Back to Search
Start Over
HIV DNA reservoir increases risk for cognitive disorders in cART-naïve patients.
- Source :
-
PloS one [PLoS One] 2013 Jul 31; Vol. 8 (7), pp. e70164. Date of Electronic Publication: 2013 Jul 31 (Print Publication: 2013). - Publication Year :
- 2013
-
Abstract
- Objectives: Cognitive impairment remains frequent in HIV, despite combination antiretroviral therapy (cART). Leading theories implicate peripheral monocyte HIV DNA reservoirs as a mechanism for spread of the virus to the brain. These reservoirs remain present despite cART. The objective of this study was to determine if the level of HIV DNA in CD14(+) enriched monocytes predicted cognitive impairment and brain injury.<br />Methods: We enrolled 61 cART-naïve HIV-infected Thais in a prospective study and measured HIV DNA in CD14(+) enriched monocyte samples in a blinded fashion. We determined HAND diagnoses by consensus panel and all participants underwent magnetic resonance spectroscopy (MRS) to measure markers of brain injury. Immune activation was measured via cytokines in cerebrospinal fluid (CSF).<br />Results: The mean (SD) age was 35 (6.9) years, CD4 T-lymphocyte count was 236 (139) and log10 plasma HIV RNA was 4.8 (0.73). Twenty-eight of 61 met HAND criteria. The log10 CD14(+) HIV DNA was associated with HAND in unadjusted and adjusted models (p = 0.001). There was a 14.5 increased odds ratio for HAND per 1 log-value of HIV DNA (10-fold increase in copy number). Plasma CD14(+) HIV DNA was associated with plasma and CSF neopterin (p = 0.023) and with MRS markers of neuronal injury (lower N-acetyl aspartate) and glial dysfunction (higher myoinositol) in multiple brain regions.<br />Interpretation: Reservoir burden of HIV DNA in monocyte-enriched (CD14(+)) peripheral blood cells increases risk for HAND in treatment-naïve HIV+ subjects and is directly associated with CSF immune activation and both brain injury and glial dysfunction by MRS.
- Subjects :
- Adult
Brain metabolism
Brain pathology
Brain virology
Cognition Disorders etiology
Cytokines blood
Cytokines cerebrospinal fluid
DNA, Viral genetics
Female
HIV drug effects
HIV genetics
HIV physiology
HIV Infections complications
HIV Infections virology
Host-Pathogen Interactions drug effects
Humans
Lipopolysaccharide Receptors metabolism
Male
Monocytes metabolism
Monocytes pathology
Monocytes virology
Multiplex Polymerase Chain Reaction
Multivariate Analysis
Prospective Studies
ROC Curve
Regression Analysis
Risk Factors
Antiretroviral Therapy, Highly Active
Cognition Disorders diagnosis
DNA, Viral metabolism
HIV Infections drug therapy
Subjects
Details
- Language :
- English
- ISSN :
- 1932-6203
- Volume :
- 8
- Issue :
- 7
- Database :
- MEDLINE
- Journal :
- PloS one
- Publication Type :
- Academic Journal
- Accession number :
- 23936155
- Full Text :
- https://doi.org/10.1371/journal.pone.0070164