HIV og CNS. NB: HIV inficerer ikke neuroner, men makrofager og mikroglia!!! Rev Med Virol2011

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2 CNS og HIV Isolation of HTLV-III from CerebrospinalFluid and Neural Tissues of Patients withneurologicalsymptoms Relatedto Acquired Immunodeficiency Syndrome Ho D et al: New England Journal of Medicine. 12. december 1985

3 HIV og CNS NB: HIV inficerer ikke neuroner, men makrofager og mikroglia!!! Rev Med Virol2011

4 HIV og neuropatogenese Rev Med Virol2011

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6 The AIDS Dementia Complex Memorial Sloan-Kettering(MSK) scale Subcortical dementia: cognitive defects, psychomotor slowing, behavioral abnormalities. J Infectious Diseases 1988; 158;1079

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8 HIV Dementia Scale(HDS): A Rapid Screening Test. Score <10 HIV demens MMSE = Mini-Mental State Exam PB = Grooved Pegboard MMSE er udviklet til vurdering af cortical demens. JAIDS 1995; 8; 273

9 International HIV Dementia Scale(IHDS) Cut-off<10 Ingen krav til sprogkundskaber, kan udføres på 2-3 minutter. Der skal bruges et ur med sekundviser. AIDS 2005; 19; 1367

10 Neurocognitivescreening tools in HIV/AIDS: comparative performance among patients exposed to antiretroviral therapy MMSE failed to discriminate between HIV+ with(hand) and without(ond) neurocognitive impairment HIV Medicine Volume 10, Issue 4, pages , 28 JAN 2009 DOI: /j x

11 Updated research nosology for HIV associated neurocognitive disorders HIV Associated Neurocognitive Disorders(HAND) ANI = asymptomatic neurocognitive impairment MND = HIV-associated mild neurocognitive disorder HAD = HIV-associated dementia Antiniori A et al: Neurology 2007; 69; 1789

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13 CNS Penetration-Effectiveness(CPE) Top HIV Med 2010; 18; 45 LetendreS et al: ArchNeurol2008; 65; 65-70

14 LetendreS et al: ArchNeurol2008; 65; 65-70

15 Nature Reviews Neuroscience 2007; 8; 33

16 Clinical Infectious Diseases 2011; 52;235

17 Clinical Infectious Diseases 2011; 52;235

18 Changesin the Incidenseand Predictorsof HIV associated Dementia in the Era of HAART CASCADE: n = Incidenceof HIV-D per PYR was6.49 pre-1997, declining to 0.66 by Annals of Neurology 2008; 63; 213

19 Neurocognitiveeffectsof treatmentinterruptionin stable HIV-positive patients in an observational study. n = 167 Neurology 2010; 74; 1264

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21 Fig.2NP Domain impairment in pre-cart and CART era HIV+ samples with NCI. SIPspeed of information processing, Learn learning efficiency, Recall delayed recall, Attn/WM attention/working memory, Execexecutive function; *p < 0.05; **p < 0.01; ***p < J. Neurovirology 2011; 17; 3-16

22 Dementia and Neurocognitive Disorders Due to HIV-1 Infection Semin Neurology 2007; 27; 86-92

23 Cognitive dysfunction in HIV patients despite long-standing suppresion of viremia n = /200 (27 %) with complaints AIDS 2010; 24; 1243

24 HIV associatedneurocognitivedisorderspersistin the eraof potent antiretroviral therapy n = AIN 33 %; MND 12 %; HAD 2 % Neurology 2010; 75; 2087

25 Neurology 2010; 75; 2087

26 In summary, neurocognitive functioning is most significantly impacted among the chronically infected. Our study was unable to statistically confirm neurocognitive impairments in the earliest stage of HIV infection, but there is a pattern toward, and non-statistical indicators of, AEH persons showing neurocognitive performance intermediate to HIV controls and persons with chronic HIV. J. Neurovirology 2011; 17; 50-57

27 74 midaldrende (51 år) HIV+ mænd, gennemsnitlig HIV-smittede i 17 år. 32 % med Succesful cognitive ageing.

28 HAND Incidencen af HAD er faldet under HAART Prævalensen af HAND er stigende og er høj hos patienter i behandling med HAART og umålelig HIV-RNA Konsekvenser af HAND Dårlig livskvalitet Arbejdsløshed Dårligere adherence Tidligere død Screening? Behandling?

29 A screening algorithm for HIV-associated neurocognitive disorders SVM = support vector machine Age, current CD4 count, past CNS HIV-related disease, current treatment duration. Takes approximately 3 minutes to complete. Sensitivity 78 %, specificity 70 % HIV Medicine 2010; 11; 642

30 Computer-BasedCognitiveScreening Tool CAMCI = Computer Assesment of Mild Cognitive Impairment Sensitivity 0.72; specificity 0.97, PPV 0.93, NPV 0.72 Calcap = The California Computerised Assesment Package Sensitivity 0.68; specificity 0.77 CogState Sensitivity 0.81; specificity 0.70, overall accuracy of 77 % HIV Medicine 2010; 11; 642 AIDS Patient Careand STDs2011; 25; 351

31 CAMCI CAMCI takes approximately minutes The test is not as anxiety provoking AIDS Patient Careand STDs2011; 25; 351

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33 Clinical Infectious Diseases 2011; 53; 836

34 Screening for neurocognitiveimpairment A study in Switzerland on asymptomatic patients who were virologically supressed on antiretroviral therapy suggest that askingthreesimple questionsmaybehelpfulin screening for symptomatic neurocognitive impairment: 1) Do youexperiencefrequentmemoryloss(e.g. do youforgetthe occurence of special events even the more recent ones, appointments etc.)? 2) Do youhave feelthatyouareslowerwhenreasoning, planning activities, or solving problems? 3) Do youhave difficultiespayingattention (e.g. to a converstion, a book, ora movie)? For each question patient can answer never, hardly ever, or yes definitely. SimioniS et al. AIDS 2010; 24; 1243

35 EACS Guidelines 2011

36 EACS Guidelines 2011

37 EACS Guidelines 2011

38 EACS Guidelines 2011

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