As obesity rates rise in the United States, a corresponding number of HIV-positive patients are overweight and obese when they first start antiretroviral therapy (ART).
Now, mounting observational data suggest that integrase strand transfer inhibitor (INSTI)-based ART may be correlated with weight gain and other metabolic changes. Weight gain among HIV-positive patients can exacerbale other comorbidities -- but should clinicians avoid INSTIs for their overweight and obese patients?
Now, several new posters and late-breaking abstracts presented at the IDWeek conference in Washington, D.C. add new insights to the puzzling link between INSTIs and weight gain.
The first of these new data were presented by Karam C. Mounzer, M.D., clinical professor of medicine at the University of Pennsylvania. "There is growing evidence supporting an increase in weight gain associated with the use of integrase inhibitors, notably dolutegravir," he said during his presentation at IDWeek. However, Mounzer said that most of these studies were conducted among antiretroviral-naive patients and did not adjust for tenofovir alafenamide (TAF) or other medications that can impact weight gain.
The objective of his study was to compare the changes in body mass index (BMI) among ART-experienced, virologically suppressed patients with HIV after they switched to a three-drug regimen including one of the following drugs: dolutegravir (Tivicay, DTG), elvitegravir/cobicistat (EVG/c), raltegravir (Isentress, RAL), rilpivirine (Edurant, RPV), or boosted darunavir (bDRV).
Mounzer and his colleagues used data from the OPERA cohort -- a collaboration of 79 U.S. outpatient clinics. About a quarter of the cohort were women, and over a third were black. The majority of patients were overweight at the time of their regimen switch.
Among those who were overweight at the time of their switch, the adjusted mean BMI increase was statistically smaller with bDRV than DTG (-0.32) after one year. Among patients who were not overweight or obese at the time of switch, the adjusted mean change in BMI was smaller with EVG/c, bDRV, and RAL than DTG (range -0.26 to -0.27).
Although these small differences appeared to favor EVG/c, RAL, and bDRV over DTG, Mounzer noted that those changes were small.
"There was no real difference between all five core agents," he said. "There's an upward trend. [But] it almost seems like everyone seems to be gaining weight as time goes by."
An abstract presented by Matty Zimmerman, a student pharmacist at the Jefferson College of Pharmacy, also highlighted the complex interplay of INSTI-associated weight gain and other metabolic outcomes.
The retrospective study looked at changes in weight, BMI, cholesterol, and A1c among virally suppressed people living with HIV who switched to an INSTI-based regimen from May 2015 to December 2017 at a single academic medical center. The majority of the cohort were men, and just over half were black.
A total of 90 patients met the criteria for analysis, and their outcomes were measured up to 18 months after the switch. Zimmerman and colleagues found significant increases in weight and BMI after the switch, but they did not find significant changes in A1c or cholesterol. Patients who switched gained an average of 2.2 kg, though about a quarter gained more than 4.5 kg.
A third abstract presented at IDWeek also looked beyond weight gain, evaluating broader metabolic changes associated with INSTI use in women.
"The implications of INSTI-associated weight gain are not known," said Amalia Aldredge, M.D., a resident internist at Emory University, who presented the research. "Since we previously observed weight gain in women who switched to INSTIs, the objective of this study was to evaluate the effects of INSTI use on lipid profiles, insulin resistance, and glycemic control in women with HIV."
Aldredge and her colleagues turned to data from the Women's Interagency HIV Study cohort, a prospective study designed to monitor HIV in U.S. women. They compared 182 women who had switched to an INSTI regimen to a group of 699 women who had never switched. About half of the women were black, and their average age was 49 years old.
The switch group experienced significantly greater decreases in HDL cholesterol (-2.6 vs. -0.22 mg/dL, P = .05) and a trend toward greater decreases in total cholesterol, though this did not reach significance. There was no significant difference in LDL cholesterol.
The switch group also saw significantly greater increases in A1c (+0.08% vs. -0.05%, P = .01), but, puzzlingly, this group also trended toward lower incidence of insulin resistance (19% vs. 32%, P = .05).
Aldredge pointed out that her follow-up period was only reached 18 months after the INSTI switch, so longer-term cardiometabolic effects are still unknown.
"This highlights an urgent need for long-term follow-up, especially among women," she said.