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

PURPOSE OF REVIEW: 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.

RECENT FINDINGS: 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.

SUMMARY: 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.