icon-    folder.gif   Conference Reports for NATAP  
  Conference on Retroviruses
and Opportunistic Infections
Will be Virtual
Boston USA
March 6-10, 2021
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  CROI 2021 March 6-10 Reported by Jules Levin
Anne D . Yacoub1, Richard L. Skolasky1, Richard T. Moxley1, Justin McArthur1, Leah Rubin1, Norman D. Haughey1, Ned Sacktor1
1The Johns Hopkins University School of Medicine, Baltimore, MD, USA
Background: Despite suppression of HIV replication with antiretroviral therapies (ART), cognitive impairment (CI) remain prevalent in virally suppressed people with HIV (VS-PWH). Although the precise mechanisms for these residual CI are not fully understood, there is considerable evidence that brain energy metabolism is progressively impaired in VS-PWH. We hypothesized that intranasal insulin (INI) would enhance brain energetics in VS-PWH with consequent improvements in cognition.
Methods: In a randomized, double-blind, placebo-controlled study, 21 non-diabetic VS-PWH with mild-to-moderate CI were randomized to receive INI (20 IU/day/nare) or placebo. Participants completed standardized neuropsychological (NP) tests at baseline, 12, and 24 weeks. Demographically adjusted Z-scores were created for each outcome using the best available norms. Primary outcomes included Global Deficit Score (GDS), NPZ-8, and performance on individual NP tests. A series of mixed-effects regressions were conducted to examine the change in cognitive performance over 24 weeks as a function of Treatment Group. Models were adjusted for depressive symptoms.
Results: Of the 45 candidates screened, 21 met criteria for the study; top reasons for exclusion were insufficient CI (n=10) and current illicit drug use (n=8). No serious study-related adverse events were reported. Six participants discontinued the study early due to naso-pharyngeal irritation (n=3), non-compliance (n=2), and unrelated medical illness (n=1). There were no significant treatment group differences at baseline on any NP outcome (p>.05 for all comparisons; Student's t-test). A mixed effects regression of GDS over time with cross-product between INI and time demonstrated a significant treatment group effect (p.029) with improved GDS in the INI group at 12 and 24-weeks compared with placebo. Improvements on individual NP tests were apparent on measures of verbal memory (HVLT-R delayed free recall, p=.028) between baseline and 24-weeks, on visual memory (Rey delayed recall, p=.002) and attention (Trail Making Test-Part A, p=.006) between baseline and 12-weeks in the INI group compared to placebo. There were no Treatment Group differences over time on the NPZ-8.
Conclusion: In this pilot study, INI improved performance on NP tests related to memory and attention in VS-PWH. These findings warrant further investigation of intranasal insulin as a cognitive enhancer in VS-PWH.