Therapeutic effects of nucleoside analogues on psychomotor slowing in HIV infection

Objective: Since psychomotor slowing predicts the development of HIV-l-asso ciated dementia, AIDS and death independently of the immune status, there i s urgent need for a neurological therapeutic rationale. Methods: The therapeutic efficacy of nucleoside analogues with different ab ilities to penetrate into the cerebrospinal fluid was assessed in 410 HIV-1 -seropositive patients using the results of detailed fine motor tests, whic h detect minor motor deficits. Patients were selected who showed pathologic al psychomotor slowing as signs of central nervous system (CNS) dysfunction before therapy onset and who were then treated only with nucleoside analog ues for at least 6 months. Results: Both zidovudine and didanosine improve CNS function to an equal de gree when given as monotherapy. Adding a second nucleoside analogue (didano sine, lamivudine, zalcitabine) to zidovudine does not further improve psych omotor performance. However, adding a second nucleoside after a period of z idovudine monotherapy does result in a second but less remarkable therapeut ic effect. Combinations containing stavudine are as effective as those incl uding zidovudine when given as first antiretroviral treatment. Furthermore, stavudine effectively improves motor performance even after pretreatment w ith zidovudine. (C) 2001 Lippincott Williams & Wilkins.