Darcy A Wooten, MD, MS
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 data claims 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 unable 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.
Darcy A Wooten, MD, MS
Infectious Disease News Editorial Board Member
Associate professor of medicine
Program director, ID fellowship training program
University of California San Diego
Disclosures: Wooten reports no relevant financial disclosures.