Semaglutide improves markers of cardiovascular risk in people with HIV
Lake JE, Kitch DW, Kantor A, Alonso C, Belaunzaran-Zamudio PF, Kulik GL
AIDS (2026) · n=36
In the first lipidomic and lipo-/glyco-protein profiling of semaglutide therapy in any population — 36 adults with HIV and MASLD from the SLIM LIVER (ACTG A5371) trial — semaglutide reduced triglycerides, diglycerides, sphingomyelins, and CVD-linked lipoprotein species; 56% with elevated GlycA improved and 32% normalised, with effects independent of changes in weight, liver fat, or insulin resistance.
This is a secondary analysis of SLIM LIVER (ACTG A5371), an open-label single-arm Phase 2b trial of weekly 1 mg semaglutide in adults with HIV (PWH) and metabolic dysfunction-associated steatotic liver disease, conducted across multiple US sites by the AIDS Clinical Trials Group. The analysis is the first human report of lipidomic and lipo-/glyco-protein profiling during semaglutide therapy in any population. 36 participants with documented clinical response (>5 lb weight loss) provided stored serum for analysis. Median age was 52 years, median BMI 34 kg/m²; 39% were Hispanic, 28% Black, 45% female; 22% were on stable statin therapy.
Lipidomics: semaglutide reduced triglycerides, diglycerides, and sphingomyelins; bile acids and certain phosphatidylcholines increased. Lipoproteins: CVD-linked particle species decreased, LDL particle size increased, and large HDL particle number decreased. Glycoproteins: most participants had elevated baseline GlycA and GlycB (CVD-linked markers of systemic inflammation). 56% with elevated GlycA improved and 32% normalised; 41% with elevated GlycB improved and 42% normalised. Critically, the lipo-/glyco-protein concentration changes did not correlate with baseline weight, baseline liver fat, baseline insulin resistance, or with the magnitude of change in any of those parameters.
The N=36 cohort is small and was restricted to clinical responders (those who lost >5 lb), which biases the analysis toward subjects in whom semaglutide was already biologically active. This is not the full SLIM LIVER intent-to-treat population; non-responders and discontinuers are excluded. The open-label single-arm design has no placebo comparator, so the "independent of weight/liver fat" inference relies on within-subject correlation rather than between-arm contrast.
PWH on antiretroviral therapy carry a complex baseline metabolic phenotype — chronic inflammation, antiretroviral lipodystrophy, integrase-inhibitor-associated weight gain — and the generalisability of the lipidomic signature to non-HIV populations is unestablished.
Funding includes NIAID-supported ACTG infrastructure, and several co-authors disclose pharmaceutical relationships. The 1 mg dose is sub-clinical-target (the obesity-indication dose is 2.4 mg), which may further limit comparison with the SELECT / STEP populations. Abstract-only extraction.
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