Cognitive Change Trajectories in Virally Suppressed HIV+ Individuals - - PowerPoint PPT Presentation

Cognitive Change Trajectories in Virally Suppressed HIV+ Individuals Suggest High Prevalence of Ongoing Disease Activity

Chloe Gott1 2, Thomas Gates4, Nadene Dermody1 2, Bruce J. Brew2 4, and Lucette A. Cysique2 3 4

1 Psychology Department, Macquarie University, Sydney, NSW, Australia; 2 Faculty of Medicine, University of New South Wales, Sydney, NSW, Australia; 3

Neuroscience Research Australia (NeuRA), Sydney, NSW, Australia; 4 Centre for Applied Medical Research, St Vincent’s Hospital Sydney, NSW, Australia

HIV Endgame I: Closing Gaps in the Care Cascade, October 26tth, 2016 Toronto, Canada OHTN/ISNV

• Presenter: Lucette Cysique
• Relationships with commercial interests
• Grants/Research support: Gilead Science
• Speakers Honoraria: none
• Consulting Fees: none
• Other: none

Presenter Disclosure

Introduction

• Lack of research examining NP changes in individuals with

long‐term viral suppression

• In this context, HAND is mostly characterized by ANI and MND
• Previous studies in cART‐treated patients (N=9) used various

definition of cognitive decline:

• Low clinical relevance
• No practice effect correction
• Absorbing rate vs. multiple rate in multiple study visit
• Single tests or very short NP batteries (tests N=3)
• None of the studies took into account Historical HAND

diagnosis

Study aims

• 1. To quantify the rate of incident neurocognitive decline in

chronic treated HIV+ persons relative to healthy controls of the same age over an 18‐month period based on a test battery that assessed seven cognitive domains

• 2. To investigate the historical and baseline cognitive

determinants of cognitive decline and to determine the profile of cognitive trajectories in functions of historical and baseline HAND status.

• 3. To determine whether standard HIV disease biomarkers &

cART factors contribute to cognitive decline.

Baseline study participants

HIV+ (6% attrition); HIV‐ (12% attrition) Follow‐up assessment ~ 18 months: mean test‐retest interval=19.56 months, SD= 7.73 months. No significant difference between retained & LTFU except for: A higher proportion of HIV+ participants LTFU had HAND at baseline (100%) compared to those retained (55%) (p=.03)

HIV+ sample HIV disease characteristics

88% of HIV+ participants had undetectable viral loads during the study period For the remainder, viral detection was in the form of viral blips (median 150 cp/mL, IQR:100‐345) Except for 1 single case of HIV replication beyond blip level who had to stop cART before a specific medical intervention.

NP test battery

Historical HAND; Baseline HAND & Cognitive Decline

Historical HAND Adapted to the HAND 2007 criteria by LC, and reviewed by BJB to reach diagnoses of MND and HAD. Past HAND status was analyzed as a dichotomous variable (yes/no) Baseline HAND

• Frascati HAND classification
• GDS≥ 0.5 & no IADL decline = ANI
• GDS≥ 0.5 & mild/moderate IADL decline = MND
• GDS≥ 1.5 & severe IADL decline = HAD
• Baseline performance was also analyzed using the mean scaled score

Cognitive Decline

• Based on standard regression‐based norms correcting for PE, demographics,

baseline performance and overall competence

• Individual change score averaged into a summary regression‐based changed score
• The summary based change score is like a z‐score with a mean of 0 and a SD of 1
• Clinically significant decline (yes/no) based on a 95% IC around normative mean

Results: Incident cognitive decline

A greater proportion of HIV+ (14.0%) participants declined as compared to HIV‐ cases (4.5%) (non‐significant difference: p=.11, Φ=.13

Results: Determinants of cognitive decline at group level

Baseline HAND and historical HAND were significantly related, wherein participants who had historical HAND were more likely to also have baseline HAND (p=.035).

Baseline performance: β=.86; p<.0001 HAND Hx: 0.06; p=.29 Interaction: =‐0.07; p=.27

Results: HIV; age; HIV*age interaction & cognitive decline

There was no significant HIV status * Age interaction effects (β=‐0.07; p=0.50) on the summary change score, or the psychomotor, or the mental flexibility change score In these models, age remained an independent predictor for verbal fluency (β=‐0.21; p=0.04) and the summary change score (β=‐0.20; p=0.05) Yet, we note that in the same cohort there was a HIV*age effect on reduced neuronal integrity in the frontal white matter assessed by 1H MRS.

Results: Individual Trajectories of Cognitive Decline

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Results: cognitive decline & HIV disease, cART markers

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• There was no relationship between cognitive decline (taking

into account historical and baseline HAND) and traditional HIV disease biomarkers.

• Nadir CD4+ T cell count (p=.68)
• Current CD4+T cell count(p=.16)
• standardized difference CD4+T cell count (p=.72)
• Virologically undetectable during study period (yes/no; p=.72)
• Baseline HIV duration (p=.73)
• Baseline cART duration in months (p=.48)

Conclusions

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• Despite long‐term viral suppression and immune recovery, our

study demonstrates mostly subclinical levels of decline in psychomotor speed and executive functioning.

• These functions are markers of HAND progression.
• 57% of our cohort is undergoing some evolution of their disease

challenging the notion of neurocognitive stability in virally suppressed HIV+ persons.

• Have we identified slow progression of mostly subclinical

deficits?

• Confirmation in larger and more diverse HIV cohorts will be

important (+ women; more diverse cohort being currently recruited)

• No effect of HIV* age & question of survivor bias & NP versus

Imaging

Acknowledgements

We would like to thank the participants for their time. The study was funding by the NHMRC project grant (APP568746; CIA/PI Cysique) and NHMRC Career Development Fellowship (APP1045400; CIA/PI Cysique), and the support of the Peter Duncan Neuroscience Unit at St. Vincent’s Hospital Applied Medical Research Centre (Director: Prof. Brew)

Thank you for your attention