EFFECT OF COMBINATION THERAPY WITH ZIDOVUDINE AND DIDANOSINE ON NEUROPSYCHOLOGICAL FUNCTIONING IN PATIENTS WITH SYMPTOMATIC HIV DISEASE - ACOMPARISON OF SIMULTANEOUS AND ALTERNATING REGIMENS

Objective: To evaluate the effects of treatment with alternating and s imultaneous regimens of zidovudine and didanosine on neuropsychologica l Function in patients with symptomatic HIV-1 disease, focusing on pat ients with possible HIV-1-associated central nervous system (CNS) comp romise at entry. Design: Randomized non-blinded clinical trial. Settin g: Government medical research center. Patients: Thirty-eight patients with symptomatic HIV-1 disease, of whom 21 had evidence of CNS compro mise at entry. Results: After 12 weeks of therapy, overall significant improvements in memory (P < 0.01) and focused attention (P < 0.001) w ere seen on both regimens. These gains, however, were largely limited to those patients with HIV-1-associated CNS compromise at entry (P < 0 .05). Improvements were also noted in receptive vocabulary, reading, p erceptual discrimination and reasoning, divided attention, motor stren gth, and in mood and affect. Improvements in those latter functions we re generally of limited magnitude and were of comparable size for both compromised and non-compromised patients. There was no overall differ ence between the two drug regimens in the effects on CNS parameters. C onclusions: Therapy-related improvements were noted particularly for p atients with HIV-1-associated CNS compromise. Neuropsychological funct ions that have been implicated in AIDS dementia - memory and attention - showed the greatest gains. In contrast to the previously described superiority of the simultaneous regimen with regard to immunologic and virologic parameters, there was no difference between the regimens wi th regard to CNS measures. This supports the contention that the CNS c onstitutes a relatively independent compartment in terms of HIV diseas e and treatment.