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

TitleImpact of combination antiretroviral therapy on cerebrospinal fluid HIV RNA and neurocognitive performance.
Publication TypeJournal Article
Year of Publication2009
AuthorsMarra CM, Zhao Y, Clifford DB, Letendre S, Evans S, Henry K, Ellis RJ, Rodriguez B, Coombs RW, Schifitto G, McArthur JC, Robertson K
Corporate AuthorsAIDS Clinical Trials Group 736 Study Team
JournalAIDS
Volume23
Issue11
Pagination1359-66
Date Published2009 Jul 17
ISSN1473-5571
KeywordsAdult, Anti-HIV Agents, Cognition, Epidemiologic Methods, Female, HIV, HIV Infections, HIV Protease Inhibitors, Humans, Male, Middle Aged, Neuropsychological Tests, RNA, Viral
Abstract

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.

DOI10.1097/QAD.0b013e32832c4152
Alternate JournalAIDS
PubMed ID19424052
PubMed Central IDPMC2706549
Grant List5-MO1 RR00044 / RR / NCRR NIH HHS / United States
5-P30-AI-045008-07 / AI / NIAID NIH HHS / United States
AI -69532 / AI / NIAID NIH HHS / United States
AI 69415 / AI / NIAID NIH HHS / United States
AI 69434 / AI / NIAID NIH HHS / United States
AI-27757 / AI / NIAID NIH HHS / United States
AI-38858 / AI / NIAID NIH HHS / United States
AI-69465 / AI / NIAID NIH HHS / United States
AI34853 / AI / NIAID NIH HHS / United States
AI38858 / AI / NIAID NIH HHS / United States
AI50410 / AI / NIAID NIH HHS / United States
AI69423 / AI / NIAID NIH HHS / United States
AI69432 / AI / NIAID NIH HHS / United States
AI69467 / AI / NIAID NIH HHS / United States
AI69471 / AI / NIAID NIH HHS / United States
AI69472 / AI / NIAID NIH HHS / United States
AI69474 / AI / NIAID NIH HHS / United States
AI69495 / AI / NIAID NIH HHS / United States
AI69501 / AI / NIAID NIH HHS / United States
AI69511 / AI / NIAID NIH HHS / United States
M01RR00096 / RR / NCRR NIH HHS / United States
NS32228 / NS / NINDS NIH HHS / United States
RR-00052 / RR / NCRR NIH HHS / United States
RR00046 / RR / NCRR NIH HHS / United States
U01 AI038858 / AI / NIAID NIH HHS / United States
U01 AI038858-07 / AI / NIAID NIH HHS / United States
U01 AI068636 / AI / NIAID NIH HHS / United States
U01 AI068636-01 / AI / NIAID NIH HHS / United States
U01AI068636 / AI / NIAID NIH HHS / United States