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Structural brain abnormalities in successfully treated HIV infection : associations with disease and cerebrospinal fluid biomarkers

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Abstract
Background. Brain structural abnormalities have been reported in persons living with human immunodeficiency virus (HIV; PLWH) who are receiving suppressive combination antiretroviral therapy (cART), but their pathophysiology remains unclear. Methods. We investigated factors associated with brain tissue volumes and white matter microstructure (fractional anisotropy) in 134 PLWH receiving suppressive cART and 79 comparable HIV-negative controls, aged >= 45 years, from the Comorbidity in Relation to AIDS cohort, using multimodal neuroimaging and cerebrospinal fluid biomarkers. Results. Compared with controls, PLWH had lower gray matter volumes (-13.7 mL; 95% confidence interval, -25.1 to -2.2) and fractional anisotropy (-0.0073; 95% confidence interval, -. 012 to -. 0024), with the largest differences observed in those with prior clinical AIDS. Hypertension and the soluble CD14 concentration in cerebrospinal fluid were associated with lower fractional anisotropy. These associations were independent of HIV serostatus (P-interaction =.32 and P-interaction =.59, respectively) and did not explain the greater abnormalities in brain structure in relation to HIV infection. Conclusions. The presence of lower gray matter volumes and more white matter microstructural abnormalities in well-treated PLWH partly reflect a combination of historical effects of AIDS, as well as the more general influence of systemic factors, such as hypertension and ongoing neuroinflammation. Additional mechanisms explaining the accentuation of brain structure abnormalities in treated HIV infection remain to be identified.
Keywords
CENTRAL-NERVOUS-SYSTEM, ACTIVE ANTIRETROVIRAL THERAPY, WHITE-MATTER, INTEGRITY, COGNITIVE IMPAIRMENT, SPATIAL STATISTICS, RISK-FACTORS, PROTEIN, MARKER, INDIVIDUALS, TRYPTOPHAN, HIV, neuroimaging, neurofilament light chain, cerebrospinal fluid, biomarkers

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Chicago
van Zoest, Rosan A, Jonathan Underwood, Davide De Francesco, Caroline A Sabin, James H Cole, Ferdinand W Wit, Matthan WA Caan, et al. 2018. “Structural Brain Abnormalities in Successfully Treated HIV Infection : Associations with Disease and Cerebrospinal Fluid Biomarkers.” Journal of Infectious Diseases 217 (1): 69–81.
APA
van Zoest, R. A., Underwood, J., De Francesco, D., Sabin, C. A., Cole, J. H., Wit, F. W., Caan, M. W., et al. (2018). Structural brain abnormalities in successfully treated HIV infection : associations with disease and cerebrospinal fluid biomarkers. JOURNAL OF INFECTIOUS DISEASES, 217(1), 69–81.
Vancouver
1.
van Zoest RA, Underwood J, De Francesco D, Sabin CA, Cole JH, Wit FW, et al. Structural brain abnormalities in successfully treated HIV infection : associations with disease and cerebrospinal fluid biomarkers. JOURNAL OF INFECTIOUS DISEASES. 2018;217(1):69–81.
MLA
van Zoest, Rosan A et al. “Structural Brain Abnormalities in Successfully Treated HIV Infection : Associations with Disease and Cerebrospinal Fluid Biomarkers.” JOURNAL OF INFECTIOUS DISEASES 217.1 (2018): 69–81. Print.
@article{8564387,
  abstract     = {Background. Brain structural abnormalities have been reported in persons living with human immunodeficiency virus (HIV; PLWH) who are receiving suppressive combination antiretroviral therapy (cART), but their pathophysiology remains unclear. 
Methods. We investigated factors associated with brain tissue volumes and white matter microstructure (fractional anisotropy) in 134 PLWH receiving suppressive cART and 79 comparable HIV-negative controls, aged >= 45 years, from the Comorbidity in Relation to AIDS cohort, using multimodal neuroimaging and cerebrospinal fluid biomarkers. 
Results. Compared with controls, PLWH had lower gray matter volumes (-13.7 mL; 95% confidence interval, -25.1 to -2.2) and fractional anisotropy (-0.0073; 95% confidence interval, -. 012 to -. 0024), with the largest differences observed in those with prior clinical AIDS. Hypertension and the soluble CD14 concentration in cerebrospinal fluid were associated with lower fractional anisotropy. These associations were independent of HIV serostatus (P-interaction =.32 and P-interaction =.59, respectively) and did not explain the greater abnormalities in brain structure in relation to HIV infection. 
Conclusions. The presence of lower gray matter volumes and more white matter microstructural abnormalities in well-treated PLWH partly reflect a combination of historical effects of AIDS, as well as the more general influence of systemic factors, such as hypertension and ongoing neuroinflammation. Additional mechanisms explaining the accentuation of brain structure abnormalities in treated HIV infection remain to be identified.},
  author       = {van Zoest, Rosan A and Underwood, Jonathan and De Francesco, Davide and Sabin, Caroline A and Cole, James H and Wit, Ferdinand W and Caan, Matthan WA and Kootstra, Neeltje A and Fuchs, Dietmar and Zetterberg, Henrik and Majoie, Charles BLM and Portegies, Peter and Winston, Alan and Sharp, David J and Gisslen, Magnus and Reiss, Peter and Comorbidity in Relation to AIDS (COBRA) collaboration, on behalf of the and Libert, Claude},
  issn         = {0022-1899},
  journal      = {JOURNAL OF INFECTIOUS DISEASES},
  keywords     = {CENTRAL-NERVOUS-SYSTEM,ACTIVE ANTIRETROVIRAL THERAPY,WHITE-MATTER,INTEGRITY,COGNITIVE IMPAIRMENT,SPATIAL STATISTICS,RISK-FACTORS,PROTEIN,MARKER,INDIVIDUALS,TRYPTOPHAN,HIV,neuroimaging,neurofilament light chain,cerebrospinal fluid,biomarkers},
  language     = {eng},
  number       = {1},
  pages        = {69--81},
  title        = {Structural brain abnormalities in successfully treated HIV infection : associations with disease and cerebrospinal fluid biomarkers},
  url          = {http://dx.doi.org/10.1093/infdis/jix553},
  volume       = {217},
  year         = {2018},
}

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