Distinct Lipidomic Signatures in People Living With HIV: Combined Analysis of ACTG 5260s and MACS/WIHS

JCEM, September 2021.

While the field has made huge strides in HIV treatment, HIV and its treatment can cause metabolic complications and the distinct effects of HIV itself and antiretroviral therapy (ART) on specific metabolic pathways are not known. A5260s aimed to better understand whether HIV or HIV medications affect metabolism in the body and whether HIV or its treatment affects how the body handles metabolites, lipids, and sugar.

NWCS 412 utilized novel technology (metabolomics and lipidomics) to assess several hundred metabolites and lipid subspecies that are involved in pathways of cholesterol, sugar control, and fat storage. The study measured these metabolites and lipid subspecies in HIV-seronegative individuals from the Multicenter AIDS Cohort Study/Women’s Interagency HIV Study Combined Cohort Study (MACS/WIHS) and in people living with HIV from A5260s before and after initiating ART [tenofovir/emtricitabine plus atazanavir/ritonavir (ATV/r) or darunavir/ritonavir (DRV/r) or raltegravir (RAL)].

Compared to HIV-seronegative individuals, ART-naïve people living with HIV exhibited an altered metabolome that suggests increased lipid production and increased inflammation. This indicates that HIV itself can change metabolism. People living with HIV taking RAL vs. ATV/r or DRV/r also had more inflammation and alterations in fat metabolism. These findings suggest that people living with HIV could benefit from closer monitoring for metabolic complications after starting HIV treatment, including newer HIV treatments. More studies are needed to further understand the cardiometabolic consequences of HIV and its treatment.

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