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Impact of combination antiretroviral therapy on cerebrospinal fluid HIV RNA and neurocognitive performance

Marra, Christina Ma; Zhao, Yub; Clifford, David Bc; Letendre, Scottd; Evans, Scottb; Henry, Katherinee; Ellis, Ronald Jf; Rodriguez, Benignog; Coombs, Robert Wh; Schifitto, Giovannii; McArthur, Justin Cj; Robertson, Kevink; for the AIDS Clinical Trials Group 736 Study Team

doi: 10.1097/QAD.0b013e32832c4152
Clinical Science

Objective: To determine whether antiretroviral regimens with good central nervous system (CNS) penetration control HIV in cerebrospinal fluid (CSF) and improve cognition.

Design: Multisite longitudinal observational study.

Setting: Research clinics.

Study participants: One hundred and one individuals with advanced HIV beginning or changing a new potent antiretroviral regimen were enrolled in the study. Data for 79 participants were analyzed. Participants underwent structured history and neurological examination, venipuncture, lumbar puncture, and neuropsychological tests at entry, 24, and 52 weeks.

Intervention: Antiretroviral regimens were categorized as CNS penetration effectiveness (CPE) rank of at least 2 or less than 2. Generalized estimating equations were used to examine associations over the course of the study.

Main outcome measures: Concentration of HIV RNA in CSF and blood and neuropsychological test scores (NPZ4 and NPZ8).

Results: Odds of suppression of CSF HIV RNA were higher when CPE rank was at least 2 than when it was less than 2. Odds of suppression of plasma HIV RNA were not associated with CPE rank. Among participants with impaired neuropsychological performance at entry, those prescribed regimens with a CPE rank of at least 2 or more antiretrovirals had lower composite NPZ4 scores over the course of the study.

Conclusion: Antiretroviral regimens with good CNS penetration, as assessed by CPE rank, are more effective in controlling CSF (and presumably CNS) viral replication than regimens with poorer penetration. In this study, antiretrovirals with good CNS penetration were associated with poorer neurocognitive performance. A larger controlled trial is required before any conclusions regarding the influence of specific antiretrovirals on neurocognitive performance should be made.

aDepartment of Neurology, University of Washington School of Medicine, Seattle, Washington, USA

bStatistical and Data Management Center, Harvard University, Boston, Massachusetts, USA

cDepartment of Neurology, Washington University School of Medicine, Saint Louis, Missouri, USA

dDepartment of Medicine, University of California San Diego, San Diego, California, USA

eDepartment of Neurology, New York University, New York, New York, USA

fDepartment of Neurosciences, University of California San Diego, San Diego, California, USA

gDepartment of Medicine, Case Western Reserve University, Cleveland, Ohio, USA

hDepartments of Medicine and Laboratory Medicine, University of Washington School of Medicine, Seattle, Washington, USA

iDepartments of Neurology and Imaging Sciences, University of Rochester, Rochester, New York, USA

jDepartments of Neurology, Epidemiology and Pathology, Johns Hopkins University, Baltimore, Maryland, USA

kDepartment of Neurology, University of North Carolina Chapel Hill, Chapel Hill, North Carolina, USA.

Received 18 February, 2009

Revised 26 March, 2009

Accepted 27 March, 2009

Correspondence to Christina M. Marra, MD, Professor of Neurology, Adjunct Professor of Medicine (Infectious Diseases), University of Washington School of Medicine, Harborview Medical Center, Box 359775, 325 Ninth Avenue, Seattle, WA 98104, USA. Tel: +1 206 897 5400; fax: +1 206 897 5401; e-mail:

© 2009 Lippincott Williams & Wilkins, Inc.