Neuropathology of human immunodeficiency virus infection at different disease stages

The authors studied the brains of 471 adults infected with human immunodeficiency virus type 1 (HIV-1): 123 asymptomatic carriers, 127 in an early stage of acquired immunodeficiency syndrome (AIDS) with pulmonary tuberculosis or bacterial infections, and 221 in fully developed AIDS with opportunistic infections or neoplasms. Lymphocyte infiltration of the leptomeninges and of perivascular spaces occurred at all stages, but the frequency was significantly higher in asymptomatic carriers. Microglial nodules appeared at all stages of disease; they were not an early indicator of HIV encephalitis (HIVE). The incidence of HIVE was unrelated to the stage of AIDS, suggesting that HIVE occurs before opportunistic infections and neoplasms. Drug abuse, such as cocaine and opiates, may enhance HIV replication and increase the incidence of HIVE in the early stage of AIDS. Opportunistic infections or lymphoma involved only the brain in 31.2% of persons with fully developed AIDS. Conversely, opportunistic infections or neoplasms involved only organs other than the brain in 55.7% of persons with fully developed AIDS. In 13.1% of persons with fully developed AIDS, opportunistic infections or neoplasms involved the brain and other organs. Multiple intracranial opportunistic infections and lymphoma coexisted in 4.1% of persons with fully developed AIDS. The authors identified cerebrovascular disease in 10.6% of asymptomatic carriers, 7.1% of early AIDS, and 5.0% of fully developed AIDS. The observed sequence of abnormalities may be useful in understanding the progression of HIV disease in the brain.