EFFECTS OF ZIDOVUDINE IN 30 PATIENTS WITH MILD TO END-STAGE AIDS DEMENTIA COMPLEX

Objective: Zidovudine (ZDV) is an inhibitor of HIV replication that ma y have a beneficial effect on patients with AIDS dementia complex (ADC ). However, little is known about the association between long-term ZD V treatment and severity of ADC, ZDV dose or clinical and laboratory r esponse to therapy. Design: An open study on ZDV administration in 30 consecutive patients with ADC. Setting: An infectious diseases hospita l. Patients: Thirty consecutive patients followed-up for 12 months. In terventions: 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. Main outcome measures: Clinical and neurologic al examinations, neuropsychological evaluations, high-field brain magn etic resonance imaging (MRI) and Tc-99m-HM-PAO single photon emission computerized tomography (SPECT). Results: A favourable clinical respon se, defined as reversal to a less severe ADC stage (Price and Brew's c riteria), was observed after 1, 3, 6, 9 and 12 months in 15, 22, 25, 1 9 and 14 patients, respectively. Neither severity of ADC at entry nor ZDV dose correlated with response to treatment. Seven patients died du ring the 12-month follow-up. The only factor associated with longer su rvival 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 respon ded to therapy showed a relapse in initial ADC stage, and two patients a less severe neurological deterioration. Neuropsychological evaluati ons 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. SPEC T scanning revealed a reduction in the extent of uptake defects concom itant with clinical response in nine out of 14 patients. Conclusions: 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.