Weight gain and altered fat distribution are increasingly recognized problems among people with HIV (PWH). The review identifies both HIV infection and some antiretroviral therapy (ART) regimens as partial drivers of these changes. Specific agents called out include integrase strand transfer inhibitors such as dolutegravir and bictegravir, and newer tenofovir formulations including tenofovir alafenamide (TAF). The phenomena are observed in ART-naive individuals initiating therapy and in ART-controlled PWH.
The clinical concern extends beyond simple increases in body weight: the pattern of fat accumulation and the cellular remodeling of adipose tissue are central to downstream metabolic consequences. In particular, visceral fat accumulation is emphasized as a significant contributor to cardiometabolic risk in this population.
Experimental and preclinical models reported in the review document several mechanistic changes in adipose tissue after exposure to certain ART agents. Observed alterations include mitochondrial dysfunction, increased fibrosis within adipose depots, impaired induction of the beiging/browning program of white adipose tissue, and development of insulin resistance at the tissue level.
These mechanisms offer biological explanations for how ART exposures can produce not only increased adiposity but also qualitative changes in fat that predispose to metabolic dysfunction. The review highlights that different ART agents may exert distinct effects on adipocyte biology and adipose tissue microenvironment.
Molecular profiling of abdominal subcutaneous fat from ART-controlled PWH reveals transcriptomic signatures consistent with heightened inflammation, fibrosis and insulin resistance. These tissue-level findings align with the preclinical observations and indicate that adipose remodeling occurs in humans on long-term ART, even when viral replication is controlled.
Such transcriptomic evidence supports a model in which the adipose depot becomes a site of chronic metabolic and inflammatory dysregulation in some PWH, potentially bridging ART exposure and systemic cardiometabolic disease.
The review links increases in visceral adiposity with elevated risk for several cardiometabolic conditions among PWH. These include insulin resistance and type 2 diabetes, metabolic-dysfunction-associated steatotic liver disease, and cardiovascular disease. Visceral fat is singled out because of its known associations with systemic inflammation, altered lipid and glucose metabolism, and atherogenic risk.
The authors underscore that both absolute weight gain and unfavorable fat redistribution—particularly accumulation of visceral fat—are clinically relevant endpoints when assessing cardiometabolic risk in PWH.
Strategies to reverse ART-associated weight gain and adverse adipose remodeling are discussed. One approach is changing ART regimens away from agents implicated in weight and adipose changes. Another reported strategy is the adjunctive use of antiobesity therapies. The review specifically notes data on the GLP-1 receptor agonist semaglutide as an example of an antiobesity medication that has been used to reduce weight, visceral adiposity and related cardiometabolic risk factors in affected individuals.
The review indicates that these interventions have shown potential to ameliorate adipose tissue remodeling and reduce cardiometabolic risk markers, but it does not provide exhaustive efficacy or safety data within the abstract. Details on specific trials, magnitudes of effect, or long-term outcomes are not reported in the source abstract.
The central clinical message is that weight gain and increased visceral adiposity—partly driven by certain ARTs—are associated with higher cardiometabolic risk in PWH. HIV infection and ART can either promote or inhibit the fat beiging/browning phenotype, which may modulate metabolic consequences.
Given these relationships, the review calls for clinical attention to identifying at-risk patients, monitoring fat distribution and metabolic markers, and pursuing strategies to reverse weight gain and visceral adiposity when appropriate. Reversing these changes is framed as a critical goal to lower cardiometabolic risk in PWH.
The review highlights mechanistic themes—adipogenesis, fat beiging, inflammation, insulin resistance and mitochondrial dysfunction—as areas of focus for understanding and potentially intervening on adipose remodeling in the context of HIV and ART.