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Progressive brain atrophy in chronically infected and treated HIV+ individuals

  • Talia M. Nir
  • Neda Jahanshad
  • Christopher R. K. Ching
  • Ronald A. Cohen
  • Jaroslaw Harezlak
  • Giovanni Schifitto
  • Hei Y. Lam
  • Xue Hua
  • Jianhui Zhong
  • Tong Zhu
  • Michael J. Taylor
  • Thomas B. Campbell
  • Eric S. Daar
  • Elyse J. Singer
  • Jeffry R. Alger
  • Paul M. ThompsonEmail author
  • Bradford A. Navia
  • On behalf of the HIV Neuroimaging Consortium
Article
  • 158 Downloads

Abstract

Growing evidence points to persistent neurological injury in chronic HIV infection. It remains unclear whether chronically HIV-infected individuals on combined antiretroviral therapy (cART) develop progressive brain injury and impaired neurocognitive function despite successful viral suppression and immunological restoration. In a longitudinal neuroimaging study for the HIV Neuroimaging Consortium (HIVNC), we used tensor-based morphometry to map the annual rate of change of regional brain volumes (mean time interval 1.0 ± 0.5 yrs), in 155 chronically infected and treated HIV+ participants (mean age 48.0 ± 8.9 years; 83.9% male) . We tested for associations between rates of brain tissue loss and clinical measures of infection severity (nadir or baseline CD4+ cell count and baseline HIV plasma RNA concentration), HIV duration, cART CNS penetration-effectiveness scores, age, as well as change in AIDS Dementia Complex stage. We found significant brain tissue loss across HIV+ participants, including those neuro-asymptomatic with undetectable viral loads, largely localized to subcortical regions. Measures of disease severity, age, and neurocognitive decline were associated with greater atrophy. Chronically HIV-infected and treated individuals may undergo progressive brain tissue loss despite stable and effective cART, which may contribute to neurocognitive decline. Understanding neurological complications of chronic infection and identifying factors associated with atrophy may help inform strategies to maintain brain health in people living with HIV.

Keywords

HIV ADC MRI Brain volume cART TBM 

Notes

Acknowledgments

The study was funded by NIH NINDS R01 NS080655 and U54 EB020403. Data used in the preparation of this article were obtained from the Parkinson’s Progression Markers Initiative (PPMI) database (www.ppmi-info.org/data). For up-to-date information on the study, visit www.ppmi-info.org . PPMI—a public-private partnership—is funded by the Michael J. Fox Foundation for Parkinson’s Research and funding partners, including AbbVie, Allergan, Avid Radiopharmaceuticals, Biogen, BioLegend, Bristol-Myers Squibb, Denali, GE Healthcare, Genentech, GlaxoSmithKline (GSK), Eli Lilly and Company, Lundbeck, Merck, Meso Scale Discovery (MSD), Pfizer, Piramal Imaging, Roche, Sanofi Genzyme, Servier, Takeda, Teva, and UCB (www.ppmi-info.org/fundingpartners).

Compliance with ethical standards

Conflict of interest

Jeffry R Alger owns NeuroSpectroScopics LLC. Thomas B Campbell is a consultant for Gilead Sciences and Theratechnologies Inc. Xue Hua now works for M3 Biotechnology; the work included in the manuscript was conducted during her appointment at USC, and she reports no disclosures. The remaining authors declare that they have no conflict of interest.

Supplementary material

13365_2019_723_MOESM1_ESM.pdf (229 kb)
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Copyright information

© Journal of NeuroVirology, Inc. 2019

Authors and Affiliations

  • Talia M. Nir
    • 1
  • Neda Jahanshad
    • 1
  • Christopher R. K. Ching
    • 1
    • 2
  • Ronald A. Cohen
    • 3
  • Jaroslaw Harezlak
    • 4
  • Giovanni Schifitto
    • 5
  • Hei Y. Lam
    • 1
  • Xue Hua
    • 1
  • Jianhui Zhong
    • 6
  • Tong Zhu
    • 7
  • Michael J. Taylor
    • 8
  • Thomas B. Campbell
    • 9
  • Eric S. Daar
    • 10
  • Elyse J. Singer
    • 11
  • Jeffry R. Alger
    • 11
  • Paul M. Thompson
    • 1
    Email author
  • Bradford A. Navia
    • 12
  • On behalf of the HIV Neuroimaging Consortium
  1. 1.Imaging Genetics Center, Mark and Mary Stevens Neuroimaging and Informatics Institute, Keck School of MedicineUniversity of Southern CaliforniaLos AngelesUSA
  2. 2.Graduate Interdepartmental Program in NeuroscienceUCLA School of MedicineLos AngelesUSA
  3. 3.Department of Aging and Geriatric ResearchUniversity of FloridaGainesvilleUSA
  4. 4.Indiana University School of Public HealthBloomingtonUSA
  5. 5.Department of NeurologyUniversity of RochesterRochesterUSA
  6. 6.Department of Imaging SciencesUniversity of RochesterRochesterUSA
  7. 7.Department Radiation OncologyUniversity of North CarolinaChapel HillUSA
  8. 8.Department of PsychiatryUniversity of CaliforniaSan DiegoUSA
  9. 9.Medicine/Infectious DiseasesUniversity of Colorado DenverAuroraUSA
  10. 10.Los Angeles Biomedical Research Institute, Harbor-UCLA Medical CenterUniversity of CaliforniaLos AngelesUSA
  11. 11.Department of NeurologyDavid Geffen School of Medicine at UCLALos AngelesUSA
  12. 12.Department of Public Health, Infection UnitTufts University School of MedicineBostonUSA

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