Intranasal insulin boosts attention, memory in people with HIV

Treatment with intranasal insulin (INI) improves the performance of virally suppressed people with HIV (VS-PWH) on neuropsychological tests related to memory and attention, according to a study presented at the virtual Conference on Retroviruses and Opportunistic Infections (CROI) 2021.

“Despite suppression of HIV replication with antiretroviral therapies (ART), cognitive impairment (CI) remains prevalent in VS-PWH,” according to researchers led by Anne D. Yacoub, MD, from The John Hopkins University School of Medicine in Baltimore, US.

“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,” they added.

A randomized, double-blind, placebo-controlled study was conducted to determine whether INI would enhance brain energetics in VS-PWH with consequent improvements in cognition. Twenty-one nondiabetic VS-PWH with mild-to-moderate CI were randomly allocated to receive INI (20 IU/day/nare) or placebo. Participants completed standardized neuropsychological tests at baseline, 12, and 24 weeks. Best available norms were used to create demographically adjusted Z-scores for each outcome.

The primary outcomes were Global Deficit Score (GDS), NPZ-8, and performance on individual neuropsychological tests. Then, the researchers conducted a series of mixed-effects regressions to assess the change in cognitive performance over 24 weeks as a function of Treatment Group. Models were adjusted for depressive symptoms.

Forty-five candidates were identified, of whom 21 met the eligibility criteria. Those with insufficient CI (n=10) and current illicit drug use (n=8) were excluded from the trial.

No serious adverse events were reported. Six participants, however, discontinued the study early because of nasopharyngeal irritation (n=3), noncompliance (n=2), and unrelated medical illness (n=1). No significant treatment group differences at baseline were observed on any neuropsychological outcome (p>0.05 for all comparisons; Student’s t-test). [CROI 2021, abstract 337]

In a mixed effects regression of GDS over time with cross-product between INI and time, a significant treatment group effect (p=0.029) was seen with improved GDS at 12 and 24 weeks in VS-PWH who received INI relative to placebo participants.

Improvements on individual neuropsychological tests were evident in the INI group compared to placebo on the following measures: verbal memory (Hopkins Verbal Learning Test—Revised delayed free recall, p=0.028) between baseline and 24 weeks, visual memory (Rey delayed recall, p=0.002), and attention (Trail Making Test-Part A, p=0.006) between baseline and 12 weeks. No treatment group differences were seen over time on the NPZ-8.

“These findings warrant further investigation of intranasal insulin as a cognitive enhancer in VS-PWH,” the researchers said.

An earlier study involving conventional EcoHIV-infected mice showed that INI treatment reverses CI, indicating that the behavioural defects and physiological changes in brains of these mice may be used to create a model of HIV-neurocognitive impairment in HIV-positive people on ART. [AIDS 2019;33:973-984]