Diabetes risk increased among people with HIV on INSTI-based ART
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People with HIV who are on ART regimens using integrase strand transfer inhibitors are at an increased risk for diabetes or hyperglycemia within the first 6 months of treatment, researchers found.
“We had noted in clinic that a handful of patients who started integrase strand transfer inhibitors (INSTIs) developed diabetes or lost control of previously well-controlled diabetes,” Jane A. O’Halloran, MD, PhD, assistant professor of medicine at the Washington University School of Medicine in St. Louis, told Healio. “This, coupled with evidence that INSTIs are associated with other metabolic complications, prompted the study.”
O’Halloran and colleagues used insurance databases to identify adults with HIV who had newly initiated ART between July 1, 2007, and June 30, 2018, and assessed them for new-onset diabetes or hyperglycemia in the 6 months following their treatment initiation.
Among the 42,382 participants included in the study, 54% were treated with INSTI-based regimens. O’Halloran and colleagues reported that these patients were 31% more likely to develop new-onset diabetes or hyperglycemia (HR = 1.31; 95% CI, 1.15-1.48) compared with participants who initiated non-INSTI based regimens.
Elvitegravir (adjusted HR = 1.54; 95% CI, 1.32-1.97; P < .001) was associated with the highest risk and raltegravir (aHR = 1.19; 95% CI, 0.95-1.03, 1.37; P = .02) the lowest, the researchers found.
“We need to continue to monitor people receiving ART for metabolic toxicities as these side effects are not only associated with older ART but can sometimes occur with contemporary ART,” O’Halloran said. “In addition, for people living with HIV who present with new-onset diabetes, we should consider if they are on INSTI-based treatment and if this could be contributing.”
Perspective
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The association between INSTIs and weight gain among people with HIV is well established. Newer studies are beginning to explore the metabolic implications associated with INSTIs.
Although the study by O’Halloran and colleagues has several strengths, including a large sample size and several sensitivity analyses, there are some important limitations. Because claims data were used, individual patient data such as weight gain and baseline CD4 cell count could not be obtained. Lack of weight gain data prevents us from determining whether the incident diabetes and hyperglycemia were due to direct effects of INSTIs or weight gain associated with INSTIs, or both. Additionally, patients with very low baseline CD4 cell counts often experience a “return-to-health” phenomenon after ART initiation and we are not able to determine what role this effect may have played in this study.
Another limitation is that patients who were started on INSTIs had significantly higher rates of obesity diagnoses at baseline compared with the non-INSTI group and thus may have represented a population more susceptible to hyperglycemia after ART initiation. Finally, the study looked only at outcomes 6 months after ART initiation. It is unclear if this effect plateaus, regresses or progresses over time.
Despite these limitations, the results of this study are important and concerning, especially given the association of INSTIs and weight gain, as well as the obesity epidemic in this country. Additional studies to further elucidate the impact of INSTIs on metabolic complications like diabetes and hyperglycemia are required.
At the bedside, clinicians should consider intensifying their counseling about weight gain and metabolic complications when starting INSTIs and potentially enhance efforts to counsel patients and facilitate their ability to make lifestyle modifications in their diet and exercise. INSTIs remain first-line agents for treatment-naive patients, given their efficacy and tolerability. However, it is important for us to engage patients in discussions about these nuances.
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