Weight gain, adipose tissue remodeling and cardiometabolic disease in people with HIV

Weight gain and associated adipose tissue remodeling have been partly linked to HIV infection and to some current antiretroviral therapy (ART) regimens in ART-naive and ART-controlled people with HIV (PWH). This review addresses recent findings on adipose tissue distribution and remodeling in PWH, receiving dolutegravir, bictegravir and/or tenofovir alafenamide (TAF), highlighting how visceral adiposity contributes to cardiometabolic comorbidities.

Preclinical models exposed to dolutegravir, bictegravir, tenofovir disoproxil fumarate (TDF) and/or TAF demonstrate alterations in adipose tissue, including mitochondrial dysfunction, fibrosis, inhibited beiging, and insulin resistance. Transcriptomic studies of abdominal subcutaneous fat from ART-controlled PWH further revealed elevated inflammation, fibrosis and insulin resistance. Increased visceral adiposity raises the risk of cardiometabolic disorders such as insulin resistance and diabetes, metabolic-dysfunction-associated steatotic liver disease and cardiovascular diseases. Reversing weight gain linked to ART, by switching regimens or adding antiobesity medications like the GLP-1 receptor agonist semaglutide, has shown potential in reducing adipose tissue remodeling, visceral adiposity and cardiometabolic risk factors.

Weight gain and increased visceral adiposity partly driven by some ARTs are associated with higher cardiometabolic risk. HIV and ART can either activate or suppress the fat beiging/browning phenotype. Reversing weight gain and visceral adiposity in at-risk PWH is a critical clinical goal.