CEREBROSPINAL-FLUID HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 RNA LEVELS ARE ELEVATED IN NEUROCOGNITIVELY IMPAIRED INDIVIDUALS WITH ACQUIRED-IMMUNODEFICIENCY-SYNDROME

To determine whether cerebrospinal fluid (CSF) viral burden measuremen ts can assist in the evaluation of human immunodeficiency virus (HIV)- associated neurocognitive disorders, we quantified HIV type 1 (HIV-I) RNA in CSF. Because previous findings suggested that disease stage, ly mphocytic pleocytosis, and HIV-1 RNA levels in plasma may influence CS F viral burden, these variables were examined as potential modifying f actors. HIV-1 RNA levels were quantified by using a reverse transcript ase-polymerase chain reaction assay. Performance on a comprehensive ne uropsychological (NP) battery was noted in 97 prospectively enrolled, HIV-infected subjects. Among subjects with acquired immunodeficiency s yndrome (AIDS) (<200 CD4(+) lymphocytes), NP impairment was associated with significantly higher CSF RNA levels (3.1 vs 1.8 log(10) copies/m l; p = 0.02); most impaired subjects met criteria for HIV-associated d ementia or minor cognitive-motor disorder. In subjects without AIDS, C SF RNA and NP impairment were unrelated. Before AIDS, CSF RNA was stro ngly correlated to plasma RNA and to pleocytosis, but in AIDS, CSF and plasma RNA were independent In conclusion, we found elevated CSF HIV- 1 RNA levels in NP impaired subjects with AIDS. Before AIDS, systemic viral replication, possibly through CD4(+) mononuclear cell traffickin g, map govern virus levels in CSF, whereas in AIDS, CD4 cell depletion may unmask a correlation between increased productive central nervous system HIV infection and clinical neurocognitive disorders.