Women Show Higher INSTI-Associated Weight Gain and Incident Diabetes Mellitus Than Men

Study authors investigated whether integrase strand transfer inhibitor treatment was associated with increased weight change from baseline and incident diabetes mellitus.

Compared with men and patients with HIV not receiving integrase strand transfer inhibitors (INSTIs), women are more susceptible to INSTI-associated weight gain, according to a study results presented at IDWeek, held virtually from October 21 to 25, 2020.

An emerging issue associated with INSTI antiretrovirals is excessive weight gain. There is also a known association between excess weight and impaired glucose tolerance; however, the metabolic implications of INSTI-associated weight gain have not been established. Therefore, in the current study, researchers evaluated the prevalence of INSTI-associated weight gain among a diverse, urban population, and investigated potential risk factors and metabolic implications.

Of the 612 patients included in the study, 123 were initiated with INSTIs and 489 with alternative anchor regimens (non-INSTIs). Patients with a diabetes mellitus (DM) prescription before antiretroviral therapy (ART) initiation were excluded. Researchers compared patients who were initiated with INSTIs with those with an alternative regimen who remained on their initial regimen for at least 18 months. In total, 237 patients (38.7%) were women, had an average age of 41.56 years, and an average body mass index (BMI) of 25.55 (range, 22.9-28.9); 339 patients (55.4%) were Black/African American.

The primary outcome of the study was percent weight change in the first 24 months of ART. The secondary outcome was incident DM diagnosis in the 19 months after ART using progression-free survival.

Results suggested that women were more susceptible to INSTI-associated weight gain. The INSTI vs non-INSTI cohort experienced a higher percent weight gain in the first 24 months post-ART initiation. Furthermore, women vs men in the INSTI cohort experienced a higher percent weight gain in the first 24 months (+9.57%; P =.002).

The adjusted multivariable analysis of 24-month weight gain due to INSTIs showed a weight gain of 1.68% (95% CI, -3.88% to 7.24%) in White men, 2.08% (-2.52% to 6.68%) in non-White men, 10.62% (2.83%-18.41%) in White women, and 11.02% (5.17-16.88) in non-White women.

Compared to non-INSTI regimens, the use of INSTIs was also associated with more incident DM diagnoses in the first 18 months of ART (hazard ratio, 3.27; P =.014).

Women having “higher INSTI-associated weight gain suggests they may be more susceptible to adverse metabolic issues,” the researchers concluded.

Disclosure: Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.


Asundi A, Olson A, Jiang W, et al. Risk factors and metabolic implications of integrase inhibitor associated weight gain. Presented at: IDWeek 2020; October 21-25, 2020. Poster 946.