This is a Project Grant award from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), under the Diabetes, Digestive, and Kidney Diseases Extramural Research program (CFDA 93.847). The award, totaling $707,929, will support research to define the cellular and molecular processes underlying weight gain associated with the use of integrase strand transfer inhibitor (INSTI) HIV drugs.
The key objectives are to: 1) Investigate the mechanism by which INSTI-based antiretroviral therapy disrupts metabolism and leads to weight gain through the estrogen receptor in adipose tissue, using transgenic mouse models; 2) Evaluate the effects of estrogen on INSTI-mediated weight gain over time in non-human primates infected with SIV; and 3) Assess the impact of INSTI-based therapy on thermogenic pathways and mitochondrial function in adipose tissue from people living with HIV starting INSTI treatment. The research will utilize biochemical, molecular, and multi-omics analyses to elucidate the underlying mechanisms. This work aims to provide insights into INSTI-associated weight gain, particularly in women, and inform strategies to mitigate metabolic dysfunction in people living with HIV.
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