, although the benefit is sometimes only transient; several relapses and deaths occurred after the sixth month of treatment.