Increases in brain white matter abnormalities and subcortical gray matter are linked to CD4 recovery in HIV infection

详细信息    查看全文

• 作者：Christine Fennema-Notestine (1) (2)
  Ronald J. Ellis (4)
  Sarah L. Archibald (1)
  Terry L. Jernigan (1) (2)
  Scott L. Letendre (3)
  Randy J. Notestine (1)
  Michael J. Taylor (1)
  Rebecca J. Theilmann (2)
  Michelle D. Julaton (1)
  David J. Croteau (4)
  Tanya Wolfson (6)
  Robert K. Heaton (1)
  Anthony C. Gamst (5)
  Donald R. Franklin Jr. (1)
  David B. Clifford (7)
  Ann C. Collier (8)
  Benjamin B. Gelman (10)
  Christina Marra (8) (9)
  Justin C. McArthur (11)
  J. Allen McCutchan (3)
  Susan Morgello (12) (13)
  David M. Simpson (13)
  Igor Grant (1)
  
• 关键词：Antiretroviral therapy ; Brain ; CD4+ T cell ; Immune recovery/reconstitution ; Inflammation ; MRI
• 刊名：Journal of NeuroVirology
• 出版年：2013
• 出版时间：August 2013
• 年：2013
• 卷：19
• 期：4
• 页码：393-401
• 全文大小：299KB
• 参考文献：1. Anthony IC, Ramage SN, Carnie FW, Simmonds P, Bell JE (2005) Influence of HAART on HIV-related CNS disease and neuroinflammation. J Neuropathol Exp Neurol 64:529-36
  2. Awad IA, Johnson PC, Spetzler RF, Hodak JA (1986a) Incidental subcortical lesions identified on magnetic resonance imaging in the elderly. II. Postmortem pathological correlations. Stroke 17:1090-097 CrossRef
  3. Awad IA, Spetzler RF, Hodak JA, Awad CA, Carey R (1986b) Incidental subcortical lesions identified on magnetic resonance imaging in the elderly. I. Correlation with age and cerebrovascular risk factors. Stroke 17:1084-089 CrossRef
  4. Awad IA, Spetzler RF, Hodak JA, Awad CA, Williams F Jr, Carey R (1987) Incidental lesions noted on magnetic resonance imaging of the brain: prevalence and clinical significance in various age groups. Neurosurgery 20:222-27 CrossRef
  5. Becker JT, Maruca V, Kingsley LA, Sanders JM, Alger JR, Barker PB, Goodkin K, Martin E, Miller EN, Ragin A, Sacktor N, Selnes O (2011a) Factors affecting brain structure in men with HIV disease in the post-HAART era. Neuroradiology 54(2):113-21. doi:10.1007/s00234-011-0854-2 CrossRef
  6. Becker JT, Sanders J, Madsen SK, Ragin A, Kingsley L, Maruca V, Cohen B, Goodkin K, Martin E, Miller EN, Sacktor N, Alger JR, Barker PB, Saharan P, Carmichael OT, Thompson PM (2011b) Subcortical brain atrophy persists even in HAART-regulated HIV disease. Brain Imaging Behav 5:77-5 CrossRef
  7. Berger JR, Nath A, Greenberg RN, Andersen AH, Greene RA, Bognar A, Avison MJ (2000) Cerebrovascular changes in the basal ganglia with HIV dementia. Neurology 54:921-26 CrossRef
  8. Binquet C, Chene G, Jacqmin-Gadda H, Journot V, Saves M, Lacoste D, Dabis F (2001) Modeling changes in CD4-positive T-lymphocyte counts after the start of highly active antiretroviral therapy and the relation with risk of opportunistic infections: the Aquitaine Cohort, 1996-997. Am J Epidemiol 153:386-93 CrossRef
  9. Cardenas VA, Meyerhoff DJ, Studholme C, Kornak J, Rothlind J, Lampiris H, Neuhaus J, Grant RM, Chao LL, Truran D, Weiner MW (2009) Evidence for ongoing brain injury in human immunodeficiency virus-positive patients treated with antiretroviral therapy. J Neurovirol 15:324-33 CrossRef
  10. Castelo JM, Courtney MG, Melrose RJ, Stern CE (2007) Putamen hypertrophy in nondemented patients with human immunodeficiency virus infection and cognitive compromise. Arch Neurol 64:1275-280 CrossRef
  11. Chang L, Cloak C, Patterson K, Grob C, Miller EN, Ernst T (2005) Enlarged striatum in abstinent methamphetamine abusers: a possible compensatory response. Biol Psychiatry 57:967-74 CrossRef
  12. Cohen RA, Harezlak J, Gongvatana A, Buchthal S, Schifitto G, Clark U, Paul R, Taylor M, Thompson P, Tate D, Alger J, Brown M, Zhong J, Campbell T, Singer E, Daar E, McMahon D, Tso Y, Yiannoutsos CT, Navia B (2010a) Cerebral metabolite abnormalities in human immunodeficiency virus are associated with cortical and subcortical volumes. J Neurovirol 16:435-44
  13. Cohen RA, Harezlak J, Schifitto G, Hana G, Clark U, Gongvatana A, Paul R, Taylor M, Thompson P, Alger J, Brown M, Zhong J, Campbell T, Singer E, Daar E, McMahon D, Tso Y, Yiannoutsos CT, Navia B (2010b) Effects of nadir CD4 count and duration of human immunodeficiency virus infection on brain volumes in the highly active antiretroviral therapy era. J Neurovirol 16:25-2 CrossRef
  14. DeCarli C, Fletcher E, Ramey V, Harvey D, Jagust WJ (2005) Anatomical mapping of white matter hyperintensities (WMH): exploring the relationships between periventricular WMH, deep WMH, and total WMH burden. Stroke 36:50-5 CrossRef
  15. Ellis R, Langford D, Masliah E (2007) HIV and antiretroviral therapy in the brain: neuronal injury and repair. Nat Rev Neurosci 8:33-4 CrossRef
  16. Fazekas F, Kleinert R, Offenbacher H, Schmidt R, Kleinert G, Payer F, Radner H, Lechner H (1993) Pathologic correlates of incidental MRI white matter signal hyperintensities. Neurology 43:1683-689 CrossRef
  17. Fennema-Notestine C, Gamst AC, Quinn BT, Pacheco J, Jernigan TL, Thal L, Buckner R, Killiany R, Blacker D, Dale AM, Fischl B, Dickerson B, Gollub RL (2007) Feasibility of multi-site clinical structural neuroimaging studies of aging using legacy data. Neuroinformatics 5:235-45 CrossRef
  18. Fletcher NF, McKeating JA (2012) Hepatitis C virus and the brain. J Viral Hepat 19:301-06 CrossRef
  19. Goicoechea M, Smith DM, Liu L, May S, Tenorio AR, Ignacio CC, Landay A, Haubrich R (2006) Determinants of CD4+ T cell recovery during suppressive antiretroviral therapy: association of immune activation, T cell maturation markers, and cellular HIV-1 DNA. J Infect Dis 194:29-7 CrossRef
  20. Jacobsen LK, Giedd JN, Gottschalk C, Kosten TR, Krystal JH (2001) Quantitative morphology of the caudate and putamen in patients with cocaine dependence. Am J Psychiatry 158:486-89 CrossRef
  21. Jernigan TL, Archibald SL, Fennema-Notestine C, Taylor MJ, Theilmann RJ, Julaton MD, Notestine RJ, Wolfson T, Letendre SL, Ellis RJ, Heaton RK, Gamst AC, Franklin DR Jr, Clifford DB, Collier AC, Gelman BB, Marra C, McArthur JC, McCutchan JA, Morgello S, Simpson DM, Grant I (2011) Clinical factors related to brain structure in HIV: the CHARTER study. J Neurovirol 17:248-57 CrossRef
  22. Jernigan TL, Gamst AC, Archibald SL, Fennema-Notestine C, Mindt MR, Marcotte TD, Heaton RK, Ellis RJ, Grant I (2005) Effects of methamphetamine dependence and HIV infection on cerebral morphology. Am J Psychiatry 162:1461-472 CrossRef
  23. Johnson T, Nath A (2010) Neurological complications of immune reconstitution in HIV-infected populations. Ann N Y Acad Sci 1184:106-20 CrossRef
  24. Koletar SL, Williams PL, Wu J, McCutchan JA, Cohn SE, Murphy RL, Lederman HM, Currier JS (2004) Long-term follow-up of HIV-infected individuals who have significant increases in CD4+ cell counts during antiretroviral therapy. Clin Infect Dis 39:1500-506 CrossRef
  25. Kumar AM, Borodowsky I, Fernandez B, Gonzalez L, Kumar M (2007) Human immunodeficiency virus type 1 RNA levels in different regions of human brain: quantification using real-time reverse transcriptase-polymerase chain reaction. J Neurovirol 13:210-24 CrossRef
  26. Maes F, Collignon A, Vandermeulen D, Marchal G, Suetens P (1997) Multimodality image registration by maximization of mutual information. IEEE Trans Med Imaging 16:187-98 CrossRef
  27. McArthur JC, Steiner J, Sacktor N, Nath A (2010) Human immunodeficiency virus-associated neurocognitive disorders: mind the gap. Ann Neurol 67:699-14
  28. McCutchan JA, Wu JW, Robertson K, Koletar SL, Ellis RJ, Cohn S, Taylor M, Woods S, Heaton R, Currier J, Williams PL (2007) HIV suppression by HAART preserves cognitive function in advanced, immune-reconstituted AIDS patients. AIDS 21:1109-117 CrossRef
  29. Meltzer CC, Wells SW, Becher MW, Flanigan KM, Oyler GA, Lee RR (1998) AIDS-related MR hyperintensity of the basal ganglia. AJNR Am J Neuroradiol 19:83-9
  30. Moore DM, Harris R, Lima V, Hogg B, May M, Yip B, Justice A, Mocroft A, Reiss P, Lampe F, Chene G, Costagliola D, Elzi L, Mugavero MJ, Monforte AD, Sabin C, Podzamczer D, Fatkenheuer G, Staszewski S, Gill J, Sterne JA (2009) Effect of baseline CD4 cell counts on the clinical significance of short-term immunologic response to antiretroviral therapy in individuals with virologic suppression. J Acquir Immune Defic Syndr 52:357-63 CrossRef
  31. Murdoch DM, Venter WD, Van Rie A, Feldman C (2007) Immune reconstitution inflammatory syndrome (IRIS): review of common infectious manifestations and treatment options. AIDS Res Ther 4:9 CrossRef
  32. Palella FJ Jr, Deloria-Knoll M, Chmiel JS, Moorman AC, Wood KC, Greenberg AE, Holmberg SD (2003) Survival benefit of initiating antiretroviral therapy in HIV-infected persons in different CD4+ cell strata. Ann Intern Med 138:620-26 CrossRef
  33. Schechter M, Tuboi SH (2006) Discordant immunological and virological responses to antiretroviral therapy. J Antimicrob Chemother 58:506-10 CrossRef
  34. Sidhu N, McCutchan JA (2010) Unmasking of PML by HAART: unusual clinical features and the role of IRIS. J Neuroimmunol 219:100-04 CrossRef
  35. Sled JG, Zijdenbos AP, Evans AC (1998) A nonparametric method for automatic correction of intensity nonuniformity in MRI data. IEEE Trans Med Imaging 17:87-7 CrossRef
  36. Spilt A, Goekoop R, Westendorp RG, Blauw GJ, de Craen AJ, van Buchem MA (2006) Not all age-related white matter hyperintensities are the same: a magnetization transfer imaging study. AJNR Am J Neuroradiol 27:1964-968
  37. Stout JC, Ellis RJ, Jernigan TL, Archibald SL, Abramson I, Wolfson T, McCutchan JA, Wallace MR, Atkinson JH, Grant I (1998) Progressive cerebral volume loss in human immunodeficiency virus infection: a longitudinal volumetric magnetic resonance imaging study. HIV Neurobehavioral Research Center Group. Arch Neurol 55:161-68 CrossRef
  38. Tan R, Westfall AO, Willig JH, Mugavero MJ, Saag MS, Kaslow RA, Kempf MC (2008) Clinical outcome of HIV-infected antiretroviral-naive patients with discordant immunologic and virologic responses to highly active antiretroviral therapy. J Acquir Immune Defic Syndr 47:553-58 CrossRef
  39. Wen W, Sachdev PS, Li JJ, Chen X, Anstey KJ (2009) White matter hyperintensities in the forties: their prevalence and topography in an epidemiological sample aged 44-8. Hum Brain Mapp 30:1155-167 CrossRef
  
• 作者单位：Christine Fennema-Notestine (1) (2)
  Ronald J. Ellis (4)
  Sarah L. Archibald (1)
  Terry L. Jernigan (1) (2)
  Scott L. Letendre (3)
  Randy J. Notestine (1)
  Michael J. Taylor (1)
  Rebecca J. Theilmann (2)
  Michelle D. Julaton (1)
  David J. Croteau (4)
  Tanya Wolfson (6)
  Robert K. Heaton (1)
  Anthony C. Gamst (5)
  Donald R. Franklin Jr. (1)
  David B. Clifford (7)
  Ann C. Collier (8)
  Benjamin B. Gelman (10)
  Christina Marra (8) (9)
  Justin C. McArthur (11)
  J. Allen McCutchan (3)
  Susan Morgello (12) (13)
  David M. Simpson (13)
  Igor Grant (1)
  
  1. Department of Psychiatry, University of California, San Diego, 9500 Gilman Drive #0738, La Jolla, CA, 92093-0738, USA
  2. Department of Radiology, University of California, San Diego, La Jolla, CA, USA
  4. Department of Neurosciences, University of California, San Diego, La Jolla, CA, USA
  3. Department of Medicine, University of California, San Diego, La Jolla, CA, USA
  6. Computational and Applied Statistics Laboratory (CASL), at the San Diego Supercomputer Center (SDSC), La Jolla, CA, USA
  5. Biostatistics and Bioinformatics, University of California, San Diego, La Jolla, CA, USA
  7. Department of Neurology, Washington University in St. Louis, St. Louis, MO, USA
  8. Department of Medicine, University of Washington, Seattle, WA, USA
  10. Department of Pathology, University of Texas Medical Branch, Galveston, TX, USA
  9. Department of Neurology, University of Washington, Seattle, WA, USA
  11. Department of Neurology, Johns Hopkins University, Baltimore, MD, USA
  12. Department of Neuroscience, Mount Sinai School of Medicine, New York, NY, USA
  13. Department of Neurology, Mount Sinai School of Medicine, New York, NY, USA
  
• ISSN：1538-2443

文摘

MRI alterations in the cerebral white (WM) and gray matter (GM) are common in HIV infection, even during successful combination antiretroviral therapy (CART), and their pathophysiology and clinical significance are unclear. We evaluated the association of these alterations with recovery of CD4+ T cells. Seventy-five HIV-infected (HIV+) volunteers in the CNS HIV Anti-Retroviral Therapy Effects Research study underwent brain MRI at two visits. Multi-channel morphometry yielded volumes of total cerebral WM, abnormal WM, cortical and subcortical GM, and ventricular and sulcal CSF. Multivariable linear regressions were used to predict volumetric changes with change in current CD4 and detectable HIV RNA. On average, the cohort (79?% initially on CART) demonstrated loss of total cerebral WM alongside increases in abnormal WM and ventricular volumes. A greater extent of CD4 recovery was associated with increases in abnormal WM and subcortical GM volumes. Virologic suppression was associated with increased subcortical GM volume, independent of CD4 recovery. These findings suggest a possible link between brain alterations and immune recovery, distinct from the influence of virologic suppression. The association of increasing abnormal WM and subcortical GM volumes with CD4+ T cell recovery suggests that neuroinflammation may be one mechanism in CNS pathogenesis.