Increased Diabetes Risk Linked to INSTI Use in HIV Patients, Highlights study

The prospective study from the RESPOND cohort consortium has revealed concerning findings regarding the use of integrase strand transfer inhibitors in individuals living with HIV. The research indicates that current usage of INSTIs is associated with an increased risk of developing diabetes, a link that appears to be influenced by changes in body mass index (BMI) and other factors.

Given that the use of integrase strand transfer inhibitors is linked to increased BMI and that BMI increases are associated with a higher risk of diabetes mellitus (DM), Dhanushi Rupasinghe, The Australian HIV Observational Database (AHOD), The Kirby Institute, UNSW Sydney, Australia, and colleagues investigated the relationship between INSTI and non-INSTI regimens, changes in BMI, and the risk of developing DM.

To investigate this relationship, the researchers included RESPOND participants who had CD4 counts, HIV RNA levels, and at least two BMI measurements during follow-up. Individuals with a history of diabetes mellitus were excluded. DM was defined based on a random blood glucose level of ≥ 11.1 mmol/L, an HbA1c of ≥ 6.5% (48 mmol/mol), the use of antidiabetic medications, or a clinical diagnosis reported by the site.

The researchers utilized Poisson regression to evaluate the association between the natural logarithm (ln) of time-updated BMI, current use of INSTI versus non-INSTI regimens, and their interactions concerning the risk of developing DM.

The following were the key findings of the study:

• Among 20,865 people with HIV included, most were male (74%) and White (73%). The baseline median age was 45 years with a median BMI of 24 kg/m2.
• There were 785 DM diagnoses with a crude rate of 0·73/100 PYFU.
• Ln(BMI) was strongly associated with DM (adjusted incidence rate ratio (aIRR) 16·54 per log increase).
• Current INSTI use is associated with increased DM risk (IRR 1·58) in univariate analyses, only partially attenuated when adjusted for variables including ln(BMI) (aIRR 1·48).
• There was no interaction between ln(BMI), INSTI and non-INSTI use, and DM.

Study limitations include the observational design of BMI assessments, the inability to account for other factors that may have influenced BMI, and the potential for underdiagnosing diabetes.

In the RESPOND study, the current use of INSTIs was linked to a higher risk of diabetes than non-INSTIs; however, this association was somewhat diminished when accounting for changes in BMI and other factors.

The researchers concluded, "The findings indicate that increases in BMI associated with INSTI use are linked to a similar rise in the risk of diabetes as BMI increases from other causes. Therefore, it would be prudent to interpret INSTI-related BMI changes in the context of diabetes risk similarly to other BMI increases."

Reference:

Rupasinghe, D., Law, M., Zangerle, R., Rauch, A., Tarr, P. E., Greenberg, L., Neesgaard, B., Jaschinski, N., De Wit, S., Wit, F., Monforte, A. D., Fontas, E., Castagna, A., Stecher, M., Brandes, V., Florence, E., Begovac, J., Mussini, C., Sönnerborg, A., . . . Petoumenos, K. Integrase strand transfer inhibitor (INSTI) related changes in BMI and risk of diabetes: A prospective study from the RESPOND cohort consortium. Clinical Infectious Diseases. https://doi.org/10.1093/cid/ciae406