Research Summary

Does Semaglutide Improve Cognitive Function in People with HIV Through Reduced Inflammation?

Anthony Calabro, MA

Key Highlights

  • Semaglutide improved visuospatial, language, and delayed recall cognitive scores in people with HIV.
  • Only the visuospatial score remained statistically significant after adjusting for sex and CD4 count.
  • No associations were found between cognitive changes and reductions in adiposity.

Semaglutide was associated with improvements in select cognitive domains among people with HIV (PWH), according to Ornina Atieh, MD and her colleagues who presented their findings at the Conference on Retroviruses and Opportunistic Infections 2025 Annual Meeting in San Francisco, CA.

Participants who received semaglutide demonstrated statistically significant gains in visuospatial, naming/language, and delayed recall scores after 32 weeks of treatment. Following adjustment for confounding variables, the improvement in visuospatial function remained significant. Mediation analysis indicated that this cognitive benefit was driven by reductions in inflammation, as measured by high-sensitivity C-reactive protein (hs-CRP), and not by changes in body fat distribution.

People with HIV are at elevated risk for increased visceral adiposity, systemic inflammation, and neurocognitive decline compared with those without HIV. Prior evidence from the same randomized controlled trial showed that semaglutide reduced body weight, visceral fat, and inflammatory markers in this population. Given the persistent burden of cognitive impairment in PWH despite effective antiretroviral therapy (ART), there is a critical need to identify therapeutic interventions that target the biological pathways contributing to these deficits.

The phase 2B trial was conducted at University Hospitals in Cleveland, OH, and enrolled 108 adult PWH with stable ART regimens, elevated BMI (≥ 25 kg/m²), and increased waist-to-hip ratios. Participants were randomized 1:1 to receive 32 weeks of subcutaneous semaglutide or placebo. Cognitive function was assessed at baseline and at 32 weeks using the FDA-approved Cognivue® test, which evaluates multiple cognitive domains.

At 32 weeks, semaglutide recipients demonstrated statistically significant improvements in visuospatial (P = .01), naming/language (P = .05), and delayed recall (P = .04) scores compared with placebo. After adjusting for sex and CD4 count, only the visuospatial improvement remained significant (P = .05). Mediation analysis revealed that the total natural direct effect of semaglutide on visuospatial performance persisted after accounting for changes in hs-CRP (P = .04), indicating an inflammation-mediated effect. No correlation was observed between cognitive improvements and changes in total or central adiposity.

“Semaglutide has shown a beneficial impact on cognitive function in people with HIV, particularly in relation to visuospatial cognitive function,” Atieh and colleagues concluded. “This effect appears to be mediated by the effect of the drug on inflammation.”

Reference
Atieh O, Baissary J, Wu Q, et al. Semaglutide improves cognitive function in HIV, effect mediated by decrease in inflammation. [CROI Abstract 172]. Abstracts from the Conference on Retroviruses and Opportunistic Infections 2025. Abstract eBook. 2025;171.