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Progressive brain atrophy in chronically infected and treated HIV+ individuals

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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.

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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).

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Author notes

  1. Paul M. Thompson and Bradford A. Navia contributed equally to this work.

Authors and Affiliations

  1. Imaging Genetics Center, Mark and Mary Stevens Neuroimaging and Informatics Institute, Keck School of Medicine, University of Southern California, 4676 Admiralty Way Suite 200, Marina del Rey, Los Angeles, CA, 90292, USA

    Talia M. Nir, Neda Jahanshad, Christopher R. K. Ching, Hei Y. Lam, Xue Hua & Paul M. Thompson

  2. Graduate Interdepartmental Program in Neuroscience, UCLA School of Medicine, Los Angeles, CA, USA

    Christopher R. K. Ching

  3. Department of Aging and Geriatric Research, University of Florida, Gainesville, FL, USA

    Ronald A. Cohen

  4. Indiana University School of Public Health, Bloomington, IN, USA

    Jaroslaw Harezlak

  5. Department of Neurology, University of Rochester, Rochester, NY, USA

    Giovanni Schifitto

  6. Department of Imaging Sciences, University of Rochester, Rochester, NY, USA

    Jianhui Zhong

  7. Department Radiation Oncology, University of North Carolina, Chapel Hill, NC, USA

    Tong Zhu

  8. Department of Psychiatry, University of California, San Diego, CA, USA

    Michael J. Taylor

  9. Medicine/Infectious Diseases, University of Colorado Denver, Aurora, CO, USA

    Thomas B. Campbell

  10. Los Angeles Biomedical Research Institute, Harbor-UCLA Medical Center, University of California, Los Angeles, CA, USA

    Eric S. Daar

  11. Department of Neurology, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA

    Elyse J. Singer & Jeffry R. Alger

  12. Department of Public Health, Infection Unit, Tufts University School of Medicine, Boston, MA, USA

    Bradford A. Navia

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  1. Talia M. Nir
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  2. Neda Jahanshad
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  5. Jaroslaw Harezlak
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  6. Giovanni Schifitto
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  7. Hei Y. Lam
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  8. Xue Hua
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  9. Jianhui Zhong
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  10. Tong Zhu
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  11. Michael J. Taylor
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  12. Thomas B. Campbell
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  13. Eric S. Daar
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  14. Elyse J. Singer
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  16. Paul M. Thompson
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  17. Bradford A. Navia
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On behalf of the HIV Neuroimaging Consortium

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Correspondence to Paul M. Thompson.

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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.

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Nir, T.M., Jahanshad, N., Ching, C.R.K. et al. Progressive brain atrophy in chronically infected and treated HIV+ individuals. J. Neurovirol. 25, 342–353 (2019). https://doi.org/10.1007/s13365-019-00723-4

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