Progression to neuropsychological impairment in human immunodeficiency virus infection predicted by elevated cerebrospinal fluid levels of human immunodeficiency virus RNA

Background If cerebrospinal fluid (CSF) human immunodeficiency virus (HIV) RNA levels are elevated before the development of neuropsychological (NP) impairment, such an observation would support prospective monitoring of CSF HIV RNA levels as well as therapeutic interventions designed to lower CSF HIV levels. Objective To determine whether increased CSF HIV RNA levels at an earlier time predict subsequent progression to NP impairment in HIV-infected subjects. Methods We examined 139 subjects in a prospective cohort study. Comprehensive NP, neuromedical, and laboratory evaluations were performed at initial and follow-up visits at least 6 months apart. Human immunodeficiency virus RNA levels in plasma and CSF were measured with a commercially available, polymerase chain reaction–based assay. To assess the robustness of our findings, we analyzed changes in NP performance over time in 2 ways. First, we used masked clinical ratings of global NP performance to identify individuals who were initially NP normal, and then determined, in a similarly blinded fashion, which of these subjects subsequently became NP impaired. Second, in a separate analysis, we assessed change in subjects' raw scores on each of a series of NP test measures between baseline and follow-up. Results Among subjects who were not impaired at the initial visit, higher levels of HIV RNA in CSF significantly predicted progression to global NP impairment at the follow-up evaluation. Cerebrospinal fluid HIV RNA levels outperformed other clinical and laboratory measures in predicting progression to NP impairment. Higher CSF HIV RNA levels were associated with worsening performance on tests of attention, learning, and motor function. Conclusion Because elevated CSF HIV RNA levels (≥200 copies/mL) predict subsequent progression to NP impairment, monitoring of CSF viral load and therapy to reduce CSF HIV RNA levels may be clinically warranted, even if impairment is not identified at the time of lumbar puncture.