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Neurocognitive Impairment Is an Independent Risk Factor for Death in HIV Infection
Ronald J. Ellis, MD, PhD;
Reena Deutsch, PhD;
Robert K. Heaton, PhD;
Thomas D. Marcotte, PhD;
J. Allen McCutchan, MD;
Julie A. Nelson;
Ian Abramson, PhD;
Leon J. Thal, MD;
J. Hampton Atkinson, MD;
Mark R. Wallace, MD;
Igor Grant, MD;
San Diego HIV Neurobehavioral Research Center Group
Arch Neurol. 1997;54(4):416-424.
Abstract
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Objective
To determine if mortality is increased in individuals with human immunodeficiency virus type 1 (HIV-1)-associated neurocognitive disorders less severe than frank dementia.
Design
A prospective cohort study; median duration of follow-up was 2.4 years. Kaplan-Meier analysis and Cox proportional hazards models were used to compare survival times according to neurocognitive classification.
Setting
University-based research unit.
Participants
A volunteer sample of 414 individuals seropositive for HIV-1. Subjects were classified at their base-line evaluation as neuropsychologically (NP) normal or abnormal (impaired in  2 NP test domains). A subgroup of NP abnormal subjects met operational criteria for HIV-associated minor cognitive motor disorder; the remaining subjects were designated NP impaired. Subjects with frank dementia were excluded.
Main Outcome Measure
Mortality.
Results
At the baseline evaluation, 256 (62%) of 414 subjects were designated normal; 109 (26%), NP impaired; and 49 (12%), minor cognitive motor disorder. One hundred six participants (26%) died during follow-up. Compared with the NP normal group, the unadjusted relative risk (RR) of death for all NP abnormal subjects (minor cognitive motor disorder and NP impaired) was significantly increased (RR, 1.7; 95% confidence interval [CI], 1.2-2.6; P<.005). After adjusting for concurrently measured predictors of survival (CD4 lymphocyte counts, Centers for Disease Control and Prevention HIV disease classification, hemoglobin concentration, and serum β2-microglobulin) in proportional hazards models, mortality for all NP abnormal subjects remained elevated (RR, 1.8; 95% CI, 1.2-2.8; P<.01). The elevation in mortality risk for subjects with minor cognitive motor disorder was statistically significant (RR, 2.2; 95% CI, 1.2-3.8; P<.01); for NP impaired subjects it was marginally significant (RR, 1.6; 95% CI, 1.0-2.8; P=.06).
Conclusions
The HIV-infected individuals with NP impairment had a higher risk of dying than those without impairment. This was particularly true for those meeting syndromic diagnostic criteria.
Author Affiliations
From the Departments of Neurosciences (Drs Ellis and Thai), Psychiatry (Drs Heaton, Marcotte, Atkinson, and Grant), Medicine (Dr McCutchan), and Mathematics (Drs Deutsch and Abramson), University of California, Department of Medicine, Naval Hospital of San Diego (Dr Wallace), and San Diego Veterans Affairs Medical Center (Ms Nelson and Drs Thai and Grant), San Diego, Calif. A complete list of the members of the San Diego HIV Neurobehavioral Research Center Group appears at the end of this article.
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