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Low Adherence and CD4 Nadir Associated with Cognitive Performance in HIV-Infected Patients

This study explores the relationship between depression, adherence, and cognitive decline in HIV-infected patients. The study found that low adherence and lower CD4 nadir were associated with cognitive performance.

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Low Adherence and CD4 Nadir Associated with Cognitive Performance in HIV-Infected Patients

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  1. LOW ADHERENCE AND CD4 NADIR ARE ASSOCIATED TO COGNITIVE PERFORMANCE IN HIV-INFECTED PATIENTS Barcelona, June 12thand 13th, 2015 NICOLETTA CICCARELLI1 NICOLETTA.CICCARELLI@GMAIL.COM Grima P2, Fabbiani M1, Borghetti A1, Milanini B1, Lamonica S, Cingolani A1, Murri R1, Cauda R1, Di Giambenedetto S1. 1. Institute of Clinical Infectious Diseases, Catholic University of Sacred Heart, Rome, Italy 2. Division of Infectious Diseases, Santa Caterina Novella Hospital, Galatina, Italy 1

  2. INTRODUCTION HIV-ASSOCIATED NEUROCOGNITIVE DISORDERS (HAND) MILD ASYMPTOMATIC NEUROCOGNITIVE IMPAIRMENT (ANI) HIV INFECTION COGNITIVELY NORMAL NEUROCOGNITIVE DISORDER (MND) HIV-ASSOCIATED DEMENTIA (HAD) NEUROLOGY, 2007 2

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  6. OBJECTIVE  To better explore dynamics between depression and adherence in the expression of cognitive decay in HIV infection 6

  7. Methods • We performed a cross-sectional study by consecutively enrolling HIV+ outpatients on therapy at two clinical centers in Italy. • Exclusion criteria: age<18 years, history of CNS opportunistic infections or other neurologic disorders, active psychiatric disorders, alcoholism or drugs/psychoactive substance abuse, linguistic difficulties for non-native patients. • Relationships between adherence, cognitive performance and depression were investigated by linear or logistic regression analysis. 7

  8. Methods • All patients underwent: • Neurocognitive screening test: the Montreal Cognitive Assessment (MoCA) • Questionnaire investigating self-reported adherence during the last 2 months (Murri et al., JAIDS 2000) • Zung Self-Rating Depression Scale (Zung, Arch Gen Psychiatry, 1965) 8

  9. A brief (10 minutes) 30-item test, free(http://.mocatest.org) and translated in several languages, developed for the screening of patients with Mild Cognitive Impairment (MCI) 9

  10. METHODS-MOCA • More sensitive than the Mini Mental State Examination (MMSE) to detect MCI and mild Alzheimer’s disease in the general population; a score <26 was found to be the optimal cut-off to detect the cognitive impairment (Nasreddine et al., JAGS 2005). • Able to capture impairment caused by cortical and subcortical processes. • Previous studies examined the utility of the MoCA to detect neurocognitive impairment in HIV-infected patients (Valcour et al., CID 2011; Overton et al., J Neurovirol. 2013; Milanini et al., JAIDS 2014; Chartier et al., Journal of the International Association of Providers of AIDS Care 2015). 10

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  12. The scores range from 20 to 80: •20-44 Normal Range •45-59 Mildly Depressed •60-69 Moderately Depressed •70 and above Severely Depressed 12

  13. METHODS-ADHERENCE EVALUATION •Self-administered questionnaire (Murri et al., JAIDS 2000) included questions about: •Self-Reported Adherence by a 0 to 100 Visual Analogue-Scale (VAS); NonAdherence was defined as ≤80%. •Running out of pills before the next clinic visit. •The last time the patients forgot to take therapy (response options included “yesterday”, “last week”, “within 3 or 4 weeks ago”, “never”). 13

  14. Results 14

  15. SAMPLE CHARACTERISTICS (N=108) N (%) or *Median (IQR) 89 (82.4) 47 (39-52) 9 (8.3) 4 (3.7) 13 (8-13) Male Age (years)* Age >60 years Non Italian born Education (years)* Transmission risk factor: Heterosexual IDU MSM Unknown Time from HIV diagnosis (years)* HCV co-infection Past AIDS-defining events 37 (34.3) 17 (15.7) 37 (34.3) 17 (15.7) 12 (5-19) 19 (17.6) 19 (17.6) • • • • Past suboptimal therapy 28 (25.9) Time from starting last cART regimen (months) Time from starting first cART regimen (years)* CPE rank >6 HIV-RNA <50 copies/mL CD4 cell count (cells/µL)* CD4 cell count nadir (cells/µL)* 28 (11-52) 8 (3-14) 91 (84.3) 95 (88.0) 637 (455-820) 210 (102-293) 15

  16. SCORES OBTAINED BY PATIENTS ON MOCA Score Mean (SD) Range Total score Visuospatial/ Excecutive Naming 0-30 23.75 (3.89) 0-5 3.70 (1.40) 0-3 2.92 (1.01) Attention 0-6 5.29 (1.01) Language 0-3 2.36 (0.75) Abstraction 0-2 1.10 (0.82) Memory 0-5 2.47 (1.63) Orientation 0-6 5.91 (0.32) 16

  17. SCORES OBTAINED ON DEPRESSION SCALE AND SELF-REPORTED ADHERENCE QUESTIONNAIRE 34.8 (7.7) (MEAN and SD) ZUNG DEPRESSION SCALE 11 (10.2) (N and %) ZUNG SCORE>44 SELF-REPORTED ADHERENCE>80% 86 (79.6) (N and %) 11 (10.2) (N and %) RUNNING OUT OF PILLS BEFORE THE NEXT CLINIC VISIT VAS “How much of your anti-HIV medications you have taken during the last 2 months? (please put a cross (x) on the line below at the point showing your best guess about how much of your anti-HIV medication you have taken in the 2 last months)” Very good Very bad 0______10______20______30______40______50______60______70______80______90______100 Mean 88.69 (SD 0.20) 17

  18. FACTORS ASSOCIATED WITH TOTAL MOCA SCORE UNIVARIATE ANALYSIS MULTIVARIATE ANALYSIS Variable β (95% CI) P β (95% CI) P Sex (male versus female) 0.46 (-1.49; +2.42) 0.640 Age (per 10 years more) Education (per 1 year more) IDU HCV co-infection Time from HIV diagnosis (per 1 year more) Past AIDS-defining events Time from first cART regimen (per 1 year more) Past suboptimal therapy CPE rank>6 HIV RNA<50 copies/mL CDA cell count (per 100 cells more) CD4 cell count at nadir (per 100 cells more) -0.77 0.54 -0.61 (-2.65; +1.43) -0.59 (-2.54; +1.36) (-1.43; -0.11) (0.38-0.70) 0.023 <0.001 0.46 0.554 0.550 -0.05 (-0.10; +0.10) (0.30-0.62) 0.102 <0.001 -0.04 (-0.13; +0.06) 0.420 -1.61 (-3.54; +0.32) 0.101 -0.08 (-0.21; +0.06) 0.261 -1.20 (-2.89; +0.48) -0.44 (-2.48, +1.61) 1.11 (-1.16; +3.39) 0.159 0.673 0.334 1.35 (-0.57; +3.27) 0.166 0.12 (-0.13; +0.38) 0.350 0.52 (0.18-0.86) 0.003 0.40 (0.10-0.70) 0.009 Abnormal Zung Score -1.27 (-6.79; +4.25) 0.648 -2.55 (-7.17;+2.09) 0.278 VAS (per 10 percentage points more) Running out of pills before the next clinic visit The last time the patients forgot to take therapy 0.44 (-0.46; +0.55) 0.861 -0.29 (-0.07; +0.15) 0.190 -2.76 (-5.16; -0.35) 0.025 -2.42 (-4.67; -0.18) 0.035 -1.48 (-4.16; +1.19) 0.275 18

  19. CORRELATION BETWEEN DEPRESSION SCORE AND SELF-REPORTED ADHERENCE 120 Self-Reported Adherence 100 80 Self-Reported Adherence 60 Linear (Self- Reported Adherence) 40 20 0 0 20 40 60 80 Zung Score Pearson’s r = -0.19; p=0.051 19

  20. ASSOCIATION BETWEEN NONADHERENCE (DEPENDENT VARIABLE) AND ZUNG DEPRESSION SCALE ITEMS (INDEPENDENT VARIABLE) UNIVARIATE ANALYSIS Zung Item OR (95% CI) P 2.22 (1.18-4.17) 0.013 “ “I feel down-hearted and blue” ” 1.74 (1.05-2.87) 0.031 “ “My life is empty” ” ”I don’t’ feel that I am useful and needed” 2.03 (1.10-3.76) 0.023 ”I get tired for no reason” 1.90 (1.09-3.31) 0.023 Notes: Multivariate analysis not performed for a collinearity issue. The table shows only the items with a significant association 20

  21. Discussion •Immunological parameters and adherence independently concur to the cognitive status in HIV+ patients. • Our results confirm the association between NonAdherence and Depression, and highlight the need for interventions aimed at preventing or early treating mental disorders. Certain items on depression rating scales may be more indicative of suboptimal adherence than others (Castellon et al., J Clin Exp Neuropsychol. 2006). • In our population there were few subjects with depression (about 10%), probably because we excluded patients with active psychiatric disorders (as major depression) in order to avoid confounding factors when interpreting the cognitive performance. Moreover, our sample included few women (about 18%) who present higher prevalence of depression compared with HIV+ men (Wisniewski et al., J Neurovirol. 2005). • Despite the MoCA is a useful cognitive screening test in HIV+ patients, we need to confirm our results by a more comprehensive neuropsychological investigation. 21

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