HIV-1 DNA in brains in AIDS and pre-AIDS: correlation with the stage of disease.

Seventeen asymptomatic individuals positive for human immunodeficiency virus type 1 (HIV-1) and 16 patients with acquired immunodeficiency syndrome (AIDS), all with polymerase chain reaction evidence of HIV-1 DNA, were selected for quantitative analysis to correlate the levels of HIV-1 DNA in brain tissue with the stage of infection. The AIDS patients either were clinically asymptomatic or presented various abnormalities. Neuropathological lesions were assessed by morphological and immunohistochemical methods. To determine the level of HIV-1 DNA, semiquantitative nested polymerase chain reaction was applied using a digoxigenin-labeled primer and chemiluminescence. Serial dilutions of standard HIV DNA were run in parallel with brain DNA samples. Among the 16 AIDS brains studied, 9 showed changes characteristic of HIV encephalitis/leukoencephalopathy while 1 showed focal pontine leukoencephalopathy and 6 showed no obvious neuropathological lesions. Abnormalities in pre-AIDS individuals included meningitis, microgliosis, and astrogliosis. Copy numbers of HIV-1 DNA in the brains of AIDS patients were higher than those in asymptomatic individuals (median, 135 vs 45 copies/150,000 cells). However, there was some degree of overlapping between the two groups, with some AIDS patients showing low figures while 3 asymptomatic individuals had high copy numbers. This suggests that the use of HIV-1 DNA load in the central nervous system as an indicator of progression of the disease should be restricted to large series and not single patients.