HIV Treatment With INSTI-Based Antiretroviral Therapy Increases Risk for Diabetes, Hyperglycemia

Investigators assessed the risk for incident diabetes and hyperglycemia among patients with HIV infection receiving integrase strand transfer inhibitors.

Integrase strand transfer inhibitors (INSTIs) were associated with an increased risk for new-onset diabetes mellitus and hyperglycemia among patients with HIV infection, according to results of a study published in Clinical Infectious Diseases.

Investigators at Washington University School of Medicine sourced data for this study from the IBMÒ MarketScanÒ Commercial Database and Medicaid Multi-State Database. They assessed the incident risk for diabetes and hyperglycemia among patients (N=42,382) with HIV infection who initiated antiretroviral therapy (ART) between 2007 and 2019. The composite primary outcome was new-onset diabetes and hyperglycemia within 6 months of ART initiation.

This study comprised patients receiving INSTI-based ART regimens (n=22,762) and nonINSTI-based regimens (n=19,620). Among patients in the INSTI and nonINSTI groups, the mean age was 37.1 and 39.6 years (P <.001), 73.0% and 74.3% were men (P =.002), and 4.69% and 2.23% had a BMI indicating obesity (P <.001), respectively.

Of patients in the INSTI group, treatments included raltegravir in 39.5%, elvitegravir in 28.1%, dolutegravir in 26.7%, and bictegravir in 5.7%. Of note, the number of patients who received each of these specific medications increased over time.

In the 6 months following ART initiation, diabetes and hyperglycemia was diagnosed among 521 (2.3%) patients in the INSTI group and 361 (1.8%) of those in the nonINSTI group.

The investigators found that patients receiving INSTI-based ART had a 31% increased risk for incident diabetes mellitus and hyperglycemia (hazard ratio [HR], 1.31; 95% CI, 1.15-1.48). Stratification by specific INSTI medications showed that elvitegravir (HR, 1.54; 95% CI, 1.32-1.79), dolutegravir (HR, 1.26; 95% CI, 1.03-1.55), and raltegravir (HR, 1.19; 95% CI, 1.03-1.37) also were associated with an increased risk for diabetes and hyperglycemia. Of note, bictegravir was not associated with an increased risk for either disease (HR, 1.45; 95% CI, 0.84-2.51; P =.182).

Similar findings were observed in a sensitivity analysis that assessed the addition of tenofovir alafenamide among patients receiving INSTI-based ART.

This study may have been limited by potential confounding and the relatively small number of patients in the INSTI group who were receiving bictegravir.

According to the investigators, “these results add to a growing body of evidence [that] suggests INSTIs may impact glycemic control.” Additional studies are needed to evaluate the metabolic toxicities associated with these treatments.

Disclosure: Multiple authors declared affiliations with industry. Please see the original reference for a full list of disclosures.


O’Halloran JA, Sahrmann J, Parra-Rodriguez L, et al. Integrase strand transfer inhibitors are associated with incident diabetes mellitus in people with HIV. Clin Infect Dis. 2022;ciac355. doi:10.1093/cid/ciac355