Effects of central nervous system antiretroviral penetration on cognitive functioning in the ALLRT cohort.

TitleEffects of central nervous system antiretroviral penetration on cognitive functioning in the ALLRT cohort.
Publication TypeJournal Article
Year of Publication2011
AuthorsSmurzynski M, Wu K, Letendre S, Robertson K, Bosch RJ, Clifford DB, Evans S, Collier AC, Taylor M, Ellis R
JournalAIDS
Volume25
Issue3
Pagination357-65
Date Published2011 Jan 28
ISSN1473-5571
KeywordsAdult, Anti-HIV Agents, CD4 Lymphocyte Count, Central Nervous System, Cognition, Female, HIV Infections, HIV-1, Humans, Male, Middle Aged, Neuropsychological Tests, RNA, Viral, Viral Load
Abstract

OBJECTIVE: Differences in antiretroviral distribution into the central nervous system (CNS) may impact neurocognitive status. We assessed the relationship between estimates of antiretroviral therapy penetration into the CNS, using a published ranking system, and neurocognitive status in HIV-positive participants with plasma HIV-1 RNA (vRNA) suppression.

DESIGN: Participants with at least 6 weeks ongoing antiretroviral drug use and vRNA less than 50 copies/ml (N = 2636; 83% male, median baseline CD4 T cells: 244 cells/μl) had at least one neuroscreen assessment [Trail Making Test, Part A and B; Wechsler Adult Intelligence Scale-Revised (WAIS-R) Digit Symbol] at 10 413 neurovisits. Neuroscreen test scores were demographically adjusted and converted to Z-scores (NPZ3: lower scores imply more impairment). Central nervous system penetration effectiveness (CPE) ranks of 0.0 (low), 0.5 (medium), or 1.0 (high) were assigned to antiretrovirals and summed per regimen, per neurovisit.

METHODS: Multivariate linear regression models using generalized estimating equations assessed NPZ3 scores with respect to antiretroviral regimen. Covariates were retained if P ≤ 0.1.

RESULTS: A final model demonstrated that better NPZ3 scores were associated with higher CPE among participants taking more than three antiretroviral drugs (+0.07 per one unit increase in CPE score; P = 0.004) but not among participants with three or less antiretroviral drugs in the regimen (+0.01; P = 0.5). Results were adjusted for demographics, injection drug use, hepatitis C virus serostatus, CD4 cell count (current and nadir), baseline vRNA, antiretroviral experience, and years since first antiretroviral drug use.

CONCLUSION: Use of antiretroviral drugs with better estimated CNS penetration may be associated with better neurocognitive functioning; some people may require more than three antiretroviral drugs to treat HIV in the CNS. Clinically this means antiretroviral regimens could be designed to optimize estimated CNS penetration without sacrificing virologic and immunologic benefits.

DOI10.1097/QAD.0b013e32834171f8
Alternate JournalAIDS
PubMed ID21124201
PubMed Central IDPMC3022370
Grant List1 U01 AI068634 / AI / NIAID NIH HHS / United States
5 U01 AI38855 / AI / NIAID NIH HHS / United States
AI069434 / AI / NIAID NIH HHS / United States
AI069495 / AI / NIAID NIH HHS / United States
NS32228 / NS / NINDS NIH HHS / United States
P30 MH62512 / MH / NIMH NIH HHS / United States
R01 MH58076 / MH / NIMH NIH HHS / United States
U01 AI038855 / AI / NIAID NIH HHS / United States
U01 AI038855-08 / AI / NIAID NIH HHS / United States
U01 AI038855-09 / AI / NIAID NIH HHS / United States
U01 AI038855-09S1 / AI / NIAID NIH HHS / United States
U01 AI038855-09S2 / AI / NIAID NIH HHS / United States
U01AI068636 / AI / NIAID NIH HHS / United States