Objective:To evaluate the prevalence of HIV-related central nervous system (CNS) lesions (HIV-encephalitis and/or HIV-leukoencephalopathy: HIV-E/L) with and without concomitant opportunistic diseases in a large autopsy series, and to correlate it with the changes in antiretroviral treatment that have occurred since the beginning of the epidemic.Methods:We reviewed 1597 consecutive autopsies of HIV-positive patients performed between 1984 and 2000, and divided into four time periods on the basis of the therapeutic regimens available: 1984–1987, no therapy; 1988–1994, monotherapy (zidovudine); 1995–1996, dual combination therapy with nucleoside reverse transcriptase inhibitors (NRTI); and 1997–2000, triple combination therapy including two NRTI and at least one protease inhibitor or non-NRTI. The data concerning the treatment actually received were collected only for the patients who died during the last period. The χ2-test was used to assess the significance of the differences in prevalence.Results:The CNS of 1210 patients (76%) was affected by opportunistic diseases, HIV-related lesions or both. The prevalence of HIV-related lesions in the four periods was respectively 54%, 32%, 18% and 15%; this reduction was statistically significant (P< 0.000001). During the last period, however, differences in HIV-E/L between treated and untreated patients were not statistically significant, although there were fewer than expected cases among the treated patients (six instead of eight) and more than expected among the untreated patients (10 instead of eight).Conclusions:These neuropathological data from a large autopsy series confirm clinical observations concerning the efficacy of antiretroviral treatment in reducing the frequency of HIV-related CNS lesions in AIDS patients.