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Progression to Neuropsychological Impairment in Human Immunodeficiency Virus Infection Predicted by Elevated Cerebrospinal Fluid Levels of Human Immunodeficiency Virus RNA
Ronald J. Ellis, MD, PhD;
David J. Moore, BS;
Meredith E. Childers, MA;
Scott Letendre, MD;
J. Allen McCutchan, MD;
Tanya Wolfson, MA;
Stephen A. Spector, MD;
Karen Hsia, PhD;
Robert K. Heaton, PhD;
Igor Grant, MD;
for the HNRC Group
Arch Neurol. 2002;59:923-928.
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.
From the Department of Neurosciences (Dr Ellis and Ms Childers), HIV
Neurobehavioral Research Center (HNRC) (Drs Ellis, Letendre, McCutchan, Heaton,
and Grant, Mr Moore, and Mss Childers and Wolfson), and Departments of Psychiatry
(Mr Moore and Drs Heaton and Grant), Medicine (Drs Letendre and McCutchan),
and Pediatrics (Drs Spector and Hsia), University of California, San Diego
(UCSD); San Diego State University/UCSD Joint Doctoral Program in Clinical
Psychology (Mr Moore); and Veterans Affairs Healthcare System (Dr Grant),
San Diego. The San Diego HNRC Group is affiliated with the University of California,
San Diego, the Naval Hospital, San Diego, and the San Diego Veterans Affairs
Healthcare System.
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