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HIV Associated Neurocognitive Disorders in the Modern Antiviral Treatment Era: Prevalence, Characteristics, Biomarkers, and Effects of Treatment

  • Central Nervous System and Cognition (I Grant, Section Editor)
  • Published:
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Abstract

The introduction of combination antiretroviral treatment (cART) has significantly reduced the mortality secondary to opportunistic infections in HIV patients by restoring the immune system. In the central nervous system (CNS), there has also been benefit with a marked reduction of HIV associated dementia. However, the milder forms of HIV associated neurocognitive disorder (HAND), namely asymptomatic neurocognitive impairment and mild neurocognitive disorder, remain prevalent in the cART era. In this article, we will discuss how cART interacts with HAND in terms of clinical characteristics and biomarkers. We will then review the outcomes of recent clinical studies focused on the CNS penetrating antiretroviral regimens and some novel therapeutic approaches.

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References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Brew BJ. AIDS dementia complex. In: Brew BJ, editor. Chapter 6, HIV neurology 276 pp. Oxford University Press; 2001.

  2. McArthur JC, Brew BJ, Nath A. Neurological complications of HIV infection. Lancet Neurol. 2005;4(9):543–55.

    Article  PubMed  Google Scholar 

  3. Robertson KR, Smurzynski M, Parsons TD, Wu K, Bosch RJ, Wu J, et al. The prevalence and incidence of neurocognitive impairment in the HAART era. AIDS. 2007;21:1915–21.

    Article  PubMed  Google Scholar 

  4. Marcotte TD, Heaton RK, Wolfson T, Taylor MJ, Alhassoon O, Arfaa K, et al. The impact of HIV-related neuropsychological dysfunction on driving behavior. The HNRC Group. J Int Neuropsychol Soc. 1999;5(07):579–92.

    CAS  PubMed  Google Scholar 

  5. Albert SM, Marder K, Dooneief G, Bell K, Sano M, Todak G, et al. Neuropsychologic impairment in early HIV infection. A risk factor for work disability. Arch Neurol. 1995;52:525–30.

    Article  CAS  PubMed  Google Scholar 

  6. Hinkin CH, Castellon SA, Durvasula RS, Hardy DJ, Lam MN, Mason KI, et al. Medication adherence among HIV + adults: effects of cognitive dysfunction and regimen complexity. Neurology. 2002;59:1944–50.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  7. Bangsberg DR, Moss AR, Deeks SG. Paradoxes of adherence and drug resistance to HIV antiretroviral therapy. J Antimicrob Chemother. 2004;53(5):696–9.

    Article  CAS  PubMed  Google Scholar 

  8. Wilkie FL, Goodkin K, Eisdorfer C, Feaster D, Morgan R, Fletcher MA, et al. Mild cognitive impairment and risk of mortality in HIV-1 infection. J Neuropsychiatry Clin Neurosci. 1998;10(2):125–32.

    CAS  PubMed  Google Scholar 

  9. Sacktor NC, Bacellar H, Hoover DR, Nance-Sproson TE, Selnes OA, Miller EN, et al. Psychomotor slowing in HIV infection: a predictor of dementia. AIDS and death. J Neurovirol. 1996;2:404–10.

    Article  CAS  PubMed  Google Scholar 

  10. 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.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  11. Cysique LA, Brew BJ. Prevalence of non-confounded HIV-associated neurocognitive impairment in the context of plasma HIV RNA suppression. J Neurovirology. 2011;17(2):176–83.

    Article  Google Scholar 

  12. Cysique LA, Maruff P, Brew BJ. Variable benefit in neuropsychological function in HIV-infected HAART-treated patients. Neurology. 2006;66:1447–50.

    Article  PubMed  Google Scholar 

  13. Sevigny JJ, Albert SM, McDermott MP, McArthur JC, Sacktor N, Conant K, et al. Evaluation of HIV RNA and markers of immune activation as predictors of HIV-associated Dementia. Neurology. 2004;63:2084–90.

    Article  CAS  PubMed  Google Scholar 

  14. 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.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  15. McCutchan JA, Marquie-Beck JA, Fitzsimons CA, Letendre SL, Ellis RJ, Heaton RK, et al. Role of obesity, metabolic variables, and diabetes in HIV-associated neurocognitive disorder. Neurology. 2012;78(7):485–92.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  16. Soontornniyomkij V, Umlauf A, Chung SA, Cochran ML, Soontornniyomkij B, Gouaux B, et al. HIV protease inhibitor exposure predicts cerebral small vessel disease. AIDS. 2014;15.

  17. Valcour V, Watters MR, Williams AE, Sacktor N, McMurtray A, Shikuma C. Aging exacerbates extrapyramidal motor signs in the era of highly active antiretroviral therapy. J Neurovirol. 2008;14:362–7.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  18. Tisch S, Brew B. Parkinsonism in HIV-infected patients on highly active antiretroviral therapy. Neurology. 2009;73:401–3.

    Article  PubMed  Google Scholar 

  19. Zhou D, Masliah E, Spector SA. Autophagy is increased in postmortem brains of persons with HIV-1-associated encephalitis. J Infect Dis. 2011;203(11):1647–57.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  20. Alirezaei M, Kiosses WB, Flynn CT, Brady NR, Fox HS. Disruption of neuronal autophagy by infected microglia results in neurodegeneration. PLoS One. 2008;3(8):e2906.

    Article  PubMed Central  PubMed  Google Scholar 

  21. Ardley HC, Scott GB, Rose SA, Tan NG, Robinson PA. UCH-L1 aggresome formation in response to proteasome impairment indicates a role in inclusion formation in Parkinson's disease. J Neurochem. 2004;90:379–91.

    Article  CAS  PubMed  Google Scholar 

  22. McNaught KS, Belizaire R, Isacson O, Jenner P, Olanow CW. Altered proteasomal function in sporadic Parkinson’s disease. Exp Neurol. 2003;179:38–46.

    Article  CAS  PubMed  Google Scholar 

  23. Nguyen TP, Soukup VM, Gelman BB. Persistent hijacking of brain proteasomes in HIV-associated dementia. Am J Pathol. 2010;6(2):893–902.

    Article  Google Scholar 

  24. Cassol E, Misra V, Dutta A, Morgello S, Gabuzda D. Cerebrospinal fluid metabolomics reveals altered waste clearance and accelerated aging in HIV patients with neurocognitive impairment. AIDS. 2014 May 6. This article highlighted the overlapping between HAND and aging in CSF metabolites point of view.

  25. Everall I, Vaida F, Khanlou N, Lazzaretto D, Achim C, Letendre S, et al. Cliniconeuropathologic correlates of human immunodeficiency virus in the era of antiretroviral therapy. J Neurovirol. 2009;15:360–70.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  26. Soontornniyomkij V, Moore DJ, Gouaux B, Soontornniyomkij B, Tatro ET, Umlauf A, et al. Cerebral β-amyloid deposition predicts HIV-associated neurocognitive disorders in APOE ε4 carriers. AIDS. 2012;26(18):2327–35.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  27. Chang L, Jiang C, Cunningham E, Buchthal S, Douet V, Andres M, et al. Effects of APOE ε4, age, and HIV on glial metabolites and cognitive deficits. Neurology. 2014 May 21. doi:10.1212/WNL.0000000000000526.

  28. Schrier RD, Gupta S, Riggs P, Cysique LA, Letendre S, Jin H, et al. The influence of HLA on HIV-associated neurocognitive impairment in Anhui, China. PLoS One. 2012;7(5):e32303.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  29. Gisslén M, Krut J, Andreasson U, Blennow K, Cinque P, Brew BJ, et al. Amyloid and tau cerebrospinal fluid biomarkers in HIV infection. BMC Neurol. 2009;22(9):63.

    Article  Google Scholar 

  30. Ances BM, Benzinger TL, Christensen JJ, Thomas J, Venkat R, Teshome M, et al. HIV associated neurocognitive disorder (HAND) is not associated with increased fibrillar amyloid deposits using 11C-PiB in middle-aged HIV + participants. Arch Neurol. 2012;69(1):72.

    Article  PubMed Central  PubMed  Google Scholar 

  31. Tavazzi E, Morrison D, Sullivan P, Morgello S, Fischer T. Brain inflammation is a common feature of HIV-infected patients without HIV encephalitis or productive brain infection. Curr HIV Res. 2014;12(6). This article highlighted extensive inflammation is a key feature of HAND and its existence in CNS is not necessarily dependent on active HIV viral replication.

  32. Power C, Scenes OF, Grim JA, McArthur JC. HIV Dementia Scale: a rapid screening test. J Acquir Immune Defic Syndr Hum Retrovirol. 1995;8:273–8.

    Article  CAS  PubMed  Google Scholar 

  33. Bottiggi KA, Chang JJ, Schmitt FA, Avison MJ, Mootoor Y, Nath A, et al. The HIV Dementia Scale: predictive power in mild dementia and HAART. J Neurol Sci. 2007;260:11–5.

    Article  PubMed  Google Scholar 

  34. Skinner S, Adewale AJ, DeBlock L, Gill MJ, Power C. Neurocognitive screening tools in HIV/AIDS: comparative performance among patients exposed to antiretroviral therapy. HIV Med. 2009;10:246–52.

    Article  CAS  PubMed  Google Scholar 

  35. Morgan EE, Woods SP, Scott JC, Childers M, Beck JM, Ellis RJ, et al. Predictive validity of demographically adjusted normative standards for the HIV Dementia Scale. J Clin Exp Neuropsychol. 2008;30:83–90.

    Article  PubMed Central  PubMed  Google Scholar 

  36. Lu GM, Brew BJ, Siefried KJ, Draper B, Cysique LA. Is the HIV Dementia Scale a reliable tool for assessing HIV-related neurocognitive decline? J AIDS Clin Res. 2013;5:269.

    Google Scholar 

  37. Cysique LA, Maruff P, Brew BJ. Prevalence and pattern of neuropsychological impairment in human immunodeficiency virus infected/acquired immunodeficiency syndrome (HIV/AIDS) patients across pre and post-highly active antiretroviral therapy eras: a combined study of two cohorts. J Neurovirol. 2004;10:350–7.

    Article  PubMed  Google Scholar 

  38. Edén A, Fuchs D, Hagberg L, Nilsson S, Spudich S, Svennerholm B, et al. HIV-1 viral escape in cerebrospinal fluid of subjects on suppressive antiretroviral treatment. J Infect Dis. 2010;202:1819–25.

    Article  PubMed Central  PubMed  Google Scholar 

  39. Canestri A, Lescure FX, Jaureguiberry S, Moulignier A, Amiel C, Marcelin AG, et al. Discordance between cerebral spinal fluid and plasma HIV replication in patients with neurological symptoms who are receiving suppressive antiretroviral therapy. Clin Infect Dis. 2010;50(5):773–8.

    Article  PubMed  Google Scholar 

  40. Peluso MJ, Ferretti F, Peterson J, Lee E, Fuchs D, Boschini A, et al. Cerebrospinal fluid HIV escape associated with progressive neurologic dysfunction in patients on antiretroviral therapy with well controlled plasma viral load. AIDS. 2012;26:1765–74.

    Article  CAS  PubMed  Google Scholar 

  41. Marcotte TD, Deutsch R, Michael BD, Franklin D, Cookson DR, Bharti AR, et al. A concise panel of biomarkers identifies neurocognitive functioning changes in HIV-infected individuals. J NeuroImmune Pharmacol. 2013;8(5):1123–35.

    Article  PubMed  Google Scholar 

  42. Hagberg L, Cinque P, Gisslen M, Brew BJ, Spudich S, Bestetti A, et al. Cerebrospinal fluid neopterin: an informative biomarker of central nervous system immune activation in HIV-1 infection. AIDS Res Ther. 2010;7:15.

    Article  PubMed Central  PubMed  Google Scholar 

  43. Mellgren A, Price RW, Hagberg L, Rosengren L, Brew BJ, Gisslén M. Antiretroviral treatment reduces increased CSF neurofilament protein (NFL) in HIV-1 infection. Neurology. 2007;69(15):1536–41.

    Article  CAS  PubMed  Google Scholar 

  44. Gisslen M, Hagberg L, Brew BJ, Cinque P, Price RW, Rosengren L. Elevated cerebrospinal fluid neurofilament light protein concentrations predict the development of AIDS dementia complex. J Infect Dis. 2007;195(12):1774–8.

    Article  CAS  PubMed  Google Scholar 

  45. 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;207:1703–12.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  46. Bandaru VV, Mielke MM, Sacktor N, McArthur JC, Grant I, Letendre S, et al. A lipid storage–like disorder contributes to cognitive decline in HIV-infected subjects. Neurology. 2013;81(17):1492–9.

    Article  CAS  PubMed  Google Scholar 

  47. Chang L, Feger U, Ernst TM. Bioimaging. In: Gendelman HE, Grant I, Everall IP, Fox HS, Gelbard HA, Lipton SA, Swindells S, editors. The Neurology of AIDS. Oxford University Press; 2012. p. 763–797.

  48. Alexander AL, Lee JE, Lazar M, Field AS. Diffusion tensor imaging of the brain. Neurotherapeutics. 2007;4(3):316–29.

    Article  PubMed Central  PubMed  Google Scholar 

  49. Filippi CG, Ulug AM, Ryan E, Ferrando SJ, van Gorp W. Diffusion tensor imaging of patients with HIV and normal-appearing white matter on MR images of the brain. Am J Neuroradiol. 2001;22:277–83.

    CAS  PubMed  Google Scholar 

  50. Wu Y, Storey P, Cohen BA, Epstein LG, Edelman RR, Ragin AB. Diffusion alterations in corpus callosum of patients with HIV. Am J Neuroradiol. 2006;27:656–60.

    CAS  PubMed Central  PubMed  Google Scholar 

  51. Chen Y, An H, Zhu H, Stone T, Smith JK, Hall C, et al. White matter abnormalities revealed by diffusion tensor imaging in non-demented and demented HIV + patients. Neuroimage. 2009;47(4):1154–62.

    Article  PubMed  Google Scholar 

  52. Zhu T, Zhong J, Hu R, Tivarus M, Ekholm S, Harezlak J, et al. Patterns of white matter injury in HIV infection after partial immune reconstitution: a DTI tract-based spatial statistics study. J Neurovirology. 2013;19(1):10–23.

    Article  Google Scholar 

  53. Pfefferbaum A, Rosenbloom MJ, Rohlfing T, Kemper CA, Deresinski S, Sullivan EV. Frontostriatal fiber bundle compromise in HIV infection without dementia. AIDS. 2009;23:1977–85.

    Article  PubMed Central  PubMed  Google Scholar 

  54. Wright PW, Heaps JM, Shimony JS, Thomas JB, Ances BM. The effects of HIV and combination antiretroviral therapy on white matter integrity. AIDS. 2012;26:1501–8.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  55. Thurnher MM, Castillo M, Stadler A, Rieger A, Schmid B, Sundgren PC. Diffusion-tensor MR imaging of the brain in human immunodeficiency virus-positive patients. Am J Neuroradiol. 2005;26:2275–81.

    PubMed  Google Scholar 

  56. Chang L, Wong V, Nakama H, Watters M, Ramones D, Miller EN, et al. Greater than age-related changes in brain diffusion of HIV patients after 1 year. J NeuroImmune Pharmacol. 2008;3:265–74.

    Article  PubMed Central  PubMed  Google Scholar 

  57. Pomara N, Crandall DT, Choi SJ, Johnson G, Lim KO. White matter abnormalities in HIV-1 infection: a diffusion tensor imaging study. Psychiatry Res. 2001;106:15–24.

    Article  CAS  PubMed  Google Scholar 

  58. Melrose RJ, Tinaz S, Castelo JM, Courtney MG, Stern CE. Compromise to fronto-stratial functioning in HIV: an FMRI investigation of the semantic event sequencing. Behav Brain Res. 2008;188:337–47.

    Article  PubMed  Google Scholar 

  59. Ernst T, Chang L, Jovicich J, Ames N, Arnold S. Abnormal brain activation on functional MRI in cognitively asymptomatic HIV patients. Neurology. 2002;59:1343–9.

    Article  CAS  PubMed  Google Scholar 

  60. Ances BM, Roc AC, Wang J, Korczykowski M, Okawa J, Stern J, et al. Caudate blood flow and volume are reduced in HIV + neurocognitively impaired patients. Neurology. 2006;66:862–6.

    Article  CAS  PubMed  Google Scholar 

  61. Ances BM, Roc AC, Korczykowski M, Wolf RL, Kolson DL. Combination antiretroviral therapy modulates the blood oxygen level-dependent amplitude in human immunodeficiency virus-seropositive patients. J Neurovirol. 2008;14:418–24.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  62. Thomas JB, Brier MR, Snyder AZ, Vaida FF, Ances BM. Pathways to neurodegeneration: effects of HIV and aging on resting-state functional connectivity. Neurology. 2013;80(13):1186–93. In this fMRI study, the authors demonstrated an independent decrease in baseline brain function in HIV patients similar to aging.

    Article  PubMed Central  PubMed  Google Scholar 

  63. Letendre S, Marquie-Beck J, Capparelli E, Best B, Clifford D, Collier AC, et al. Validation of the CNS penetration-effectiveness rank for quantifying antiretroviral penetration into the central nervous system. Arch Neurol. 2008;65:65–70.

    Article  PubMed Central  PubMed  Google Scholar 

  64. Letendre S, C FitzSimons, R Ellis, Clifford D, Collier A, Gelman B, et al. Correlates of CSF viral load in 1221 volunteers in the CHARTER Cohort. 17th CROI [abstract], San Francisco, CA, USA 2010;430.

  65. Koopmans PP, Ellis R, Best BM, Letendre S. Should antiretroviral therapy for HIV infection be tailored for intracerebral penetration? Neth J Med. 2009;67(6):206–11.

    CAS  PubMed  Google Scholar 

  66. Marra CM, Zhao Y, Clifford DB, Letendre S, Evans S, Henry K, et al. Impact of combination antiretroviral therapy on cerebrospinal fluid HIV RNA and neurocognitive performance. AIDS. 2009;23:1359–66.

    Article  PubMed Central  PubMed  Google Scholar 

  67. Cusini A, Vernazza PL, Yerly S, Decosterd LA, Ledergerber B, Fux CA, et al. Higher CNS penetration-effectiveness of long-term combination antiretroviral therapy is associated with better HIV-1 viral suppression in cerebrospinal fluid. J Acquir Immune Defic Syndr. 2013;62:28–35.

    Article  CAS  PubMed  Google Scholar 

  68. Rawson T, Muir D, Mackie NE, Garvey LJ, Everitt A, Winston A. Factors associated with cerebrospinal fluid HIV RNA in HIV infected subjects undergoing lumbar puncture examination in a clinical setting. J Infect. 2012;65:239–45.

    Article  PubMed  Google Scholar 

  69. Smurzynski M, Wu K, Letendre S, Robertson K, Bosch RJ, Clifford DB, et al. Effects of central nervous system antiretroviral penetration on cognitive functioning in the ALLRT cohort. AIDS. 2011;25:357–65.

    Article  PubMed Central  PubMed  Google Scholar 

  70. Cysique LA, Vaida F, Letendre S, Gibson S, Cherner M, Woods SP, et al. Dynamics of cognitive change in impaired HIV-positive patients initiating antiretroviral therapy. Neurology. 2009;73:342–8.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  71. Tozzi V, Balestra P, Salvatori MF, Vlassi C, Liuzzi G, Giancola ML, et al. Changes in cognition during antiretroviral therapy: comparison of 2 different ranking systems to measure antiretroviral drug efficacy on HIV-associated neurocognitive disorders. JAIDS. 2009;52:56–63.

    CAS  PubMed  Google Scholar 

  72. Ciccarelli N, Fabbiani M, Colafigli M, Trecarichi EM, Silveri MC, Cauda R, et al. Revised central nervous system neuropenetration-effectiveness score is associated with cognitive disorders in HIV-infected patients with controlled plasma viraemia. Antivir Ther. 2013;18:153–60.

    Article  PubMed  Google Scholar 

  73. Casado JL, Marín A, Moreno A, Iglesias V, Perez-Elías MJ, Moreno S, et al. Central nervous system antiretroviral penetration and cognitive functioning in largely pretreated HIV-infected patients. J Neurovirol. 2014;1–8

  74. Vassallo M, Durant J, Biscay V, Lebrun-Frenay C, Dunais B, Laffon M, et al. Can high central nervous system penetrating antiretroviral regimens protect against the onset of HIV-associated neurocognitive disorders? AIDS. 2014;28(4):493–501.

    Article  CAS  PubMed  Google Scholar 

  75. Cross HM, Combrinck MI, Joska JA. HIV-associated neurocognitive disorders: antiretroviral regimen, central nervous system penetration effectiveness, and cognitive outcomes. S Afr Med J. 2013;103(10):758–62.

    Article  CAS  PubMed  Google Scholar 

  76. Ellis RJ, Letendre S, Vaida F, Haubrich R, Heaton RK, Sacktor N, et al. Randomized trial of CNS-targeted antiretrovirals for HIV-associated neurocognitive disorder. Clin Infect Dis. 2013;cit921.

  77. Mind Exchange Group. Assessment, diagnosis, and treatment of HIV-associated neurocognitive disorder: a consensus report of the mind exchange program. Clin Infect Dis. 2013;56(7):1004–17. A comprehensive review and advice on most of clinical issues in managing HAND was made in this consensus.

    Article  Google Scholar 

  78. Brew BJ, Halman M, Catalan J, Sacktor N, Price RW, Brown S, et al. Factors in AIDS dementia complex trial design: results and lessons from the abacavir trial. PLoS Clin Trials. 2007;2(3):e13.

    Article  PubMed Central  PubMed  Google Scholar 

  79. Tozzi V, Narciso P, Galgani S, Sette P, Balestra P, Gerace C, et al. Effects of zidovudine in 30 patients with mild to end-stage AIDS dementia complex. AIDS. 1993;7(5):683–92.

    Article  CAS  PubMed  Google Scholar 

  80. Churchill MJ, Wesselingh SL, Cowley D, Pardo CA, McArthur JC, Brew BJ, et al. Extensive astrocyte infection is prominent in human immunodeficiency virusassociated dementia. Ann Neurol. 2009;66:253–8.

    Article  PubMed  Google Scholar 

  81. Wang Z, Pekarskaya O, Bencheikh M, Chao W, Gelbard HA, Ghorpade A, et al. Reduced expression of glutamate transporter EAAT2 and impaired glutamate transport in human primary astrocytes exposed to HIV-1 or gp120. Virology. 2003;312:60–73.

    Article  CAS  PubMed  Google Scholar 

  82. Patton HK, Zhou ZH, Bubien JK, Benveniste EN, Benos DJ. gp120-induced alterations of human astrocyte function: Na(+)/H(+) exchange, K(+) conductance, and glutamate flux. Am J Physiol Cell Physiol. 2000;279:C700–8.

    CAS  PubMed  Google Scholar 

  83. Eugenin EA, Clements JE, Zink MC, Berman JW. Human immunodeficiency virus infection of human astrocytes disrupts blood–brain barrier integrity by a gap junction-dependent mechanism. J Neurosci. 2011;31:9456–65. Eugenin et al. demonstrated how blood brain barrier disruption and bystander apoptosis are carried out by infected astrocytes via gap junction. This finding offer a possible explanation to cognitive decline despite effective serum viral suppression by cART.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  84. Eugenin EA, Berman JW. Cytochrome C dysregulation induced by HIV infection of astrocytes results in bystander apoptosis of uninfected astrocytes by an IP(3) and Calcium dependent mechanism. J Neurochem. 2013;127(5):644–51.

    Article  CAS  PubMed  Google Scholar 

  85. Gray LR, Tachedjian G, Ellett AM, Roche MJ, Cheng WJ, Guillemin GJ, et al. The NRTIs lamivudine, stavudine and zidovudine have reduced HIV-1 inhibitory activity in astrocytes. PLoS One. 2013;8(4):e62196. This study demonstrated a different inhibitory efficacy profile in targeting astrocytes HIV infection by various ARVs. It provides new consideration in regarding individual ARV CNS penetrating effectiveness in future.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  86. Desplats P, Dumaop W, Smith D, Adame A, Everall I, Letendre S, et al. Molecular and pathologic insights from latent HIV-1 infection in the human brain. Neurology. 2013;80:1415–23. Desplats et al. offered a new concept of latent HIV infection in CNS that could contribute ongoing neuroinflammation without active HIV viral replication.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  87. Sacktor N, Miyahara S, Deng L, Evans S, Schifitto G, Cohen B, et al. Minocycline treatment for HIV-associated cognitive impairment results from a randomized trial. Neurology. 2011;77(12):1135–42.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  88. Brew BJ. Lost in translation: again, another failed neuroprotection trial. Neurology. 2007;69(13):1308–9.

    Article  PubMed  Google Scholar 

  89. Fazeli PL, Woods SP, Heaton RK, Umlauf A, Gouaux B, Rosario D, et al. An active lifestyle is associated with better neurocognitive functioning in adults living with HIV infection. J Neurovirol. 2014;20(3):233–42.

    Article  PubMed  Google Scholar 

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Phillip Chan and Bruce J. Brew declare that they have no conflict of interest.

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Authors and Affiliations

  1. University of New South Wales, St Vincent’s Clinical School, Sydney, Australia

    Bruce J. Brew

  2. Neurology & HIV Departments, St. Vincent’s Hospital, Sydney, Australia

    Bruce J. Brew

  3. St. Vincent’s Hospital Centre for Applied Medical Research, Sydney, Australia

    Bruce J. Brew

  4. Neurology team, Department of Internal Medicine, Queen Elizabeth Hospital, Hong Kong, Hong Kong

    Phillip Chan

  5. Neurology Department, St Vincent’s Hospital, Darlinghurst, NSW, 2010, Australia

    Phillip Chan

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Chan, P., Brew, B.J. HIV Associated Neurocognitive Disorders in the Modern Antiviral Treatment Era: Prevalence, Characteristics, Biomarkers, and Effects of Treatment. Curr HIV/AIDS Rep 11, 317–324 (2014). https://doi.org/10.1007/s11904-014-0221-0

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