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Updated: Nov 26, 2025
Isolation, Transfection, and Culture of Primary Human Monocytes
Published on: December 16, 2019
Apolipoprotein A-I mimetics attenuate macrophage activation in chronic treated HIV
William Mu1,2, Madhav Sharma1, Rachel Heymans1
1Division of Infectious Diseases.
Objectives:
Despite antiretroviral therapy (ART), there is an unmet need for therapies to mitigate immune activation in HIV infection. The goal of this study is to determine whether the apoA-I mimetics 6F and 4F attenuate macrophage activation in chronic HIV.
Design:
Preclinical assessment of the in-vivo impact of Tg6F and the ex-vivo impact of apoA-I mimetics on biomarkers of immune activation and gut barrier dysfunction in treated HIV.
Methods:
We used two humanized murine models of HIV infection to determine the impact of oral Tg6F with ART (HIV+ART+Tg6F+) on innate immune activation (plasma human sCD14, sCD163) and gut barrier dysfunction [murine I-FABP, endotoxin (LPS), LPS-binding protein (LBP), murine sCD14]. We also used gut explants from 10 uninfected and 10 HIV-infected men on potent ART and no morbidity, to determine the impact of ex-vivo treatment with 4F for 72 h on secretion of sCD14, sCD163, and I-FABP from gut explants.
Results:
When compared with mice treated with ART alone (HIV+ART+), HIV+ART+Tg6F+ mice attenuated macrophage activation (h-sCD14, h-sCD163), gut barrier dysfunction (m-IFABP, LPS, LBP, and m-sCD14), plasma and gut tissue oxidized lipoproteins. The results were consistent with independent mouse models and ART regimens. Both 4F and 6F attenuated shedding of I-FABP and sCD14 from gut explants from HIV-infected and uninfected participants.
Conclusion:
Given that gut barrier dysfunction and macrophage activation are contributors to comorbidities like cardiovascular disease in HIV, apoA-I mimetics should be tested as therapy for morbidity in chronic treated HIV.
