Document Detail


Antiretroviral monocyte efficacy score linked to cognitive impairment in HIV.
MedLine Citation:
PMID:  23018140     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: Monocytes transmigrating to the brain play a central role in HIV neuropathology. We hypothesized that the continued existence of neurocognitive impairment (NCI) despite potent antiretroviral (ARV) therapy is mediated by the inability of such therapy to control this monocyte/macrophage reservoir.
METHODS: Cross-sectional and longitudinal analyses were conducted within a prospectively enrolled cohort. We devised a monocyte efficacy (ME) score based on the anticipated effectiveness of ARV medications against monocytes/macrophages using published macrophage in vitro drug efficacy data. We examined, within an HIV neurocognitive database, its association with composite neuropsychological test scores (NPZ8) and clinical cognitive diagnoses among subjects on stable ARV medications unchanged for >6 months prior to assessment.
RESULTS: Among 139 subjects on ARV therapy, higher ME score correlated with better NPZ8 performance (r=0.23, P<0.01), whereas a score devised to quantify expected penetration effectiveness of ARVs into the brain (CPE score) did not (r=0.12, P=0.15). In an adjusted model (adjusted r(2)=0.12), ME score (β=0.003, P=0.02), CD4(+) T-cell nadir (β=0.001, P<0.01) and gender (β=-0.456, P=0.02) were associated with NPZ8, whereas CPE score was not (β=0.003, P=0.94). A higher ME score was associated with better clinical cognitive status (P<0.01). With a range of 12.5-433.0 units, a 100-unit increase in ME score resulted in a 10.6-fold decrease in the odds of a dementia diagnosis compared with normal cognition (P=0.01).
CONCLUSIONS: ARV efficacy against monocytes/macrophages correlates with cognitive function in HIV-infected individuals on ARV therapy within this cohort. If validated, efficacy against monocytes/macrophages may provide a new target to improve HIV NCI.
Authors:
Cecilia M Shikuma; Beau Nakamoto; Bruce Shiramizu; Chin-Yuan Liang; Victor DeGruttola; Kara Bennett; Robert Paul; Kalpana Kallianpur; Dominic Chow; Christina Gavegnano; Selwyn J Hurwitz; Raymond F Schinazi; Victor G Valcour
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, Non-P.H.S.     Date:  2012-09-28
Journal Detail:
Title:  Antiviral therapy     Volume:  17     ISSN:  2040-2058     ISO Abbreviation:  Antivir. Ther. (Lond.)     Publication Date:  2012  
Date Detail:
Created Date:  2012-11-15     Completed Date:  2013-04-26     Revised Date:  2014-03-19    
Medline Journal Info:
Nlm Unique ID:  9815705     Medline TA:  Antivir Ther     Country:  England    
Other Details:
Languages:  eng     Pagination:  1233-42     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
AIDS Dementia Complex / pathology,  virology
Adult
Anti-Retroviral Agents / metabolism,  pharmacology
CD4 Lymphocyte Count
Cognition
Cognition Disorders / pathology*,  virology
Cross-Sectional Studies
Female
HIV Infections / metabolism,  pathology,  virology
HIV-1 / metabolism,  pathogenicity*
Humans
Longitudinal Studies
Macrophages / drug effects*,  metabolism
Male
Middle Aged
Monocytes / drug effects*,  metabolism
Neuropsychological Tests
Predictive Value of Tests
Prospective Studies
Statistics, Nonparametric
Grant Support
ID/Acronym/Agency:
2P30AI050409/AI/NIAID NIH HHS; K23 AG032872/AG/NIA NIH HHS; K23AG032872/AG/NIA NIH HHS; P30 AI050409/AI/NIAID NIH HHS; R01 NS053345/NS/NINDS NIH HHS; R01 NS061696/NS/NINDS NIH HHS; R01NS053345/NS/NINDS NIH HHS; R01NS061696/NS/NINDS NIH HHS; U19MH081835/MH/NIMH NIH HHS; U54 NS043049/NS/NINDS NIH HHS; U54 RR026136/RR/NCRR NIH HHS; U54NS43049/NS/NINDS NIH HHS; U54RR026136/RR/NCRR NIH HHS
Chemical
Reg. No./Substance:
0/Anti-Retroviral Agents
Comments/Corrections
Comment In:
Antivir Ther. 2012;17(7):1227-31   [PMID:  23018178 ]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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