Top

Current HIV/AIDS Reports

Published in:

01-02-2019 | Human Immunodeficiency Virus | Central Nervous System and Cognition (SS Spudich, Section Editor)

Brain PET Imaging: Value for Understanding the Pathophysiology of HIV-associated Neurocognitive Disorder (HAND)

Authors: Sanhita Sinharay, Dima A. Hammoud

Published in: Current HIV/AIDS Reports | Issue 1/2019

Abstract

Purpose of Review

The purpose of this review is to summarize recent developments in PET imaging of neuropathologies underlying HIV-associated neurocognitive dysfunction (HAND). We concentrate on the recent post antiretroviral era (ART), highlighting clinical and preclinical brain PET imaging studies.

Recent Findings

In the post ART era, PET imaging has been used to better understand perturbations of glucose metabolism, neuroinflammation, the function of neurotransmitter systems, and amyloid/tau protein deposition in the brains of HIV-infected patients and HIV animal models. Preclinical and translational findings from those studies shed a new light on the complex pathophysiology underlying HAND.

Summary

The molecular imaging capabilities of PET in neuro-HIV are great complements for structural imaging modalities. Recent and future PET imaging studies can improve our understanding of neuro-HIV and provide biomarkers of disease progress that could be used as surrogate endpoints in the evaluation of the effectiveness of potential neuroprotective therapies.

McArthur JC, Steiner J, Sacktor N, Nath A. Human immunodeficiency virus-associated neurocognitive disorders: mind the gap. Ann Neurol. 2010;67(6):699–714.PubMed

Heaton RK, Franklin DR, Ellis RJ, McCutchan JA, Letendre SL, Leblanc S, et al. HIV-associated neurocognitive disorders before and during the era of combination antiretroviral therapy: differences in rates, nature, and predictors. J Neurovirol. 2011;17(1):3–16. https://doi.org/10.1007/s13365-010-0006-1.PubMedCrossRef

Gates TM, Cysique LA. The chronicity of HIV infection should drive the research strategy of NeuroHIV treatment studies: a critical review. CNS Drugs. 2016;30(1):53–69. https://doi.org/10.1007/s40263-015-0302-7.PubMedPubMedCentralCrossRef

Brew BJ. Evidence for a change in AIDS dementia complex in the era of highly active antiretroviral therapy and the possibility of new forms of AIDS dementia complex. AIDS (London, England). 2004;18(Suppl 1):S75–8.CrossRef

Pence BW, Mills JC, Bengtson AM, Gaynes BN, Breger TL, Cook RL, et al. Association of increased chronicity of depression with HIV appointment attendance, treatment failure, and mortality among HIV-infected adults in the United States. JAMA Psychiatry. 2018;75:379–85. https://doi.org/10.1001/jamapsychiatry.2017.4726.PubMedPubMedCentralCrossRef

Spudich SS, Ances BM. CROI 2017: neurologic complications of HIV infection. Top Antivir Med. 2017;25(2):69–76.PubMedPubMedCentral

Farhadian S, Patel P, Spudich S. Neurological complications of HIV infection. Curr Infect Dis Rep. 2017;19(12):50. https://doi.org/10.1007/s11908-017-0606-5.PubMedCrossRef

Keegan MR, Chittiprol S, Letendre SL, Winston A, Fuchs D, Boasso A, et al. Tryptophan metabolism and its relationship with depression and cognitive impairment among HIV-infected individuals. Int J Tryptophan Res. 2016;9:79–88. https://doi.org/10.4137/ijtr.s36464.PubMedPubMedCentralCrossRef

Sperner-Unterweger B, Kohl C, Fuchs D. Immune changes and neurotransmitters: possible interactions in depression? Prog Neuro-Psychopharmacol Biol Psychiatry. 2014;48:268–76. https://doi.org/10.1016/j.pnpbp.2012.10.006.CrossRef

10.

Hammoud DA, Endres CJ, Hammond E, Uzuner O, Brown A, Nath A, et al. Imaging serotonergic transmission with [11C]DASB-PET in depressed and non-depressed patients infected with HIV. NeuroImage. 2010;49(3):2588–95. https://doi.org/10.1016/j.neuroimage.2009.10.037.PubMedCrossRef

11.

Chang L, Wang GJ, Volkow ND, Ernst T, Telang F, Logan J, et al. Decreased brain dopamine transporters are related to cognitive deficits in HIV patients with or without cocaine abuse. NeuroImage. 2008;42(2):869–78.PubMedPubMedCentralCrossRef

12.

Nagano-Saito A, Liu J, Doyon J, Dagher A. Dopamine modulates default mode network deactivation in elderly individuals during the tower of London task. Neurosci Lett. 2009;458(1):1–5.PubMedCrossRef

13.

Haynes BI, Pitkanen M, Kulasegaram R, Casey SJ, Schutte M, Towgood K, et al. HIV: ageing, cognition and neuroimaging at 4-year follow-up. HIV Med. 2018;19:376–85. https://doi.org/10.1111/hiv.12598.PubMedCrossRef

14.

Wright PW, Vaida FF, Fernandez RJ, Rutlin J, Price RW, Lee E, et al. Cerebral white matter integrity during primary HIV infection. AIDS (London, England). 2015;29(4):433–42. https://doi.org/10.1097/qad.0000000000000560.CrossRef

15.

Ragin AB, Du H, Ochs R, Wu Y, Sammet CL, Shoukry A, et al. Structural brain alterations can be detected early in HIV infection. Neurology. 2012;79(24):2328–34. https://doi.org/10.1212/WNL.0b013e318278b5b4.PubMedPubMedCentralCrossRef

16.

Correa DG, Zimmermann N, Ventura N, Tukamoto G, Doring T, Leite SC, et al. Longitudinal evaluation of resting-state connectivity, white matter integrity and cortical thickness in stable HIV infection: preliminary results. Neuroradiol J. 2017;30(6):535–45. https://doi.org/10.1177/1971400917739273.PubMedPubMedCentralCrossRef

17.

Guha A, Brier MR, Ortega M, Westerhaus E, Nelson B, Ances BM. Topographies of cortical and subcortical volume loss in HIV and aging in the cART era. J Acquir Immune Defic Syndr. 2016;73(4):374–83. https://doi.org/10.1097/qai.0000000000001111.PubMedPubMedCentralCrossRef

18.

Descamps M, Hyare H, Stebbing J, Winston A. Magnetic resonance imaging and spectroscopy of the brain in HIV disease. J HIV Ther. 2008;13(3):55–8.PubMed

19.

Cysique LA, Moffat K, Moore DM, Lane TA, Davies NW, Carr A, et al. HIV, vascular and aging injuries in the brain of clinically stable HIV-infected adults: a (1)H MRS study. PLoS One. 2013;8(4):e61738. https://doi.org/10.1371/journal.pone.0061738.PubMedPubMedCentralCrossRef

20.

Hammoud DA, Sinharay S, Steinbach S, Wakim PG, Geannopolous K, Traino K, et al. Global and regional brain hypometabolism on FDG-PET in treated HIV-infected individuals. Neurology. 2018;91(17):e1591-e601. https://doi.org/10.1212/wnl.0000000000006398.

21.

Towgood KJ, Pitkanen M, Kulasegaram R, Fradera A, Soni S, Sibtain N, et al. Regional cerebral blood flow and FDG uptake in asymptomatic HIV-1 men. Hum Brain Mapp. 2013;34(10):2484–93. https://doi.org/10.1002/hbm.22078.PubMedCrossRef

22.

Andersen AB, Law I, Krabbe KS, Bruunsgaard H, Ostrowski SR, Ullum H, et al. Cerebral FDG-PET scanning abnormalities in optimally treated HIV patients. J Neuroinflammation. 2010;7:13. https://doi.org/10.1186/1742-2094-7-13.PubMedPubMedCentralCrossRef

23.

Vera JH, Guo Q, Cole JH, Boasso A, Greathead L, Kelleher P, et al. Neuroinflammation in treated HIV-positive individuals: a TSPO PET study. Neurology. 2016;86(15):1425–32. https://doi.org/10.1212/wnl.0000000000002485.PubMedPubMedCentralCrossRef

24.

Coughlin JM, Wang Y, Ma S, Yue C, Kim PK, Adams AV, et al. Regional brain distribution of translocator protein using [(11)C]DPA-713 PET in individuals infected with HIV. J Neurovirol. 2014;20(3):219–32. https://doi.org/10.1007/s13365-014-0239-5.PubMedPubMedCentralCrossRef

25.

Garvey LJ, Pavese N, Politis M, Ramlackhansingh A, Brooks DJ, Taylor-Robinson SD, et al. Increased microglia activation in neurologically asymptomatic HIV-infected patients receiving effective ART. AIDS (London, England). 2014;28(1):67–72. https://doi.org/10.1097/01.aids.0000432467.54003.f7.CrossRef

26.

Wiley CA, Lopresti BJ, Becker JT, Boada F, Lopez OL, Mellors J, et al. Positron emission tomography imaging of peripheral benzodiazepine receptor binding in human immunodeficiency virus-infected subjects with and without cognitive impairment. J Neurovirol. 2006;12(4):262–71.PubMedCrossRef

27.

Hammoud DA, Endres CJ, Chander AR, Guilarte TR, Wong DF, Sacktor NC, et al. Imaging glial cell activation with [11C]-R-PK11195 in patients with AIDS. J Neurovirol. 2005;11(4):346–55.PubMedCrossRef

28.

Wang GJ, Chang L, Volkow ND, Telang F, Logan J, Ernst T, et al. Decreased brain dopaminergic transporters in HIV-associated dementia patients. Brain. 2004;127(Pt 11):2452–8.PubMedCrossRef

29.

Ances BM, Christensen JJ, Teshome M, Taylor J, Xiong C, Aldea P, et al. Cognitively unimpaired HIV-positive subjects do not have increased 11C-PiB: a case-control study. Neurology. 2010;75(2):111–5. https://doi.org/10.1212/WNL.0b013e3181e7b66e.PubMedPubMedCentralCrossRef

30.

Ances BM, Benzinger TL, Christensen JJ, Thomas J, Venkat R, Teshome M, et al. 11C-PiB imaging of human immunodeficiency virus-associated neurocognitive disorder. Arch Neurol. 2012;69(1):72–7. https://doi.org/10.1001/archneurol.2011.761.PubMedPubMedCentralCrossRef

31.

Turner RS, Chadwick M, Horton WA, Simon GL, Jiang X, Esposito G. An individual with human immunodeficiency virus, dementia, and central nervous system amyloid deposition. Alzheimers Dement (Amsterdam, Netherlands). 2016;4:1–5. https://doi.org/10.1016/j.dadm.2016.03.009.CrossRef

32.

Tripathi M, Yadav S, Kumar V, Kumar R, Tripathi M, Gaikwad S, et al. HIV encephalitis with subcortical tau deposition: imaging pathology in vivo using F-18 THK 5117. Eur J Nucl Med Mol Imaging. 2016;43(13):2456–7. https://doi.org/10.1007/s00259-016-3473-7.PubMedCrossRef

33.

Beck SE, Queen SE, Metcalf Pate KA, Mangus LM, Abreu CM, Gama L, et al. An SIV/macaque model targeted to study HIV-associated neurocognitive disorders. J Neurovirol. 2018;24(2):204–12. https://doi.org/10.1007/s13365-017-0582-4.PubMedCrossRef

34.

Honeycutt JB, Garcia JV. Humanized mice: models for evaluating neuroHIV and cure strategies. J Neurovirol. 2018;24(2):185–91. https://doi.org/10.1007/s13365-017-0567-3.PubMedCrossRef

35.

Nixon CC, Mavigner M, Silvestri G, Garcia JV. In vivo models of human immunodeficiency virus persistence and cure strategies. J Infect Dis. 2017;215(suppl_3):S142–s51. https://doi.org/10.1093/infdis/jiw637.PubMedPubMedCentralCrossRef

36.

Williams K, Lackner A, Mallard J. Non-human primate models of SIV infection and CNS neuropathology. Curr Opin Virol. 2016;19:92–8. https://doi.org/10.1016/j.coviro.2016.07.012.PubMedPubMedCentralCrossRef

37.

Hatziioannou T, Evans DT. Animal models for HIV/AIDS research. Nat Rev Microbiol. 2012;10(12):852–67. https://doi.org/10.1038/nrmicro2911.PubMedPubMedCentralCrossRef

38.

Reid W, Sadowska M, Denaro F, Rao S, Foulke J, Hayes N, et al. An HIV-1 transgenic rat that develops HIV-related pathology and immunologic dysfunction. Proc Natl Acad Sci. 2001;98(16):9271–6.PubMedCrossRef

39.

Casas R, Muthusamy S, Wakim PG, Sinharay S, Lentz MR, Reid WC, et al. MR brain volumetric measurements are predictive of neurobehavioral impairment in the HIV-1 transgenic rat. NeuroImage Clin. 2018;17:659–66. https://doi.org/10.1016/j.nicl.2017.11.018.PubMedCrossRef

40.

Reid WC, Ibrahim WG, Kim SJ, Denaro F, Casas R, Lee DE, et al. Characterization of neuropathology in the HIV-1 transgenic rat at different ages. J Neuroimmunol. 2016;292:116–25. https://doi.org/10.1016/j.jneuroim.2016.01.022.PubMedPubMedCentralCrossRef

41.

Vigorito M, Connaghan KP, Chang SL. The HIV-1 transgenic rat model of neuroHIV. Brain Behav Immun. 2015;48:336–49. https://doi.org/10.1016/j.bbi.2015.02.020.PubMedPubMedCentralCrossRef

42.

Lee DE, Yue X, Ibrahim WG, Lentz MR, Peterson KL, Jagoda EM, et al. Lack of neuroinflammation in the HIV-1 transgenic rat: an [(18)F]-DPA714 PET imaging study. J Neuroinflammation. 2015;12(1):171. https://doi.org/10.1186/s12974-015-0390-9.PubMedPubMedCentralCrossRef

43.

Lentz MR, Peterson KL, Ibrahim WG, Lee DE, Sarlls J, Lizak MJ, et al. Diffusion tensor and volumetric magnetic resonance measures as biomarkers of brain damage in a small animal model of HIV. PLoS One. 2014;9(8):e105752. https://doi.org/10.1371/journal.pone.0105752.PubMedPubMedCentralCrossRef

44.

Lee DE, Reid WC, Ibrahim WG, Peterson KL, Lentz MR, Maric D, et al. Imaging dopaminergic dysfunction as a surrogate marker of neuropathology in a small-animal model of HIV. Mol Imaging. 2014;13:1–10.PubMed

45.

Ito R, Takahashi T, Katano I, Ito M. Current advances in humanized mouse models. Cell Mol Immunol. 2012;9(3):208–14.PubMedPubMedCentralCrossRef

46.

Kieffer C, Ladinsky MS, Ninh A, Galimidi RP, Bjorkman PJ. Longitudinal imaging of HIV-1 spread in humanized mice with parallel 3D immunofluorescence and electron tomography. elife. 2017;6:e23282. https://doi.org/10.7554/eLife.23282.PubMedPubMedCentralCrossRef

47.

Boska MD, Dash PK, Knibbe J, Epstein AA, Akhter SP, Fields N, et al. Associations between brain microstructures, metabolites, and cognitive deficits during chronic HIV-1 infection of humanized mice. Mol Neurodegener. 2014;9:58. https://doi.org/10.1186/1750-1326-9-58.PubMedPubMedCentralCrossRef

48.

Epstein AA, Narayanasamy P, Dash PK, High R, Bathena SP, Gorantla S, et al. Combinatorial assessments of brain tissue metabolomics and histopathology in rodent models of human immunodeficiency virus infection. J Neuroimmune Pharmacol. 2013;8(5):1224–38. https://doi.org/10.1007/s11481-013-9461-9.PubMedPubMedCentralCrossRef

49.

Dash PK, Gorantla S, Gendelman HE, Knibbe J, Casale GP, Makarov E, et al. Loss of neuronal integrity during progressive HIV-1 infection of humanized mice. J Neurosci. 2011;31(9):3148–57. https://doi.org/10.1523/jneurosci.5473-10.2011.PubMedPubMedCentralCrossRef

50.

Beck SE, Kelly KM, Queen SE, Adams RJ, Zink MC, Tarwater PM, et al. Macaque species susceptibility to simian immunodeficiency virus: increased incidence of SIV central nervous system disease in pigtailed macaques versus rhesus macaques. J Neurovirol. 2015;21(2):148–58. https://doi.org/10.1007/s13365-015-0313-7.PubMedCrossRef

51.

Garcia-Lerma JG, Heneine W. Animal models of antiretroviral prophylaxis for HIV prevention. Curr Opin HIV AIDS. 2012;7(6):505–13. https://doi.org/10.1097/COH.0b013e328358e484.PubMedCrossRef

52.

Schmitz JE, Korioth-Schmitz B. Immunopathogenesis of simian immunodeficiency virus infection in nonhuman primates. Curr Opin HIV AIDS. 2013;8(4):273–9. https://doi.org/10.1097/COH.0b013e328361cf5b.PubMedCrossRef

53.

Sui Y, Gordon S, Franchini G, Berzofsky JA. Nonhuman primate models for HIV/AIDS vaccine development. Curr Protoc Immunol. 2013;102:Unit 12.4. https://doi.org/10.1002/0471142735.im1214s102.CrossRef

54.

Evans DT, Silvestri G. Nonhuman primate models in AIDS research. Curr Opin HIV AIDS. 2013;8(4):255–61. https://doi.org/10.1097/COH.0b013e328361cee8.PubMedPubMedCentralCrossRef

55.

Dang Q, Whitted S, Goeken RM, Brenchley JM, Matsuda K, Brown CR, et al. Development of neurological disease is associated with increased immune activation in simian immunodeficiency virus-infected macaques. J Virol. 2012;86(24):13795–9. https://doi.org/10.1128/jvi.02174-12.PubMedPubMedCentralCrossRef

56.

Matsuda K, Brown CR, Foley B, Goeken R, Whitted S, Dang Q, et al. Laser capture microdissection assessment of virus compartmentalization in the central nervous systems of macaques infected with neurovirulent simian immunodeficiency virus. J Virol. 2013;87(16):8896–908. https://doi.org/10.1128/jvi.00874-13.PubMedPubMedCentralCrossRef

57.

Matsuda K, Dang Q, Brown CR, Keele BF, Wu F, Ourmanov I, et al. Characterization of simian immunodeficiency virus (SIV) that induces SIV encephalitis in rhesus macaques with high frequency: role of TRIM5 and major histocompatibility complex genotypes and early entry to the brain. J Virol. 2014;88(22):13201–11. https://doi.org/10.1128/jvi.01996-14.PubMedPubMedCentralCrossRef

58.

Hsu DC, Sunyakumthorn P, Wegner M, Schuetz A, Silsorn D, Estes JD, et al. Central nervous system inflammation and infection during early, nonaccelerated simian-human immunodeficiency virus infection in rhesus macaques. J Virol. 2018;92(11). https://doi.org/10.1128/jvi.00222-18.

59.

Lee KM, Chiu KB, Renner NA, Sansing HA, Didier PJ, MacLean AG. Form follows function: astrocyte morphology and immune dysfunction in SIV neuroAIDS. J Neurovirol. 2014;20(5):474–84. https://doi.org/10.1007/s13365-014-0267-1.PubMedPubMedCentralCrossRef

60.

Meulendyke KA, Pletnikov MV, Engle EL, Tarwater PM, Graham DR, Zink MC. Early minocycline treatment prevents a decrease in striatal dopamine in an SIV model of HIV-associated neurological disease. J Neuroimmune Pharmacol. 2012;7(2):454–64. https://doi.org/10.1007/s11481-011-9332-1.PubMedCrossRef

61.

Santangelo PJ, Cicala C, Byrareddy SN, Ortiz KT, Little D, Lindsay KE, et al. Early treatment of SIV+ macaques with an alpha4beta7 mAb alters virus distribution and preserves CD4(+) T cells in later stages of infection. Mucosal Immunol. 2018;11(3):932–46. https://doi.org/10.1038/mi.2017.112.PubMedCrossRef

62.

Santangelo PJ, Rogers KA, Zurla C, Blanchard EL, Gumber S, Strait K, et al. Whole-body immunoPET reveals active SIV dynamics in viremic and antiretroviral therapy-treated macaques. Nat Methods. 2015;12(5):427–32. https://doi.org/10.1038/nmeth.3320.PubMedPubMedCentralCrossRef

63.

Freeman ZT, Rice KA, Soto PL, Pate KA, Weed MR, Ator NA, et al. Neurocognitive dysfunction and pharmacological intervention using guanfacine in a rhesus macaque model of self-injurious behavior. Transl Psychiatry. 2015;5:e567. https://doi.org/10.1038/tp.2015.61.PubMedPubMedCentralCrossRef

64.

Venneti S, Lopresti BJ, Wang G, Bissel SJ, Mathis CA, Meltzer CC, et al. PET imaging of brain macrophages using the peripheral benzodiazepine receptor in a macaque model of neuroAIDS. J Clin Invest. 2004;113(7):981–9. https://doi.org/10.1172/jci20227.PubMedPubMedCentralCrossRef

65.

Wallace M, Pyzalski R, Horejsh D, Brown C, Djavani M, Lu Y, et al. Whole body positron emission tomography imaging of activated lymphoid tissues during acute simian-human immunodeficiency virus 89.6PD infection in rhesus macaques. Virology. 2000;274(2):255–61.PubMedCrossRef

66.

Scharko AM, Perlman SB, PWN H, Hanson JM, Uno H, Pauza CD. Whole body positron emission tomography imaging of simian immunodeficiency virus-infected rhesus macaques. Proc Natl Acad Sci U S A. 1996;93(13):6425–30.PubMedPubMedCentralCrossRef

67.

Schreiber-Stainthorp W, Srinivasula S, Sinharay S, Shah S, Wang J, Dodd LE, et al., editors. Brain 18F-FDG PET of SIV-infected macaques after treatment interruption or initiation. Boston: CROI; 2018.

68.

Rottenberg DA, Sidtis JJ, Strother SC, Schaper KA, Anderson JR, Nelson MJ, et al. Abnormal cerebral glucose metabolism in HIV-1 seropositive subjects with and without dementia. J Nucl Med. 1996;37(7):1133–41.PubMed

69.

Hinkin CH, van Gorp WG, Mandelkern MA, Gee M, Satz P, Holston S, et al. Cerebral metabolic change in patients with AIDS: report of a six-month follow-up using positron-emission tomography. J Neuropsychiatry Clin Neurosci. 1995;7(2):180–7. https://doi.org/10.1176/jnp.7.2.180.PubMedCrossRef

70.

von Giesen HJ, Antke C, Hefter H, Wenserski F, Seitz RJ, Arendt G. Potential time course of human immunodeficiency virus type 1-associated minor motor deficits: electrophysiologic and positron emission tomography findings. Arch Neurol. 2000;57(11):1601–7.

71.

van Gorp WG, Mandelkern MA, Gee M, Hinkin CH, Stern CE, Paz DK, et al. Cerebral metabolic dysfunction in AIDS: findings in a sample with and without dementia. J Neuropsychiatry Clin Neurosci. 1992;4(3):280–7. https://doi.org/10.1176/jnp.4.3.280.PubMedCrossRef

72.

Rottenberg DA, Moeller JR, Strother SC, Sidtis JJ, Navia BA, Dhawan V, et al. The metabolic pathology of the AIDS dementia complex. Ann Neurol. 1987;22(6):700–6. https://doi.org/10.1002/ana.410220605.PubMedCrossRef

73.

Rappaport J, Volsky DJ. Role of the macrophage in HIV-associated neurocognitive disorders and other comorbidities in patients on effective antiretroviral treatment. J Neurovirol. 2015;21(3):235–41. https://doi.org/10.1007/s13365-015-0346-y.PubMedPubMedCentralCrossRef

74.

Lipton SA, Gendelman HE. Dementia associated with the acquired immunodeficiency syndrome. N Engl J Med. 1995;332(14):934–40. https://doi.org/10.1056/nejm199504063321407.PubMedCrossRef

75.

Boven LA. Macrophages and HIV-1-associated dementia. Arch Immunol Ther Exp. 2000;48(4):273–9.

76.

Minagar A, Shapshak P, Fujimura R, Ownby R, Heyes M, Eisdorfer C. The role of macrophage/microglia and astrocytes in the pathogenesis of three neurologic disorders: HIV-associated dementia, Alzheimer disease, and multiple sclerosis. J Neurol Sci. 2002;202(1–2):13–23.PubMedCrossRef

77.

Bartels AL, Leenders KL. Neuroinflammation in the pathophysiology of Parkinson’s disease: evidence from animal models to human in vivo studies with [11C]-PK11195 PET. Mov Disord. 2007;22(13):1852–6.PubMedCrossRef

78.

Verma P, Asopa RV. Incidental global hypometabolism in the brain of patient with AIDS-related dementia seen on 18F-Fluorodeoxyglucose positron emission tomography/computed tomography. Indian J Nucl Med. 2018;33(1):73–5. https://doi.org/10.4103/ijnm.IJNM_108_17.PubMedPubMedCentralCrossRef

79.

Tai YF, Pavese N, Gerhard A, Tabrizi SJ, Barker RA, Brooks DJ, et al. Microglial activation in presymptomatic Huntington’s disease gene carriers. Brain. 2007;130(Pt 7):1759–66.PubMedCrossRef

80.

Endres CJ, Pomper MG, James M, Uzuner O, Hammoud DA, Watkins CC, et al. Initial evaluation of 11C-DPA-713, a novel TSPO PET ligand, in humans. J Nucl Med. 2009;50(8):1276–82.PubMedPubMedCentralCrossRef

81.

Chauveau F, Van Camp N, Dolle F, Kuhnast B, Hinnen F, Damont A, et al. Comparative evaluation of the translocator protein radioligands 11C-DPA-713, 18F-DPA-714, and 11C-PK11195 in a rat model of acute neuroinflammation. J Nucl Med. 2009;50(3):468–76.PubMedCrossRef

82.

Brown AK, Fujita M, Fujimura Y, Liow JS, Stabin M, Ryu YH, et al. Radiation dosimetry and biodistribution in monkey and man of 11C-PBR28: a PET radioligand to image inflammation. J Nucl Med. 2007;48(12):2072–9. https://doi.org/10.2967/jnumed.107.044842.PubMedCrossRef

83.

Nath A, Anderson C, Jones M, Maragos W, Booze R, Mactutus C, et al. Neurotoxicity and dysfunction of dopaminergic systems associated with AIDS dementia. J Psychopharmacol (Oxford, England). 2000;14(3):222–7.CrossRef

84.

Marcario JK, Manaye KF, SantaCruz KS, Mouton PR, Berman NE, Cheney PD. Severe subcortical degeneration in macaques infected with neurovirulent simian immunodeficiency virus. J Neurovirol. 2004;10(6):387–99.PubMedCrossRef

85.

Sinharay S, Lee D, Shah S, Muthusamy S, Papadakis GZ, Zhang X, et al. Cross-sectional and longitudinal small animal PET shows pre and post-synaptic striatal dopaminergic deficits in an animal model of HIV. Nucl Med Biol. 2017;55:27–33. https://doi.org/10.1016/j.nucmedbio.2017.08.004.PubMedPubMedCentralCrossRef

86.

Moran LM, Booze RM, Webb KM, Mactutus CF. Neurobehavioral alterations in HIV-1 transgenic rats: evidence for dopaminergic dysfunction. Exp Neurol. 2013;239:139–47. https://doi.org/10.1016/j.expneurol.2012.10.008.PubMedCrossRef

87.

Webb KM, Aksenov MY, Mactutus CF, Booze RM. Evidence for developmental dopaminergic alterations in the human immunodeficiency virus-1 transgenic rat. J Neurovirol. 2010;16(2):168–73. https://doi.org/10.3109/13550281003690177.PubMedPubMedCentralCrossRef

88.

Arseniou S, Arvaniti A, Samakouri M. HIV infection and depression. Psychiatry Clin Neurosci. 2014;68(2):96–109. https://doi.org/10.1111/pcn.12097.PubMedCrossRef

89.

Mills JC, Pence BW, Todd JV, Bengtson AM, Breger TL, Edmonds A, et al. Cumulative burden of depression and all-cause mortality in women living with HIV. Clin Infect Dis. 2018;67:1575–81. https://doi.org/10.1093/cid/ciy264.PubMedCrossRef

90.

Greeson JM, Gettes DR, Spitsin S, Dube B, Benton TD, Lynch KG, et al. The selective serotonin reuptake inhibitor citalopram decreases human immunodeficiency virus receptor and coreceptor expression in immune cells. Biol Psychiatry. 2016;80(1):33–9. https://doi.org/10.1016/j.biopsych.2015.11.003.PubMedCrossRef

91.

Cannon DM, Ichise M, Rollis D, Klaver JM, Gandhi SK, Charney DS, et al. Elevated serotonin transporter binding in major depressive disorder assessed using positron emission tomography and [11C]DASB; comparison with bipolar disorder. Biol Psychiatry. 2007;62(8):870–7.PubMedCrossRef

92.

Bhagwagar Z, Murthy N, Selvaraj S, Hinz R, Taylor M, Fancy S, et al. 5-HTT binding in recovered depressed patients and healthy volunteers: a positron emission tomography study with [11C]DASB. Am J Psychiatry. 2007;164(12):1858–65.PubMedCrossRef

93.

Meyer JH, Houle S, Sagrati S, Carella A, Hussey DF, Ginovart N, et al. Brain serotonin transporter binding potential measured with carbon 11-labeled DASB positron emission tomography: effects of major depressive episodes and severity of dysfunctional attitudes. Arch Gen Psychiatry. 2004;61(12):1271–9.PubMedCrossRef

94.

Shah S, Sinharay S, Lee D, Reid WC, Wakim P, Matsuda K, et al., editors. Longitudinal PET imaging of the serotonergic system in SIV-infected nonhuman primates. Boston: CROI; 2018.

95.

An SF, Giometto B, Groves M, Miller RF, Beckett AA, Gray F, et al. Axonal damage revealed by accumulation of beta-APP in HIV-positive individuals without AIDS. J Neuropathol Exp Neurol. 1997;56(11):1262–8.PubMedCrossRef

96.

Esiri MM, Biddolph SC, Morris CS. Prevalence of Alzheimer plaques in AIDS. J Neurol Neurosurg Psychiatry. 1998;65(1):29–33.PubMedPubMedCentralCrossRef

97.

Anthony IC, Ramage SN, Carnie FW, Simmonds P, Bell JE. Accelerated tau deposition in the brains of individuals infected with human immunodeficiency virus-1 before and after the advent of highly active anti-retroviral therapy. Acta Neuropathol. 2006;111(6):529–38. https://doi.org/10.1007/s00401-006-0037-0.PubMedCrossRef

98.

Green DA, Masliah E, Vinters HV, Beizai P, Moore DJ, Achim CL. Brain deposition of beta-amyloid is a common pathologic feature in HIV positive patients. AIDS (London, England). 2005;19(4):407–11.CrossRef

99.

Soontornniyomkij V, Moore DJ, Gouaux B, Soontornniyomkij B, Tatro ET, Umlauf A, et al. Cerebral beta-amyloid deposition predicts HIV-associated neurocognitive disorders in APOE epsilon4 carriers. AIDS (London, England). 2012;26(18):2327–35. https://doi.org/10.1097/QAD.0b013e32835a117c.CrossRef

100.

Brew BJ, Pemberton L, Blennow K, Wallin A, Hagberg L. CSF amyloid beta42 and tau levels correlate with AIDS dementia complex. Neurology. 2005;65(9):1490–2. https://doi.org/10.1212/01.wnl.0000183293.95787.b7.PubMedCrossRef

101.

Clifford DB, Fagan AM, Holtzman DM, Morris JC, Teshome M, Shah AR, et al. CSF biomarkers of Alzheimer disease in HIV-associated neurologic disease. Neurology. 2009;73(23):1982–7. https://doi.org/10.1212/WNL.0b013e3181c5b445.PubMedPubMedCentralCrossRef

102.

Krut JJ, Zetterberg H, Blennow K, Cinque P, Hagberg L, Price RW, et al. Cerebrospinal fluid Alzheimer’s biomarker profiles in CNS infections. J Neurol. 2013;260(2):620–6. https://doi.org/10.1007/s00415-012-6688-y.PubMedCrossRef

103.

Peluso MJ, Meyerhoff DJ, Price RW, Peterson J, Lee E, Young AC, et al. Cerebrospinal fluid and neuroimaging biomarker abnormalities suggest early neurological injury in a subset of individuals during primary HIV infection. J Infect Dis. 2013;207(11):1703–12. https://doi.org/10.1093/infdis/jit088.PubMedPubMedCentralCrossRef

104.

Steinbrink F, Evers S, Buerke B, Young P, Arendt G, Koutsilieri E, et al. Cognitive impairment in HIV infection is associated with MRI and CSF pattern of neurodegeneration. Eur J Neurol. 2013;20(3):420–8. https://doi.org/10.1111/ene.12006.PubMedCrossRef

105.

Villemagne VL, Dore V, Burnham SC, Masters CL, Rowe CC. Imaging tau and amyloid-beta proteinopathies in Alzheimer disease and other conditions. Nat Rev Neurol. 2018;14(4):225–36. https://doi.org/10.1038/nrneurol.2018.9.PubMedCrossRef

106.

Ortega M, Ances BM. Role of HIV in amyloid metabolism. J Neuroimmune Pharmacol. 2014;9(4):483–91. https://doi.org/10.1007/s11481-014-9546-0.PubMedPubMedCentralCrossRef

107.

Xu J, Ikezu T. The comorbidity of HIV-associated neurocognitive disorders and Alzheimer’s disease: a foreseeable medical challenge in post-HAART era. J Neuroimmune Pharmacol. 2009;4(2):200–12. https://doi.org/10.1007/s11481-008-9136-0.PubMedCrossRef

108.

Rempel HC, Pulliam L. HIV-1 Tat inhibits neprilysin and elevates amyloid beta. AIDS (London, England). 2005;19(2):127–35.CrossRef

109.

Ubhi K, Masliah E. Alzheimer’s disease: recent advances and future perspectives. J Alzheimer's Dis. 2013;33(Suppl 1):S185–94. https://doi.org/10.3233/jad-2012-129028.CrossRef

110.

Stanley LC, Mrak RE, Woody RC, Perrot LJ, Zhang S, Marshak DR, et al. Glial cytokines as neuropathogenic factors in HIV infection: pathogenic similarities to Alzheimer’s disease. J Neuropathol Exp Neurol. 1994;53(3):231–8.PubMedCrossRef

111.

Brown LA, Scarola J, Smith AJ, Sanberg PR, Tan J, Giunta B. The role of tau protein in HIV-associated neurocognitive disorders. Mol Neurodegener. 2014;9:40. https://doi.org/10.1186/1750-1326-9-40.PubMedPubMedCentralCrossRef

112.

Cooley SA, Strain JF, Beaumont H, Boerwinkle AH, Doyle J, Morris JC et al. Tau positron emission tomography binding is not elevated in HIV-Infected individuals. J Infect Dis. 2018. https://doi.org/10.1093/infdis/jiy663.

Title: Brain PET Imaging: Value for Understanding the Pathophysiology of HIV-associated Neurocognitive Disorder (HAND)
Authors: Sanhita Sinharay
Dima A. Hammoud
Publication date: 01-02-2019
Publisher: Springer US
Keywords: Human Immunodeficiency Virus
Positron Emission Tomography
HIV-Associated Dementia
HIV-Associated Dementia
Published in: Current HIV/AIDS Reports / Issue 1/2019
Print ISSN: 1548-3568
Electronic ISSN: 1548-3576
DOI: https://doi.org/10.1007/s11904-019-00419-8

Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Reserve your place

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin

Prof. Florian Limbourg

Prof. Anoop Chauhan

Developed by: Springer Medicine

Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Pediatric Cardiology Video

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

Cardiopulmonary Comorbidity Video

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Valvular Heart Disease Video

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

Watch now

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

16-04-2024 Type 2 Diabetes News

Incentivised to exercise

11-04-2024 Lifestyle Modifications News

New intervention for STEMI-related cardiogenic shock

10-04-2024 Myocardial Infarction News

» View more highlights on the ACC 2024 congress hub page

Image Credits

Illustration of figure on mountain summit/© Orapun / Stock.adobe.com, STEP AAG HeroTeaserCollection image/© Tarek / Generated with AI / Stock.adobe.com, ACC 2024 Pediatric and Congenital Heart Disease: Year in Review/© 2024 American College of Cardiology, ACC 2024 Pulmonary Vascular Disease: Year in Review/© 2024 American College of Cardiology, ACC 2024 Valvular Heart Disease: Year in Review/© 2024 American College of Cardiology, ACC 2024 HF and Cardiomyopathies: Year in Review/© 2024 American College of Cardiology, Woman out walking/© Seventyfour / stock.adobe.com (symbolic image with model), Woman checking smartwatch /© saltdium / stock.adobe.com (symbolic image with model), Cardiac catheterization/© Damian / stock.adobe.com

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Purpose of Review

Recent Findings

Summary

Please log in to get access to this content

Other articles of this Issue 1/2019

The Impact of ACA and Medicaid Expansion on Progress Toward UNAIDS 90-90-90 Goals

Substance Use Screening in HIV Care Settings: a Review and Critique of the Literature

Physiological Changes from Violence-Induced Stress and Trauma Enhance HIV Susceptibility Among Women

HIV, Depression, and Cognitive Impairment in the Era of Effective Antiretroviral Therapy

Medications for Treatment of Opioid Use Disorder among Persons Living with HIV

Social Networks of Substance-Using Populations: Key Issues and Promising New Approaches for HIV

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

Highlights from the ACC 2024 Congress

ACC 2024 Congress Coverage