Impact of combination antiretroviral therapy on cerebrospinal fluid HIV RNA and neurocognitive performance.
OBJECTIVE
To determine whether antiretroviral regimens with good central nervous system (CNS) penetration control HIV in cerebrospinal fluid (CSF) and improve cognition.


METHODS
Multisite longitudinal observational study.


METHODS
Research clinics.


METHODS
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.


METHODS
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.


METHODS
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.


CONCLUSIONS
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.
Marra
Christina M
CM
Department of Neurology, University of Washington School of Medicine, Seattle, USA. cmarra@u.washington.edu
Zhao
Yu
Y
Clifford
David B
DB
Letendre
Scott
S
Evans
Scott
S
Henry
Katherine
K
Ellis
Ronald J
RJ
Rodriguez
Benigno
B
Coombs
Robert W
RW
Schifitto
Giovanni
G
McArthur
Justin C
JC
Robertson
Kevin
K
D000328:Adult; D019380:Anti-HIV Agents / Q000134:cerebrospinal fluid / Q000627:therapeutic use*; D003071:Cognition / Q000187:drug effects*; D004812:Epidemiologic Methods; D005260:Female; D006678:HIV; D015658:HIV Infections / Q000134:cerebrospinal fluid / Q000188:drug therapy*; D017320:HIV Protease Inhibitors / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D012367:RNA, Viral / Q000134:cerebrospinal fluid*
D019380:Anti-HIV Agents; D017320:HIV Protease Inhibitors; D012367:RNA, Viral