Human immunodeficiency virus-1 evolutionary patterns associated with pathogenic processes in the brain.

The interplay between pathology and human immunodeficiency virus (HIV) expansion in brain tissues has not been thoroughly assessed in the highly active antiretroviral therapy (HAART) era. HIV-associated dementia (HAD) is marked by progressive brain infection due to recruitment and migration of macrophages in brain tissues; however, the cellular and viral events occurring prior to HAD development and death are under debate. In this study, 66 brain tissues from 11 autopsies were analyzed to assess HIV-1 DNA concentration in brain tissues. In most patients without HAD, it was impossible to amplify HIV-1 from brain tissues. Amplifiable DNA was obtained from three cases of patients on HAART who died due to primary pathology other than HAD: (1) cardiovascular disease, a disease associated with HAART therapy; (2) bacterial infections, including Mycobacterium avium complex, rapid occurrence of extreme dementia; and (3) acquired immunodeficiency syndrome (AIDS)-related lymphoma with meningeal involvement. HIV-1 DNA was also amplified from multiple tissues of two HAD patients. Analysis of HIV-1 nef, gp120, and gp41 sequences showed reduced viral evolution within brain tissues for the non-HAD cases relative to patients with clinical and histological HAD. The present study is the first to show a potential correlation between HIV-1 evolutionary patterns in the brain and different neuropathologies.