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Patterns of white matter injury in HIV infection after partial immune reconstitution: a DTI tract-based spatial statistics study

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Abstract

HIV-infected individuals with severe immune suppression are more likely to develop HIV-associated neurocognitive disorders than those with preserved immune function. While partial immune reconstitution occurs in those with severe immune suppression after starting combined antiretroviral therapy, it is not established whether improvement in immune function reverses or prevents injury to the central nervous system (CNS). To address this question, 50 participants (nadir CD4 counts ≤200 cells/mm3, on a stable antiretroviral regimen for at least 12 consecutive weeks prior to study) and 13 HIV negative participants underwent a comprehensive neurological evaluation followed by diffusion tensor imaging (DTI). Eighty-four percent of the 50 HIV participants were neurologically asymptomatic (HIVNA) and 16 % had mild cognitive impairment (HIVCI). Tract-based spatial statistics (TBSS) on DTI data revealed that mean diffusivity (MD) increased significantly in the posterior aspect of both hemispheres in HIVNA compared to controls. In HIVCI, compared to controls and HIVNA, increased MD extended to prefrontal areas. Fractional anisotropy decreased only in HIVCI, compared to either controls or HIVNA. Furthermore, DTI showed significant correlations to duration of HIV infection and significant associations with multiple cognitive domains. This study highlights that in partial immune reconstitution, injury to the CNS is present even in those that are neurologically asymptomatic and there are discrete spatial patterns of white matter injury in HIVNA subjects compared to HIVCI subjects. Our results also show that quantitative analysis of DTI using TBSS is a sensitive approach to evaluate HIV-associated white matter disease and thus valuable in monitoring central nervous system injury.

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Acknowledgments

The project described in this publication was supported by NS036524 and the University of Rochester CTSA award number UL1 RR024160 from the National Center for Research Resources and the National Center for Advancing Translational Sciences of the National Institutes of Health. The authors appreciate useful discussions with Dr. Wei Tian of the Department of Imaging Sciences at the University of Rochester.

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Authors and Affiliations

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

    Tong Zhu, Jianhui Zhong, Madalina Tivarus, Sven Ekholm & Giovanni Schifitto

  2. Department of Biostatistics and Computational Biology, University of Rochester, Rochester, NY, USA

    Rui Hu

  3. Department of Neurology, University of Rochester, 1325 Mount Hope Avenue, Suite 160, Rochester, NY, 14620, USA

    Giovanni Schifitto

  4. Division of Biostatistics, Indiana University School of Medicine, Indianapolis, IN, USA

    Jaroslaw Harezlak

  5. Department of Statistics, University of California at Irvine, Irvine, CA, USA

    Hernando Ombao

  6. Tufts University School of Medicine, Boston, MA, USA

    Bradford Navia

  7. Brown University, Providence, RI, USA

    Ron Cohen

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  1. Tong Zhu
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Correspondence to Giovanni Schifitto.

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Zhu, T., Zhong, J., Hu, R. et al. Patterns of white matter injury in HIV infection after partial immune reconstitution: a DTI tract-based spatial statistics study. J. Neurovirol. 19, 10–23 (2013). https://doi.org/10.1007/s13365-012-0135-9

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  • DOI: https://doi.org/10.1007/s13365-012-0135-9

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