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Valerio Tozzi National Institute for Infectious Diseases L. Spallanzani. Rome, Italy

Prevalence and risk factors for HIV associated neurococognitive disorders (HAND), 1996 to 2010: results from an observational cohort. Valerio Tozzi National Institute for Infectious Diseases L. Spallanzani. Rome, Italy.

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Valerio Tozzi National Institute for Infectious Diseases L. Spallanzani. Rome, Italy

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  1. Prevalence and risk factors for HIV associated neurococognitive disorders (HAND), 1996 to 2010: results from an observational cohort Valerio Tozzi National Institute for Infectious Diseases L. Spallanzani. Rome, Italy Balestra P, Tozzi V, Zaccarelli M, Libertone R, Cataldo G, Liuzzi G, Menichetti S, Giulianelli M, Narciso P, Lorenzini P, Antinori A.

  2. Rationale • HAND 2011 • Still frequent • Often not diagnosed • Increased risk of death (poster TUPE 204) • Reduced adherence • Poor QoL

  3. Objectives • Assess HAND prevalence changes over the past 15 years • Assess HAND risk factors • Assess changes in HAND severity • Assess qualitative changes in HAND neuropsychological profile

  4. Design and Methods • Single site observational study • Inclusion criteria • Indication for starting / being on HAART • Exclusion criteria • confounding neurological, psychiatric, and medical disorders • active drug use

  5. Clinical Methods • Demographics • Medical assessments • Neurological assessments • Standard brain MRI • Routine laboratory, CD4, plasma HIV RNA • Neuropsychological (NP) assessment on 5 domains • Exclusion of confounding conditions

  6. NP Battery and Domains • Memory • Rey Auditory Verbal Learning (immediate) • Rey Auditory Verbal Learning (immediate) • Rey Complex Figure (after 45’) • Fine Motor Functioning • Lafayette Grooved Pegboard (dominant hand) • Lafayette Grooved Pegboard (non dominant hand) • Visuospatial and Constructional Abilities • Rey Complex Figure (copy) • Concentration and Speed of Mental Processing • Trail Making A • WAIS-R Digit Span (forward) • WAIS-R Digit Span (backward) • Digit Symbol • Stroop Word and Colour • Corsi Cube Test • Mental Flexibility • Trail Making B • Stroop Colour-Word • Controlled Oral Word

  7. NP Assessment (I) • Exclusion of confounders (clinical, lab, MRI) • All NP evaluations administered by one of us (P Balestra) to ensure little variability • NP scores adjusted for age, gender, years of education • Compared to population based norms

  8. NP Assessment (II) Cognitive Impairment: 1 SD below the normative mean in  2 tests or 2 SD below the normative mean in  1 test Z-Scores (neg values  performance below the mean) Z-Scores for each NP test Z-Scores for each Cognitive Domain Global NPZ-8 Deficit Score

  9. Diagnostic Criteria • Severity of impairment at NP testing • Declines in everyday functioning by clinical assessment • HAD (HIV Associated Dementia)* • MND (Mild Neurocognitive Disorder)* • ANI (Asymptomatic Neurocognitive Impairment)* * AAN 2007 criteria

  10. Statistics • Comparisons between impaired and unimpaired subjects • t-student test for continue variables • chi-squared for categorical variables • Factors associated with HAND and with HAND severity • logistic regression model

  11. Source Studies and Sample Selection Studies (1996-2010) Sample • ISS, 1° Ntl AIDS Program • ISS, 2° Ntl AIDS Program • ISS, 3° Ntl AIDS Program • ISS, 4° Ntl AIDS Progfam • ISS, 5° Ntl AIDS Program • Ricerca Corrente IRCCS 1.888 cases 469 confounding conditions (excluded) 44 invalid NP test results (excluded) 1.375 cases

  12. Patient’s characteristics (I)

  13. Patient’s characteristics (II)

  14. HAART exposure HAART exposure >52 weeks; p<0.001 23.2% 48.1% 61.3% 73.2% 75.3%

  15. Proportion Impaired (HAND) HAND (3 yrs incr): OR 0.92 (95% CI 0.85-0.99); p=0.031 45.6% 44.4% 39.4% 39.4% 38.2%

  16. Proportion with HAND by CDC stage

  17. HAND predictors, unajusted

  18. HAND predictors by HAART era, unajusted

  19. HAND predictors, multivariable(n=1.375)

  20. Proportion of HAD-MND-ANI HAD + MND (3 yrsincr): OR 0.89 (95% CI 0.82-0.97); p=0.008 29.9% 29.2% 29.9% 27.2% 27.2% 25.4% 29.2% 25.4% 19.4% 18.4%

  21. Symptomatic (HAD/MND) vs asymptomatic (ANI) predictors, unajusted * i.e. diabetes, hypertension, hyperlipedemia, prior myocardial infarction, obesity

  22. Symptomatic (HAD/MND) vs asymptomatic (ANI) predictors, multivariable(n=569)

  23. NPZ-8, HAND (n=569) Mean (±SD) Global z-score β= -0.05; p=0.646

  24. Concentration and Speed of Mental Processing z-scores, HAND (n=569) Mean (±SD) Global z-score Β= -0.08; p=0.263

  25. Mental Flexibility z-scores, HAND (n=569) Mean (±SD) Global z-score b= -0.01; p=0.861

  26. Memory Z-scores, HAND (n=569) Mean (±SD) Global z-score B =-0.05; p=0.234 * visual memory and spatial perception

  27. Rey Complex Figure Test * visual memory and spatial perception

  28. Rey Complex Figure Test Rey Complex Figure Test (after 45’): Score 18.5 (n.v. >16) * visual memory and spatial perception

  29. Rey Complex Figure Test Rey Complex Figure Test (after 45’): Score 18.5 (n.v. >16) Rey Complex Figure Test (after 45’): Score 3.5 (n.v. >16) * visual memory and spatial perception

  30. Fine Motor Functioning Z-scores, HAND (n=569) Mean (±SD) Global z-score b= 0.01; p=0.758

  31. Visuospatial and Constructional Abilities Z-scores, HAND (n=569) Mean (±SD) Global z-score b= 0.02; p=0.620

  32. Based exclusively on NP evaluations (i.e.: no CSF, no advanced MRI) Diagnostic Nomenclature changed in 2007 HAD = HAD MND  retrospectively*, yrs 1996-2007 ANI  retrospectively*, yrs 1996-2007 Patients with confounding (i.e.: liver cirrhosis, current i.v.d.u.) conditions excluded. Role of incidental and contributing conditions (i.e.: HCV, previous i.v.d.u.) not evaluated Study limitations * Based on data on file and previous classifications, by (AAN, 1991) (Grand and Atkinson, 1995) criteria

  33. Conclusions (I) • Cognitive impairment persists • Small, but significant, downtrend in HAND prevalence HAART protective • Strongest predictors of HAND • Low HAART exposure HAART protective • Previous AIDS immunodeficiency • Low current CD4 persistent immunodeciciency • Advanced age time-related cofactors • Low education reduced cognitive reserve

  34. Conclusions (II) • Downtrend in prevalence of symptomatic (HAD/MND) forms of HAND  evidences for milder forms of HAND • Strongest predictors of symptomatic (HAD/MND) vs asymtomatic (ANI) forms of HAND • Advanced age  time-related cofactors • Low education  reduced cognitive reserve • Previous AIDS  immunodeficiency • Low current CD4 persistent immunodeficiency • Cardiovascular risk factors  chronic inflammation

  35. Conclusions (III) Some evidences of less impairment in measures of visual memory and spatial perception Overall, almost no changes in qualitative profile of cognitive impairment (“subcortical profile”, core deficits: attention/memory, motor skills, processing speed, and executive functioning)  very limited evidences for a change in HAND neurocognitive profile

  36. Acknowledgments • Neuropsychologist • Balestra P • Statistician • Lorenzini P • Our patients • IstitutoSuperiorediSanità • Ministerodella Salute • Coauthors • Zaccarelli M • Libertone R • Cataldo G • Liuzzi G • Menichetti S • Giulianelli M • Sampaolesi A • Giannetti A • Picchi G • Narciso P • Antinori A

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