title: Lithium therapy for human immunodeficiency virus type 1-associated neurocognitive impairment.
abstract: The objective of this study was to assess lithium safety and tolerability and to explore its impact on cognition, function, and neuroimaging biomarkers in human immunodeficiency virus (HIV)-infected subjects with cognitive impairment. Fifteen cognitively impaired HIV-infected subjects were enrolled in this 10-week open-label study of lithium 300 mg twice daily. Neuroimaging was performed at baseline and following 10 weeks of treatment and included magnetic resonance spectroscopy (MRS), diffusion tensor imaging (DTI), and functional MRI (fMRI). Thirteen of the 14 subjects (93%) that complied with the study visits were able to complete the study on lithium and 11 out of 13 (79%) completed the study at the originally assigned dose of 300 mg twice daily. There were no significant changes in CD4(+) lymphocyte cell count and plasma HIV RNA. Cognitive performance and depressive mood did not improve significantly after the 10-week lithium treatment; however, neuroimaging revealed a decrease in the glutamate+glutamine (Glx) peak in the frontal gray matter, increased fractional anisotropy, and decreased mean diffusivity in several brain areas, and changes in brain activation patterns, suggestive of improvement. These results suggest that lithium can be used safely in HIV-infected individuals with cognitive impairment. Furthermore, the neuroimaging results suggest that lithium may improve HIV-associated central nervous system (CNS) injury; thus, further investigations of lithium as an adjunctive treatment for HIV-associated cognitive impairment are warranted.
authors.affiliation: Department of Neurology, University of Rochester, Rochester, New York, USA. giovanni.schifitto@ctcc.rochester.edu
authors.forename: Giovanni
authors.initials: G
authors.lastname: Schifitto
authors.forename: Jianhui
authors.initials: J
authors.lastname: Zhong
authors.forename: David
authors.initials: D
authors.lastname: Gill
authors.forename: Derick R
authors.initials: DR
authors.lastname: Peterson
authors.forename: Michelle D
authors.initials: MD
authors.lastname: Gaugh
authors.forename: Tong
authors.initials: T
authors.lastname: Zhu
authors.forename: Madalina
authors.initials: M
authors.lastname: Tivarus
authors.forename: Kim
authors.initials: K
authors.lastname: Cruttenden
authors.forename: Sanjay B
authors.initials: SB
authors.lastname: Maggirwar
authors.forename: Howard E
authors.initials: HE
authors.lastname: Gendelman
authors.forename: Stephen
authors.initials: S
authors.lastname: Dewhurst
authors.forename: Harris A
authors.initials: HA
authors.lastname: Gelbard
mesh_terms: D000328:Adult; D000928:Antidepressive Agents / Q000008:administration & dosage / Q000009:adverse effects; D001921:Brain / Q000473:pathology; D018791:CD4 Lymphocyte Count; D003072:Cognition Disorders / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D005260:Female; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy* / Q000276:immunology; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D018020:Lithium Compounds / Q000008:administration & dosage* / Q000009:adverse effects; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D016896:Treatment Outcome; D019562:Viral Load
chemical_list: D000928:Antidepressive Agents; D018020:Lithium Compounds