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Can semaglutide help the brain in people with HIV?

As mentioned earlier in this issue of TreatmentUpdate, semaglutide is being tested in different populations, including some people with HIV.

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A clinical trial in Ohio randomly assigned participants with HIV who had excess belly fat to receive semaglutide or placebo. 

Participants who received semaglutide followed the schedule below:

  • for the first eight weeks, gradually increasing doses until 1 mg/per week
  • for the subsequent 24 weeks, 1 mg/week

Semaglutide was injected subcutaneously (just under the skin) once weekly (as was placebo).

Participants underwent different assessments, including low-dose X-rays to assess body composition, blood tests and a computerized neurocognitive assessment tool called Cognivue, approved by the U.S. Food and Drug Administration (FDA).

Participants did not have diabetes or cardiovascular disease.

The average profile of participants upon study entry was as follows:

  • age – 53 years
  • 60% assigned male at birth; 40% assigned female at birth
  • 35% were current smokers
  • main ethno-racial groups: Black – 60%; White – 35%
  • body mass index (BMI) – 33 kg/m2
  • CD4+ count – 810 cells/mm3
  • viral load – all participants were suppressed
  • time since HIV diagnosis – 18 years

Results

Overall neurocognitive scores between people on placebo or semaglutide were not different. However, when researchers considered sex and CD4+ count, they found that people on semaglutide had improved visuospatial scores.

The researchers did additional analyses and found that this improvement in one area of neurocognitive function seemed to be related to another effect of semaglutide. People who received this drug had a decreased level of proteins associated with inflammation, such as C-reactive protein and soluble CD163. 

Bear in mind

These results should be seen as preliminary and in need of confirmation. The present study was a sub-analysis of a study that was designed to assess semaglutide’s impact on people with excess weight. Assessing neurocognitive function is complex and there are many aspects to brain health. It is not clear what impact of semaglutide on visuospatial processing has on long-term brain health and cognitive function. 

When the data were presented, factors such as diet, exercise and depression were not apparently considered in the analysis. So, the study’s findings should be considered preliminary.

The present study has provided data that could be used to design a larger, longer and complex study that examines the impact of semaglutide on HIV-related inflammation and the impact of a reduction in inflammation on many aspects of health.

—Sean R. Hosein

REFERENCE:

Atieh O, Baissary J, Wu Q, et al, Semaglutide improves cognitive function in HIV, effect mediated by decrease in inflammation. Program and abstracts of the 32nd Conference on Retroviruses and Opportunistic Infections, March 9-12, 2025, San Francisco. Abstract 172.