Dolutegravir (Tivicay, also found in Triumeq and Dovato) and raltegravir (Isentress), both integrase inhibitors commonly used in HIV treatments, can change the structure of fat cells and cause insulin resistance, French researchers reported at the 17th European AIDS Conference in Basel, Switzerland.
The researchers studied cells from people who had been taking dolutegravir or raltegravir. Previous studies have suggested that people taking an integrase inhibitor were more likely to gain weight, but until now it wasn't clear exactly why or how.
There are two types of adipose tissue: brown fat (also known as visceral fat), which accumulates around the organs and in the abdomen; and white or subcutaneous fat, which accumulates just under the skin.
Researchers discovered that dolutegravir and raltegravir may have a direct effect on these fatty tissues because they are associated with lower levels of leptin, a hormone that decreases appetite, and adiponectin, a hormone that manages how our cells store glucose, a primary source of energy.
After studying two groups of monkeys, where one group was on a regimen of dolutegravir, tenofovir and emtricitabine; or raltegravir, tenofovir and emtricitabine; and another group received no treatment: greater fibrosis (or a high formation of excess tissue) was found in the adipose tissue of the monkeys exposed to antiretroviral therapy.
As for humans, the researchers analyzed fat cell samples from 14 people living with HIV who underwent weight loss surgery; some took integrase inhibitors and others did not.
The data showed that 80 percent of the subjects had fibrosis in their subcutaneous adipose tissue, and 70 percent of these had fibrosis in their visceral adipose tissue. Some scientists believe that fibrosis contributes to insulin resistance, which can cause diabetes and heart disease.
To better understand the impact of integrase inhibitors on fat cells, researchers studied adipose stem cells from HIV-negative women. The scientists discovered that cells exposed to dolutegravir or raltegravir in the laboratory produced more types of collagen associated with obesity and fibrosis in adipocytes, a specialized type of fat cell. The drugs were also associated with increased fat cell production and lipid storage, as well as lower leptin levels and reduced glucose uptake.
A previous literature review in JCI Insight noted that fibrosis within adipose tissue could influence the development of obesity or obesity-related comorbidities, but this connection has not yet been conclusively demonstrated. There is no scientific consensus on whether such fibrosis causes or contributes to obesity or is a result of being overweight.
The latest study expands our understanding of how two integrase inhibitors impact adipose tissue. It may not prove that the changes integrase inhibitors cause in fat cells are the drivers of drug-associated weight gain, but the results suggest a correlation.
The authors concluded: “Here we demonstrate for the first time that integrase inhibitors exert a direct impact on adipogenesis, fibrosis, and insulin resistance. These results,
The findings revealing the adipose tissue toxicity of dolutegravir and raltegravir are important in explaining the fat modifications reported in HIV-infected patients treated with INSTI.
From: https://www.hivplusmag.com/treatment/2020/2/13/do-these-hiv-meds-make-my-butt-look-big