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01.06.2013

Progressive cerebral injury in the setting of chronic HIV infection and antiretroviral therapy

verfasst von: Assawin Gongvatana, Jaroslaw Harezlak, Steven Buchthal, Eric Daar, Giovanni Schifitto, Thomas Campbell, Michael Taylor, Elyse Singer, Jeffrey Algers, Jianhui Zhong, Mark Brown, Deborah McMahon, Yuen T. So, Deming Mi, Robert Heaton, Kevin Robertson, Constantin Yiannoutsos, Ronald A. Cohen, Bradford Navia, HIV Neuroimaging Consortium

Erschienen in: Journal of NeuroVirology | Ausgabe 3/2013

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Abstract

Emerging evidence suggests that CNS injury and neurocognitive impairment persist in the setting of chronic HIV infection and combination antiretroviral therapy (CART). Yet, whether neurological injury can progress in this setting remains uncertain. Magnetic resonance spectroscopy and neurocognitive and clinical assessments were performed over 2 years in 226 HIV-infected individuals on stable CART, including 138 individuals who were neurocognitively asymptomatic (NA). Concentrations of N-acetylaspartate (NAA), creatine (Cr), choline (Cho), myoinositol, and glutamate/glutamine (Glx) were measured in the midfrontal cortex (MFC), frontal white matter (FWM), and basal ganglia (BG). Longitudinal changes in metabolite levels were determined using linear mixed effect models, as were metabolite changes in relation to global neurocognitive function. HIV-infected subjects showed significant annual decreases in brain metabolite levels in all regions examined, including NAA (2.95 %) and Cho (2.61 %) in the FWM; NAA (1.89 %), Cr (1.84 %), Cho (2.19 %), and Glx (6.05 %) in the MFC; and Glx (2.80 %) in the BG. Similar metabolite decreases were observed in the NA and subclinically impaired subgroups, including subjects with virologic suppression in plasma and CSF. Neurocognitive decline was associated with longitudinal decreases in Glx in the FWM and the BG, and in NAA in the BG. Widespread progressive changes in the brain, including neuronal injury, occur in chronically HIV-infected persons despite stable antiretroviral treatment and virologic suppression and can lead to neurocognitive declines. The basis for these findings is poorly understood and warrants further study.

Antinori A, Arendt G, Becker JT, Brew BJ, Byrd DA, Cherner M, Clifford DB, Cinque P, Epstein LG, Goodkin K, Gisslen M, Grant I, Heaton RK, Joseph J, Marder K, Marra CM, McArthur JC, Nunn M, Price RW, Pulliam L, Robertson KR, Sacktor N, Valcour V, Wojna VE (2007) Updated research nosology for HIV-associated neurocognitive disorders. Neurology 69:1789–1799PubMedCrossRef

Brew BJ, Rosenblum M, Cronin K, Price RW (1995) AIDS dementia complex and HIV-1 brain infection: clinical-virological correlations. Ann Neurol 38:563–570PubMedCrossRef

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 15:324–333PubMedCrossRef

Carey CL, Woods SP, Gonzalez R, Conover E, Marcotte TD, Grant I, Heaton RK (2004) Predictive validity of global deficit scores in detecting neuropsychological impairment in HIV infection. J Clin Exp Neuropsychol 26:307–319PubMedCrossRef

Chang L, Lee PL, Yiannoutsos CT, Ernst T, Marra CM, Richards T, Kolson D, Schifitto G, Jarvik JG, Miller EN, Lenkinski R, Gonzalez G, Navia BA (2004) A multicenter in vivo proton-MRS study of HIV-associated dementia and its relationship to age. NeuroImage 23:1336–1347PubMedCrossRef

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 16:435–444PubMed

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 16:25–32PubMedCrossRef

Ellis RJ, Hsia K, Spector SA, Nelson JA, Heaton RK, Wallace MR, Abramson I, Atkinson JH, Grant I, McCutchan JA (1997) Cerebrospinal fluid human immunodeficiency virus type 1 RNA levels are elevated in neurocognitively impaired individuals with acquired immunodeficiency syndrome. HIV Neurobehavioral Research Center Group. Ann Neurol 42:679–688PubMedCrossRef

Ernst T, Kreis R, Ross BD (1993) Absolute quantitation of water and metabolites in the human brain. I. Compartments and water. J Magn Reson Ser B 102:1–8CrossRef

Hammer SM, Saag MS, Schechter M, Montaner JS, Schooley RT, Jacobsen DM, Thompson MA, Carpenter CC, Fischl MA, Gazzard BG, Gatell JM, Hirsch MS, Katzenstein DA, Richman DD, Vella S, Yeni PG, Volberding PA (2006) Treatment for adult HIV infection: 2006 recommendations of the International AIDS Society-USA panel. JAMA 296:827–843PubMedCrossRef

Harezlak J, Buchthal S, Taylor M, Schifitto G, Zhong J, Daar E, Alger J, Singer E, Campbell T, Yiannoutsos C, Cohen R, Navia B (2011) Persistence of HIV-associated cognitive impairment, inflammation, and neuronal injury in era of highly active antiretroviral treatment. AIDS 25:625–633PubMedCrossRef

Heaton RK, Clifford DB, Franklin DR Jr, Woods SP, Ake C, Vaida F, Ellis RJ, Letendre SL, Marcotte TD, Atkinson JH, Rivera-Mindt M, Vigil OR, Taylor MJ, Collier AC, Marra CM, Gelman BB, McArthur JC, Morgello S, Simpson DM, McCutchan JA, Abramson I, Gamst A, Fennema-Notestine C, Jernigan TL, Wong J, Grant I (2010) HIV-associated neurocognitive disorders persist in the era of potent antiretroviral therapy: CHARTER Study. Neurology 75:2087–2096PubMedCrossRef

Heaton RK, Franklin DR, Ellis RJ, McCutchan JA, Letendre SL, Leblanc S, Corkran SH, Duarte NA, Clifford DB, Woods SP, Collier AC, Marra CM, Morgello S, Mindt MR, Taylor MJ, Marcotte TD, Atkinson JH, Wolfson T, Gelman BB, McArthur JC, Simpson DM, Abramson I, Gamst A, Fennema-Notestine C, Jernigan TL, Wong J, Grant I (2011) HIV-associated neurocognitive disorders before and during the era of combination antiretroviral therapy: differences in rates, nature, and predictors. J Neurovirol 17:3–16PubMedCrossRef

Heaton RK, Grant I, Butters N, White DA, Kirson D, Atkinson JH, McCutchan JA, Taylor MJ, Kelly MD, Ellis RJ et al (1995) The HNRC 500–neuropsychology of HIV infection at different disease stages. HIV Neurobehavioral Research Center. J Int Neuropsychol Soc 1:231–251PubMedCrossRef

Kantarci K, Weigand SD, Petersen RC, Boeve BF, Knopman DS, Gunter J, Reyes D, Shiung M, O’Brien PC, Smith GE, Ivnik RJ, Tangalos EG, Jack CR Jr (2007) Longitudinal 1H MRS changes in mild cognitive impairment and Alzheimer’s disease. Neurobiol Aging 28:1330–1339PubMedCrossRef

Kreis R, Ernst T, Ross BD (1993) Absolute quantitation of water and metabolites in the human brain. II. Metabolite concentrations. J Magn Reson Ser B 102:9–19CrossRef

Laird NM, Ware JH (1982) Random-effects models for longitudinal data. Biometrics 38:963–974PubMedCrossRef

Lee PL, Yiannoutsos CT, Ernst T, Chang L, Marra CM, Jarvik JG, Richards TL, Kwok EW, Kolson DL, Simpson D, Tang CY, Schifitto G, Ketonen LM, Meyerhoff DJ, Lenkinski RE, Gonzalez RG, Navia BA (2003) A multi-center 1H MRS study of the AIDS dementia complex: validation and preliminary analysis. J Magn Reson Imaging 17:625–633PubMedCrossRef

Lentz MR, Kim WK, Lee V, Bazner S, Halpern EF, Venna N, Williams K, Rosenberg ES, Gonzalez RG (2009) Changes in MRS neuronal markers and T cell phenotypes observed during early HIV infection. Neurology 72:1465–1472PubMedCrossRef

Letendre SL, Zheng JC, Kaul M, Yiannoutsos CT, Ellis RJ, Taylor MJ, Marquie-Beck J, Navia B (2011) Chemokines in cerebrospinal fluid correlate with cerebral metabolite patterns in HIV-infected individuals. J Neurovirol 17:63–69PubMedCrossRef

Lopez-Villegas D, Lenkinski RE, Frank I (1997) Biochemical changes in the frontal lobe of HIV-infected individuals detected by magnetic resonance spectroscopy. Proc Natl Acad Sci USA 94:9854–9859PubMedCrossRef

McArthur JC, McClernon DR, Cronin MF, Nance-Sproson TE, Saah AJ, St Clair M, Lanier ER (1997) Relationship between human immunodeficiency virus-associated dementia and viral load in cerebrospinal fluid and brain. Ann Neurol 42:689–698PubMedCrossRef

Meyerhoff DJ, Bloomer C, Cardenas V, Norman D, Weiner MW, Fein G (1999) Elevated subcortical choline metabolites in cognitively and clinically asymptomatic HIV+ patients. Neurology 52:995–1003PubMedCrossRef

Mohamed MA, Barker PB, Skolasky RL, Selnes OA, Moxley RT, Pomper MG, Sacktor NC (2010) Brain metabolism and cognitive impairment in HIV infection: a 3-T magnetic resonance spectroscopy study. Magn Reson Imaging 28:1251–1257PubMedCrossRef

Navia BA, Cho ES, Petito CK, Price RW (1986a) The AIDS dementia complex: II. Neuropathology. Ann Neurol 19:525–535PubMedCrossRef

Navia BA, Jordan BD, Price RW (1986b) The AIDS dementia complex: I. Clinical features. Ann Neurol 19:517–524PubMedCrossRef

Olson BL, Holshouser BA, Britt W 3rd, Mueller C, Baqai W, Patra S, Petersen F, Kirsch WM (2008) Longitudinal metabolic and cognitive changes in mild cognitive impairment patients. Alzheimer Dis Assoc Disord 22:269–277PubMedCrossRef

Palella FJ Jr, Delaney KM, Moorman AC, Loveless MO, Fuhrer J, Satten GA, Aschman DJ, Holmberg SD (1998) Declining morbidity and mortality among patients with advanced human immunodeficiency virus infection. HIV Outpatient Study Investigators. N Engl J Med 338:853–860PubMedCrossRef

Paul RH, Yiannoutsos CT, Miller EN, Chang L, Marra CM, Schifitto G, Ernst T, Singer E, Richards T, Jarvik GJ, Price R, Meyerhoff DJ, Kolson D, Ellis RJ, Gonzalez G, Lenkinski RE, Cohen RA, Navia BA (2007) Proton MRS and neuropsychological correlates in AIDS dementia complex: evidence of subcortical specificity. J Neuropsychiatry Clin Neurosci 19:283–292PubMedCrossRef

Pilatus U, Lais C, Rochmont Adu M, Kratzsch T, Frolich L, Maurer K, Zanella FE, Lanfermann H, Pantel J (2009) Conversion to dementia in mild cognitive impairment is associated with decline of N-actylaspartate and creatine as revealed by magnetic resonance spectroscopy. Psychiatry Res 173:1–7PubMedCrossRef

Provencher SW (2001) Automatic quantitation of localized in vivo 1H spectra with LCModel. NMR Biomed 14:260–264PubMedCrossRef

Rippeth JD, Heaton RK, Carey CL, Marcotte TD, Moore DJ, Gonzalez R, Wolfson T, Grant I (2004) Methamphetamine dependence increases risk of neuropsychological impairment in HIV infected persons. J Int Neuropsychol Soc: JINS 10:1–14PubMed

Robertson KR, Smurzynski M, Parsons TD, Wu K, Bosch RJ, Wu J, McArthur JC, Collier AC, Evans SR, Ellis RJ (2007) The prevalence and incidence of neurocognitive impairment in the HAART era. AIDS 21:1915–1921PubMedCrossRef

Rostasy K, Monti L, Yiannoutsos C, Kneissl M, Bell J, Kemper TL, Hedreen JC, Navia BA (1999) Human immunodeficiency virus infection, inducible nitric oxide synthase expression, and microglial activation: pathogenetic relationship to the acquired immunodeficiency syndrome dementia complex. Ann Neurol 46:207–216PubMedCrossRef

Sacktor N, McDermott MP, Marder K, Schifitto G, Selnes OA, McArthur JC, Stern Y, Albert S, Palumbo D, Kieburtz K, De Marcaida JA, Cohen B, Epstein L (2002) HIV-associated cognitive impairment before and after the advent of combination therapy. J Neurovirol 8:136–142PubMedCrossRef

Schott JM, Frost C, MacManus DG, Ibrahim F, Waldman AD, Fox NC (2010) Short echo time proton magnetic resonance spectroscopy in Alzheimer’s disease: a longitudinal multiple time point study. Brain 133:3315–3322PubMedCrossRef

Thompson PM, Dutton RA, Hayashi KM, Toga AW, Lopez OL, Aizenstein HJ, Becker JT (2005) Thinning of the cerebral cortex visualized in HIV/AIDS reflects CD4+ T lymphocyte decline. Proc Natl Acad Sci U S A 102:15647–15652PubMedCrossRef

Tozzi V, Balestra P, Bellagamba R, Corpolongo A, Salvatori MF, Visco-Comandini U, Vlassi C, Giulianelli M, Galgani S, Antinori A, Narciso P (2007) Persistence of neuropsychologic deficits despite long-term highly active antiretroviral therapy in patients with HIV-related neurocognitive impairment: prevalence and risk factors. J Acquir Immune Defic Syndr 45:174–182PubMedCrossRef

Tracey I, Carr CA, Guimaraes AR, Worth JL, Navia BA, Gonzalez RG (1996) Brain choline-containing compounds are elevated in HIV-positive patients before the onset of AIDS dementia complex: a proton magnetic resonance spectroscopic study. Neurology 46:783–788PubMedCrossRef

Tracey I, Lane J, Chang I, Navia B, Lackner A, Gonzalez RG (1997) 1H magnetic resonance spectroscopy reveals neuronal injury in a simian immunodeficiency virus macaque model. J Acquir Immune Defic Syndr Hum Retrovirol 15:21–27PubMedCrossRef

Urenjak J, Williams SR, Gadian DG, Noble M (1993) Proton nuclear magnetic resonance spectroscopy unambiguously identifies different neural cell types. J Neurosci 13:981–989PubMed

Valcour V, Shikuma C, Shiramizu B, Watters M, Poff P, Selnes O, Holck P, Grove J, Sacktor N (2004) Higher frequency of dementia in older HIV-1 individuals: the Hawaii Aging with HIV-1 Cohort. Neurology 63:822–827PubMedCrossRef

Valcour VG, Shikuma CM, Shiramizu BT, Williams AE, Watters MR, Poff PW, Grove JS, Selnes OA, Sacktor NC (2005) Diabetes, insulin resistance, and dementia among HIV-1-infected patients. J Acquir Immune Defic Syndr 38:31–36PubMedCrossRef

van Gorp WG, Hinkin CH (2005) Triple trouble: cognitive deficits from hepatitis C, HIV, and methamphetamine. Neurology 64:1328–1329PubMedCrossRef

Yiannoutsos CT, Ernst T, Chang L, Lee PL, Richards T, Marra CM, Meyerhoff DJ, Jarvik JG, Kolson D, Schifitto G, Ellis RJ, Swindells S, Simpson DM, Miller EN, Gonzalez RG, Navia BA (2004) Regional patterns of brain metabolites in AIDS dementia complex. NeuroImage 23:928–935PubMedCrossRef

Titel: Progressive cerebral injury in the setting of chronic HIV infection and antiretroviral therapy
verfasst von: Assawin Gongvatana
Jaroslaw Harezlak
Steven Buchthal
Eric Daar
Giovanni Schifitto
Thomas Campbell
Michael Taylor
Elyse Singer
Jeffrey Algers
Jianhui Zhong
Mark Brown
Deborah McMahon
Yuen T. So
Deming Mi
Robert Heaton
Kevin Robertson
Constantin Yiannoutsos
Ronald A. Cohen
Bradford Navia
HIV Neuroimaging Consortium
Publikationsdatum: 01.06.2013
Verlag: Springer US
Erschienen in: Journal of NeuroVirology / Ausgabe 3/2013
Print ISSN: 1355-0284
Elektronische ISSN: 1538-2443
DOI: https://doi.org/10.1007/s13365-013-0162-1

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