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CD4 nadir is a predictor of HIV neurocognitive impairment in the era of combination antiretroviral therapy

Ellis, Ronald J.a; Badiee, Jayraana; Vaida, Florina; Letendre, Scotta; Heaton, Robert K.a; Clifford, Davidb; Collier, Ann C.c; Gelman, Benjamind; McArthur, Justine; Morgello, Susanf; McCutchan, J. Allena; Grant, Igorafor the CHARTER Group

doi: 10.1097/QAD.0b013e32834a40cd
Clinical Science

Objective: Despite immune recovery in individuals on combination antiretroviral therapy (CART), the frequency of HIV-associated neurocognitive disorders (HANDs) remains high. Immune recovery is typically achieved after initiation of ART from the nadir, or the lowest historical CD4. The present study evaluated the probability of neuropsychological impairment (NPI) and HAND as a function of CD4 nadir in an HIV-positive cohort.

Methods: One thousand five hundred and twenty-five HIV-positive participants enrolled in CNS HIV Antiretroviral Therapy Effects Research, a multisite, observational study that completed comprehensive neurobehavioral and neuromedical evaluations, including a neurocognitive test battery covering seven cognitive domains. Among impaired individuals, HAND was diagnosed if NPI could not be attributed to comorbidities. CD4 nadir was obtained by self-report or observation. Potential modifiers of the relationship between CD4 nadir and HAND, including demographic and HIV disease characteristics, were assessed in univariate and multivariate analyses.

Results: The median CD4 nadir (cells/μl) was 172, and 52% had NPI. Among impaired participants, 603 (75%) had HAND. Higher CD4 nadirs were associated with lower odds of NPI such that for every 5-unit increase in square-root CD4 nadir, the odds of NPI were reduced by 10%. In 589 virally suppressed participants on ART, higher CD4 nadir was associated with lower odds of NPI after adjusting for demographic and clinical factors.

Conclusion: As the risk of NPI was lowest in patients whose CD4 cell count was never allowed to fall to low levels before CART initiation, our findings suggest that initiation of CART as early as possible might reduce the risk of developing HAND, the most common source of NPI among HIV-infected individuals.

aUniversity of California, San Diego, San Diego, California

bWashington University, St Louis, Missouri

cUniversity of Washington, Seattle, Washington

dUniversity of Texas Medical Branch, Galveston, Texas

eJohns Hopkins University, Baltimore, Maryland

fMount Sinai School of Medicine, New York, New York, USA.

Correspondence to Ronald J. Ellis, MD, PhD, 220 Dickinson Street, Suite B, Mail Code 8231, San Diego, CA 92103-8231, USA. Tel: +1 619 543 5079; fax: +1 619 543 4744; e-mail:

Received 17 March, 2011

Revised 26 May, 2011

Accepted 24 June, 2011

© 2011 Lippincott Williams & Wilkins, Inc.