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Published on: January 12, 2016
Neurocognitive Dysfunction With Neuronal Injury in People With HIV on Long-Duration Antiretroviral Therapy
Cynthia McMahan1, Devon K Dietrich1, Elizabeth F Horne1
1From the Section of Infections of the Nervous System (C.M., D.K.D., E.F.H., E.K., K.G., P.S.S.J., A.N., B.R.S.), Office of the Clinical Director (T.W.),, and Translational Neuroradiology Section (D.S.R., G.N.), National Institute of Neurological Disorders and Stroke, NIH, Bethesda, MD; University of Pittsburgh School of Medicine (C.M.), PA; Duke University School of Medicine (E.F.H.), Durham, NC; Virginia Commonwealth University School of Medicine (E.K.), Richmond; Department of Neurology (K.G.), Case Western Reserve University/University Hospitals Cleveland Medical Center, OH; Department of Psychiatry (P.S.S.J.), Washington University School of Medicine, St. Louis, MO; Office of the Clinical Director (L.H., J.S.), National Institute of Mental Health, NIH, Bethesda, MD; San Diego State University/University of California San Diego Joint Doctoral Program in Clinical Psychology (L.H.); Leidos Biomedical Research (U.S.), Frederick, MD; HIV Dynamics and Replication Program (C.-Y.L.), NCI, NIH, Bethesda, Infectious Diseases Clinical Research Program (H.-C.H., A.G., B.K.A.), Department of Preventive Medicine and Biostatistics, Uniformed Services University of the Health Sciences, Bethesda,; The Henry M. Jackson Foundation for the Advancement of Military Medicine (H.-C.H., A.G., B.K.A.), Bethesda,; Department of Medicine (A.G., B.K.A.), Uniformed Services University, Bethesda, MD; Division of Infectious Diseases (C.B.), Naval Medical Center San Diego, CA; and Department of Psychiatry and the Behavioral Sciences (S.K.), University of Southern California Keck School of Medicine, Los Angeles.
People with HIV on long-duration antiretroviral therapy show cognitive deficits and mood issues, with brain changes indicating ongoing injury and inflammation. Further research is needed to understand these long-term neurologic outcomes.
Area of Science:
- Neurology
- Neuroimmunology
- Infectious Diseases
Background:
- Neurologic outcomes in people with HIV (PWH) on long-duration antiretroviral therapy (ART) remain incompletely understood.
- The underlying pathophysiology of these outcomes requires further elucidation.
Purpose of the Study:
- To investigate the long-term neurologic and psychiatric outcomes in PWH on effective ART.
- To compare cognitive function, mood, and neuroimaging markers between PWH and HIV-negative controls.
Main Methods:
- An observational study comparing 155 PWH on ART for ≥15 years with 100 HIV-negative controls.
- Utilized Coarsened Exact Matching for group comparability, followed by cognitive testing, psychiatric assessments, MRI, and CSF analysis.
- Employed weighted regression models to assess the impact of HIV on various outcomes.
Main Results:
- PWH demonstrated lower scores in attention/working memory, motor function, and information processing speed compared to controls.
- PWH reported more cognitive difficulties, depressive symptoms, anxiety, and psychiatric medication use.
- MRI revealed reduced subcortical gray matter, while CSF showed elevated neurofilament light chain and TNF-α, indicating neuroinflammation and neuronal injury.
Conclusions:
- Despite effective long-term ART, PWH exhibit significant neurocognitive deficits and mood disturbances.
- Neuroimaging and CSF findings suggest ongoing neuronal injury and neuroinflammation in PWH.
- Longitudinal studies are crucial to understand the implications of these abnormalities in the growing population of virologically controlled PWH.
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