Rosan A van Zoest1, Jonathan Underwood2, Davide De Francesco3, Caroline A Sabin3, James H Cole4, Ferdinand W Wit1,5,6, Matthan W A Caan7, Neeltje A Kootstra8, Dietmar Fuchs9, Henrik Zetterberg10,11,12,13, Charles B L M Majoie7, Peter Portegies14, Alan Winston2, David J Sharp4, Magnus Gisslén15, Peter Reiss1,5,6. 1. Department of Global Health, Academic Medical Center, and Amsterdam Institute for Global Health and Development, Amsterdam, the Netherlands. 2. Division of Infectious Diseases, United Kingdom. 3. Department of Infection and Population Health, United Kingdom. 4. Division of Brain Sciences, Imperial College London, United Kingdom. 5. Division of Infectious Diseases, Department of Internal Medicine, Amsterdam, the Netherlands. 6. HIV Monitoring Foundation, Amsterdam, the Netherlands. 7. Department of Radiology, Amsterdam, the Netherlands. 8. Department of Experimental Immunology, Academic Medical Center, Amsterdam, the Netherlands. 9. Division of Biological Chemistry, Biocenter, Medical University of Innsbruck, Austria. 10. Department of Molecular Neuroscience, Institute of Neurology, United Kingdom. 11. UK Dementia Research Institute, Institute of Neurology, University College London, United Kingdom. 12. Department of Psychiatry and Neurochemistry, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden. 13. Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Gothenburg, Sweden. 14. Department of Neurology, Onze Lieve Vrouwe Gasthuis, Amsterdam, the Netherlands. 15. Department of Infectious Diseases, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
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 (Pinteraction = .32 and Pinteraction = .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.
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 (Pinteraction = .32 and Pinteraction = .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.
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