Altered adipose tissue macrophage populations in people with HIV on integrase inhibitor-containing antiretroviral therapy

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

Objective Antiretroviral therapy (ART) extends the life of people with HIV (PWH), but these individuals are at increased risk for obesity, dyslipidemia, diabetes, and cardiovascular disease. These comorbidities may be a consequence of HIV-related chronic inflammation and/or adverse effects of ART on tissue regulatory adipose tissue macrophages (ATMs). We sought to determine the effects of HIV/ART on metabolically beneficial ATM populations and functions. Design We examined subcutaneous ATMs from PWH on integrase inhibitor-containing ART ( n = 5) and uninfected persons ( n = 9). We complemented these studies with ex vivo and in vitro analyses of peripheral blood mononuclear cell (PBMC) and murine macrophage lipid metabolism and fatty acid oxidation gene expression. Methods ATM populations were examined by flow cytometry. Macrophage lipid metabolism and fatty acid oxidation gene expression were examined by Seahorse assay and quantitative PCR. Results Adipose tissue from PWH had reduced populations of metabolically activated CD9 + ATMs compared to that of uninfected controls ( P Conclusions We report the loss of metabolically beneficial ATM populations in PWH on ART, altered fatty acid metabolism of blood immune cells, and evidence that dolutegravir alters macrophage fatty acid metabolism. Future studies should examine direct or indirect effects and mechanisms of dolutegravir, and

Evidence level

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

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