Positron emission tomography in patients suffering from HIV-1 infection

  • Mike Sathekge
  • Ingeborg Goethals
  • Alex Maes
  • Christophe van de WieleEmail author
Review article


This paper reviews currently available PET studies performed either to improve our understanding of the pathogenesis of HIV-1 infection or to assess the value of PET imaging in the clinical decision making of patients infected with HIV-1 presenting with AIDS-related opportunistic infections and malignancies. FDG PET has shown that HIV-1 infection progresses by distinct anatomical steps, with involvement of the upper torso preceding involvement of the lower part of the torso, and that the degree of FDG uptake relates to viral load. The former finding suggests that lymphoid tissues are engaged in a predictable sequence and that diffusible mediators of activation might be important targets for vaccine or therapeutic intervention strategies. In lipodystrophic HIV-infected patients, limited available data support the hypothesis that stavudine-related lipodystrophy is associated with increased glucose uptake by adipose tissue as a result of the metabolic stress of adipose tissue in response to highly active antiretroviral treatment (HAART). Finally, in early AIDS-related dementia complex (ADC), striatal hypermetabolism is observed, whereas progressive ADC is characterized by a decrease in subcortical and cortical metabolism. In the clinical setting, PET has been shown to allow the differentiation of AIDS-related opportunistic infections and malignancies, and to allow monitoring of side effects of HAART. However, in patients suffering from HIV infection and presenting with extracerebral lymphoma or other human malignancies, knowledge of viraemia is essential when interpreting FDG PET imaging.


HIV infection AIDS PET 


  1. 1.
    Wainberg M, Jeang K. 25 years of HIV-1 research – progress and perspectives. BMC Med 2008;6:31.PubMedCrossRefGoogle Scholar
  2. 2.
    UNAIDS. Epidemiology slides. Joint United Nations Programme on HIV/AIDS. Accessed 26 Mar 2009.
  3. 3.
    Kelleher H, Zaunders J. Decimated or missing in action: CD4+ T cells as targets and effectors in the pathogenesis of primary HIV infection. Curr HIV/AIDS Rep 2006;3:5–12. doi: 10.1007/s11904-006-0002-5.PubMedCrossRefGoogle Scholar
  4. 4.
    Samuel R, Bettiker R, Suh B. AIDS related opportunistic infections, going but not gone. Arch Pharm Res 2002;25:215–28.PubMedCrossRefGoogle Scholar
  5. 5.
    Cadogan M, Dalgleish A. HIV induced AIDS and related cancers: chronic immune activation and future therapeutic strategies. Adv Cancer Res 2008;101:349–95. doi: 10.1016/S0065-230X(08)00409-0.PubMedCrossRefGoogle Scholar
  6. 6.
    Aoki Y, Tosato G. Neoplastic conditions in the context of HIV-1 infection. Curr HIV Res 2004;2:343–9.PubMedCrossRefGoogle Scholar
  7. 7.
    Porter C, Laditka J, Cornman C, Davis D, Logan W. Prevalence of AIDS dementia complex: results from a state-wide population-based registry of Alzheimer's disease and related disorders. J S C Med Assoc 2008;104:223–36.PubMedGoogle Scholar
  8. 8.
    Kramer E, Sanger J. Brain imaging in acquired immunodeficiency syndrome dementia complex. Semin Nucl Med 1990;20:353–63. doi: 10.1016/S0001-2998(05)80239-9.PubMedCrossRefGoogle Scholar
  9. 9.
    Tucker KA, Robertson KR, Lin W, et al. Neuroimaging in human immunodeficiency virus infection. J Neuroimmunol 2004;157:153–16. doi: 10.1016/j.jneuroim.2004.08.036.PubMedCrossRefGoogle Scholar
  10. 10.
    Brunetti A, Berg G, Chiro G, et al. Reversal of brain metabolic abnormalities following treatment of AIDS dementia complex with 3'-azido-2',3'-dideoxythymidine (AZT, zidovudine): a PET-FDG study. J Nucl Med 1989;30:581–90.PubMedGoogle Scholar
  11. 11.
    Bonham S, Meya D, Bohjanen P, Boulware D. Biomarkers of HIV immune reconstitution inflammatory syndrome. Biomark Med 2008;2:349–61. doi: 10.2217/17520363.2.4.349.PubMedCrossRefGoogle Scholar
  12. 12.
    Nath A, Schiess N, Venkatesan A, Rumbaugh J, Sacktor N, McArthur J. Evolution of HIV dementia with HIV infection. Int Rev Psychiatry 2008;20:25–31. doi: 10.1080/09540260701861930.PubMedCrossRefGoogle Scholar
  13. 13.
    Cloyd M, Chen J, Wang I. How does HIV cause AIDS? The homing theory. Mol Med Today 2000;6:108–11. doi: 10.1016/S1357-4310(99)01663-9.PubMedCrossRefGoogle Scholar
  14. 14.
    Lederman M, Margolis L. The lymph node in HIV pathogenesis. Semin Immunol 2008;20:187–95. doi: 10.1016/j.smim.2008.06.001.PubMedCrossRefGoogle Scholar
  15. 15.
    Bakheet S, Powe J. Benign causes of 18-FDG uptake on whole-body imaging. Semin Nucl Med 2000;28:352–8.Google Scholar
  16. 16.
    Brown R, Leung J, Fisher S, Frey K, Ethier S, Wahl R. Intratumoral distribution of tritiated fluorodeoxyglucose in breast carcinoma: are inflammatory cells important? J Nucl Med 1995;36:1854–61.PubMedGoogle Scholar
  17. 17.
    Kubota R, Yamada S, Kubota K, Ishiwata KL, Tamahashi N, Ido T. Intratumoral distribution of fluorine-18-deoxyglucose in vivo: high accumulation in macrophages and granulation tissues studied by microautoradiography. J Nucl Med 1992;33:1972–80.PubMedGoogle Scholar
  18. 18.
    Bental M, Deutsch C. Metabolic changes in activated T cells: an NMR study of human peripheral blood lymphocytes. Magn Reson Med 1993;29:317–26. doi: 10.1002/mrm.1910290307.PubMedCrossRefGoogle Scholar
  19. 19.
    Marjanovic S, Skog S, Heiden T, Tribukait B, Nelson B. Expression of glycolytic isoenzymes in activated human peripheral lymphocytes: cell cycle analysis using flow cytometry. Exp Cell Res 1991;193:425–31. doi: 10.1016/0014-4827(91)90116-C.PubMedCrossRefGoogle Scholar
  20. 20.
    Kwan A, Seltzer M, Czernin J, Chou M, Kao C. Characterization of hilar lymph node by 18F-fluro-2-deoxyglucose positron emission tomography in healthy subjects. Anticancer Res 2001;21:701–6.PubMedGoogle Scholar
  21. 21.
    Scharko A, Perlman S, Hinds P, Hanson J, Uno H, Pauza D. Whole body positron emission tomography imaging of simian immunodeficiency virus-infected rhesus macaques. Proc Natl Acad Sci U S A 1996;93:6425–30. doi: 10.1073/pnas.93.13.6425.PubMedCrossRefGoogle Scholar
  22. 22.
    Wallace M, Pyzalski R, Horejsh D, 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;274:255–61. doi: 10.1006/viro.2000.0479.PubMedCrossRefGoogle Scholar
  23. 23.
    Scharko A, Perlman S, Pyzalski R, Graziano F, Sosman J, Pauza C. Whole-body positron emission tomography in patients with HIV-1 infection. Lancet 2003;20:959–61. doi: 10.1016/S0140-6736(03)14366-8.CrossRefGoogle Scholar
  24. 24.
    Iyengar S, Chin B, Margolick J, Beulah P, Schwartz D. Anatomical loci of HIV-associated immune activation and association with viraemia. Lancet 2003;20:945–50. doi: 10.1016/S0140-6736(03)14363-2.CrossRefGoogle Scholar
  25. 25.
    Brust D, Polis M, Davey R, et al. Fluorodeoxyglucose imaging in healthy subjects with HIV infection: impact of disease stage and therapy on pattern of nodal activation. AIDS 2006;20:495–503.PubMedCrossRefGoogle Scholar
  26. 26.
    Lucignani G, Orunesu E, Cesari M, et al. FDG-PET imaging in HIV-infected subjects: relation with therapy and immunovirological variables. Eur J Nucl Med Mol Imaging 2009;36:640–7. doi: 10.1007/s00259-008-1023-7.PubMedCrossRefGoogle Scholar
  27. 27.
    Goshen E, Davidson T, Avigdor A, Zwas T, Levy I. PET/CT in the evaluation of lymphoma in patients with HIV-1 with suppressed viral loads. Clin Nucl Med 2008;33:610–4. doi: 10.1097/RLU.0b013e3181813047.PubMedCrossRefGoogle Scholar
  28. 28.
    Just PA, Fieschi C, Baillet G, Galicier L, Oksenhendler E, Moretti JL. 18F-fluorodeoxyglucose positron emission tomography/computed tomography in AIDS-related Burkitt lymphoma. AIDS Patient Care STDS 2008;22:695–700. doi: 10.1089/apc.2008.0174.PubMedCrossRefGoogle Scholar
  29. 29.
    Carr A, Samaras K, Thorisdottir A, et al. Diagnosis, prediction, and natural course of HIV-1 protease-inhibitor-associated lipodystrophy, hyperlipidaemia, and diabetes mellitus: a cohort study. Lancet 1999;353:2093–9. doi: 10.1016/S0140-6736(98)08468-2.PubMedCrossRefGoogle Scholar
  30. 30.
    Behrens G, Stoll M, Schmidt R. Lipodystrophy syndrome in HIV infection: what is it, what causes it and how can it be managed? Drug Saf 2000;23:57–76. doi: 10.2165/00002018-200023010-00004.PubMedCrossRefGoogle Scholar
  31. 31.
    Behrens G, Boerner A, Weber K, et al. Impaired glucose phosphorylation and transport in skeletal muscle cause insulin resistance in HIV-1-infected patients with lipodystrophy. J Clin Invest 2002;110:1319–27.PubMedGoogle Scholar
  32. 32.
    Bleeker-Rovers C, van der Ven A, Zomer B, et al. F-18-Fluorodexoyglucose positron emission tomography for visualization of lipodystrophy in HIV-infected patients. AIDS 2004;18:2430–2.PubMedGoogle Scholar
  33. 33.
    Tsong Fang H, Colantonio A, Uittenbogaart C. The role of the thymus in HIV infection: a 10 year perspective. AIDS 2008;22:171–4. doi: 10.1097/QAD.0b013e3282f2589b.CrossRefGoogle Scholar
  34. 34.
    Hardy G, Worrell S, Hayes P, et al. Evidence of thymic reconstitution after highly active antiretroviral therapy in HIV-1 infection. HIV Med 2004;5:67–73. doi: 10.1111/j.1468-1293.2004.00187.x.PubMedCrossRefGoogle Scholar
  35. 35.
    Hoffman JM, Waskin HA, Schifter T, et al. FDG-PET in differentiating lymphoma from nonmalignant central nervous system lesions in patients with AIDS. J Nucl Med 1993;34:567–75.PubMedGoogle Scholar
  36. 36.
    Villringer K, Jager H, Dichgans M, et al. Differential diagnosis of CNS lesions in AIDS patients by FDG-PET. J Comput Assist Tomogr 1995;19:532–6. doi: 10.1097/00004728-199507000-00004.PubMedCrossRefGoogle Scholar
  37. 37.
    Heald A, Hoffman JM, Bartlett J, Waskin H. Differentiation of central nervous system lesions in AIDS patients using positron emission tomography (PET). Int J STD AIDS 1996;7:337–46. doi: 10.1258/0956462961918239.PubMedCrossRefGoogle Scholar
  38. 38.
    O’Doherty M, Barrington S, Campbell M, Lowe J, Bradbeer C. PET scanning and the human immunodeficiency virus-positive patient. J Nucl Med 1997;38:1575–83.PubMedGoogle Scholar
  39. 39.
    Boska M, Mosley R, Nawab M, et al. Advances in neuroimaging for HIV-1 associated neurological dysfunction: clues to the diagnosis, pathogenesis and therapeutic monitoring. Curr HIV Res 2004;2:61–78. doi: 10.2174/1570162043485095.PubMedCrossRefGoogle Scholar
  40. 40.
    Depas G, Chiron C, Tardieu M, et al. Functional brain imaging in HIV-1-infected children born to seropositive mothers. J Nucl Med 1995;36:2169–74.PubMedGoogle Scholar
  41. 41.
    Hinkin C, Van Gorp W, Mandelkern M, 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;7:180–7.PubMedGoogle Scholar
  42. 42.
    Newton T, Leuchter A, Walter D, et al. EEG coherence in men with AIDS: association with subcortical metabolic activity. J Neuropsychiatry Clin Neurosci 1993;5:316–21.PubMedGoogle Scholar
  43. 43.
    Rottenberg D, Sidtis J, Strother S, et al. Abnormal cerebral glucose metabolism in HIV-1 seropositive subjects with and without dementia. J Nucl Med 1996;37:1133–41.PubMedGoogle Scholar
  44. 44.
    Villemagne V, Phillips R, Liu X, et al. Peptide T and glucose metabolism in AIDS dementia complex. J Nucl Med 1996;37:1177–80.PubMedGoogle Scholar
  45. 45.
    von Giesen H, Antke C, Hefter H, Wenserski F, Seitz R, Arendt G. Potential time course of human immunodeficiency virus type 1-associated minor motor deficits: electrophysiologic and positron emission tomography findings. Arch Neurol 2000;57:1601–7. doi: 10.1001/archneur.57.11.1601.CrossRefGoogle Scholar
  46. 46.
    Rottenberg D, Moeller J, Strother S, et al. The metabolic pathology of the AIDS dementia complex. Ann Neurol 1987;22:700–6. doi: 10.1002/ana.410220605.PubMedCrossRefGoogle Scholar
  47. 47.
    Van Gorp W, Mandelkern M, Gee M, et al. Cerebral metabolic dysfunction in AIDS: findings in a sample with and without dementia. J Neuropsychiatry Clin Neurosci 1992;4:280–7.PubMedGoogle Scholar
  48. 48.
    Pascal S, Resnick L, Barker W, et al. Metabolic asymmetries in asymptomatic HIV-1 seropositive subjects: relationship to disease onset and MRI findings. J Nucl Med 1991;32:1725–9.PubMedGoogle Scholar
  49. 49.
    Rock R, Peterson P. Microglia as a pharmacological target in infectious and inflammatory diseases of the brain. J Neuroimmune Pharmacol 2006;1:117–26. doi: 10.1007/s11481-006-9012-8.PubMedCrossRefGoogle Scholar
  50. 50.
    Banati R, Goerres G, Myers R, et al. [11C](R)-PK11195 positron emission tomography imaging of activated microglia in vivo in Rasmussen's encephalitis. Neurology 1999;53:2199–203.PubMedGoogle Scholar
  51. 51.
    Cagnin A, Myers R, Gunn R, et al. In vivo visualization of activated glia by [11C] (R)-PK11195-PET following herpes encephalitis reveals projected neuronal damage beyond the primary focal lesion. Brain 2001;124:2014–27. doi: 10.1093/brain/124.10.2014.PubMedCrossRefGoogle Scholar
  52. 52.
    Cagnin A, Brooks D, Kennedy A, et al. In-vivo measurement of activated microglia in dementia. Lancet 2001;358:461–7. doi: 10.1016/S0140-6736(01)05625-2.PubMedCrossRefGoogle Scholar
  53. 53.
    Hammoud D, Endres C, Chander A, et al. Imaging glial cell activation with [11C]-R-PK11195 in patients with AIDS. J Neurovirol 2005;11:346–55. doi: 10.1080/13550280500187351.PubMedCrossRefGoogle Scholar
  54. 54.
    Wiley C, Lopresti B, Becker 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;12:262–71.PubMedCrossRefGoogle Scholar
  55. 55.
    Wang G, Chang L, Volkow N, et al. Decreased brain dopaminergic transporters in HIV-associated dementia patients. Brain 2004;127:2452–8. doi: 10.1093/brain/awh269.PubMedCrossRefGoogle Scholar
  56. 56.
    Chang L, Wang G, Volkow N, et al. Decreased brain dopamine transporters are related to cognitive deficits in HIV patients with or without cocaine abuse. Neuroimage 2008;42:869–78. doi: 10.1016/j.neuroimage.2008.05.011.PubMedCrossRefGoogle Scholar
  57. 57.
    Bonnet F, Chêne G. Evolving epidemiology of malignancies in HIV. Curr Opin Oncol 2008;20:534–40.PubMedCrossRefGoogle Scholar
  58. 58.
    Powles T, Robinson D, Stebbing J, et al. Highly active antiretroviral therapy and the incidence of non-AIDS-defining cancers in people with HIV infection. J Clin Oncol 2009;27:884–90.PubMedCrossRefGoogle Scholar
  59. 59.
    Bedimo R. Non-AIDS-defining malignancies among HIV-infected patients in the highly active antiretroviral therapy era. Curr HIV/AIDS Rep 2008;5:140–9. doi: 10.1007/s11904-008-0022-4.PubMedCrossRefGoogle Scholar
  60. 60.
    Crum-Cianflone N, Hullsiek K, Marconi V, et al. Trends in the incidence of cancers among HIV-infected persons and the impact of antiretroviral therapy: a 20-year cohort study. AIDS 2009;2:41–50. doi: 10.1097/QAD.0b013e328317cc2d.CrossRefGoogle Scholar
  61. 61.
    Mayor A, Gomez M, Rios-Olivares E, Hunter-Mellado R. AIDS-defining neoplasm prevalence in a cohort of HIV-infected patients, before and after highly active antiretroviral therapy. Ethn Dis 2008;18(2 Suppl 2):S2-189–S2-194.Google Scholar
  62. 62.
    Chitale A. Cancer and AIDS. Indian J Pathol Microbiol 2005;48:151–60.PubMedGoogle Scholar
  63. 63.
    Price R, Spudich S. Antiretroviral therapy and central nervous system HIV type-1 infection. J Infect Dis 2008;197:S294–S306. doi: 10.1086/533419.PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2009

Authors and Affiliations

  • Mike Sathekge
    • 1
  • Ingeborg Goethals
    • 2
  • Alex Maes
    • 3
  • Christophe van de Wiele
    • 2
    Email author
  1. 1.Department of Nuclear MedicineUniversity Hospital of PretoriaPretoriaSouth Africa
  2. 2.Department of Nuclear MedicineUniversity Hospital GhentGhentBelgium
  3. 3.Department of Nuclear MedicineAZ GroeningKortrijkBelgium

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