, Volume 15, Issue 2, pp 187-195

White matter tract injury and cognitive impairment in human immunodeficiency virusinfected individuals

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Approximately half of those infected with the human immunodeficiency virus (HIV) exhibit cognitive impairment, which has been related to cerebral white matter damage. Despite the effectiveness of antiretroviral treatment, cognitive impairment remains common even in individuals with undetectable viral loads. One explanation for this may be subtherapeutic concentrations of some antiretrovirals in the central nervous system (CNS). We utilized diffusion tensor imaging and a comprehensive neuropsychological evaluation to investigate the relationship of white matter integrity to cognitive impairment and antiretroviral treatment variables. Participants included 39 HIV-infected individuals (49% with acquired immunodeficiency syndrome [AIDS]; mean CD4=529) and 25 seronegative subjects. Diffusion tensor imaging indices were mapped onto a common whole-brain white matter tract skeleton, allowing between-subject voxelwise comparisons. The total HIV-infected group exhibited abnormal white matter in the internal capsule, inferior longitudinal fasciculus, and optic radiation; whereas those with AIDS exhibited more widespread damage, including in the internal capsule and the corpus callosum. Cognitive impairment in the HIV-infected group was related to white matter injury in the internal capsule, corpus callosum, and superior longitudinal fasciculus. White matter injury was not found to be associated with HIV viral load or estimated CNS penetration of antiretrovirals. Diffusion tensor imaging was useful in identifying changes in white matter tracts associated with more advanced HIV infection. Relationships between diffusion alterations in specific white matter tracts and cognitive impairment support the potential utility of diffusion tensor imaging in examining the anatomical underpinnings of HIV-related cognitive impairment. The study also confirms that CNS injury is evident in persons infected with HIV despite effective antiretroviral treatment.

The CNS HIV Anti-Retroviral Therapy Effects Research (CHARTER) is supported by award N01MH22005 from the NIH. The CHARTER group is affiliated with the Johns Hopkins University, Mount Sinai School of Medicine, University of California, San Diego, University of Texas, Galveston, University of Washington, Seattle, Washington University, St. Louis, and is headquartered at the University of California, San Diego, and includes Director: Igor Grant, MD; Co-Directors: J. Allen McCutchan, MD, Ronald J. Ellis, MD, PhD, Thomas D. Marcotte, PhD; Center Manager: Donald Franklin, Jr; Neuromedical Component: Ronald J. Ellis, MD, PhD (P.I.), J. Allen McCutchan, MD, Terry Alexander, RN; Laboratory, Pharmacology and Immunology Component: Scott Letendre, MD (P.I.), Edmund Capparelli, PharmD, Janis Durelle; Neurobehavioral Component: Robert K. Heaton, PhD (P.I.), J. Hampton Atkinson, MD, Steven Paul Woods, PsyD, Matthew Dawson; Virology Component: Joseph K. Wong, MD (P.I.), Caroline Ignacio; Imaging Component: Terry Jernigan, PhD (Co-P.I.), Michael J. Taylor, PhD (Co-P.I.), Rebecca Theilmann, PhD; Data Management Unit: Anthony C. Gamst, PhD (P.I.), Clint Cushman; Statistics Unit: Ian Abramson, PhD (P.I.), Chris Ake, PhD, Deborah Lazzaretto, MS; Protocol Coordinating Component: Thomas D. Marcotte, PhD (P.I.), Rodney von Jaeger, MPH; Johns Hopkins University Site: Justin McArthur (P.I.); Mount Sinai School of Medicine Site: Susan Morgello, MD (Co-P.I.) and David Simpson, MD (Co-P.I.); University of California, San Diego, Site: J. Allen McCutchan, MD (P.I.); University of Washington, Seattle, Site: Ann Collier, MD (Co-P.I.) and Christina Marra, MD (Co-P.I.); University of Texas, Galveston, Site: Benjamin Gelman, MD, PhD (P.I.); and Washington University, St. Louis, Site: David Clifford, MD (P.I.), Muhammad Al-Lozi, MD.
The research described was also supported by NIH grants P30MH62512, R01MH64729, R01MH73419, R01MH75870, R24MH59745, and the Alcohol Abuse and Neuropsychological Impairment study at the VA San Diego Healthcare System.
Statistical analysis conducted by A.G. and B.C.S.