Integrase strand transfer inhibitor use linked to higher diabetes risk

Current use of integrase strand transfer inhibitors (INSTIs) vs protease inhibitors or non-nucleotide reverse transcriptase inhibitors is associated with an increased risk for diabetes among people with HIV infection, according to study results published in Clinical Infectious Diseases.

Researchers conducted a study within the RESPOND cohort consortium, a prospective multicohort collaboration, to investigate the associations between INSTI and non-INSTI regimens, changes in BMI, and diabetes risk. Data were sourced from 19 observational cohorts and more than 30,000 people with HIV in Europe and Australia. Adults on dual or triple combination antiretroviral therapy who had CD4, HIV RNA, and at least 2 BMI measurements during follow-up were eligible for inclusion. The primary outcome was incident diabetes, which was defined by laboratory values, use of antidiabetic medication, or clinical diagnosis. Poisson regression was used to assess factors associated with diabetes.

A total of 20,865 people with HIV (median age at baseline, 45 years; men, 74%; White, 73%; Western European, 46%; median BMI at baseline, 23.8 kg/m²) were included in the study, 23% of whom had an HIV viral load of at least 200 copies/mL and 2% of whom were co-infected with hepatitis B or C. Patients with onset diabetes vs the overall study population were older and had a higher median BMI.

At baseline, 25% of patients were on an INSTI-containing regimen, 58% on tenofovir disoproxil fumarate (TDF), and 6% on tenofovir alafenamide (TAF).

During 107,641 person-years (PY) follow-up, there were 785 incident cases of diabetes, which correlated to a crude incidence rate of 0.73 (95% CI, 0.68-0.78) per 100 PY follow-up.

Increased BMI was associated with increased diabetes risk (adjusted incident rate ratio [aIRR], 16.54 per log increase; 95% CI, 11.33-24.13; P <.001). Current INSTI use was also associated with increased risk for diabetes (IRR, 1.58; 95% CI, 1.37-1.82; P <.001), which only slightly attenuated when adjusting for other variables, including BMI (aIRR, 1.48; 95% CI, 1.29-1.71; P <.001). The adjusted absolute risk difference between INSTI and non-INSTI use was 0.29 (95% CI, 0.28-0.29) per 1000 PY follow-up.

The association between BMI and diabetes did not differ according to INSTI/non-INSTI use (P =.130), nor did it differ when assessed by age (P =.811) and sex (P =.325). Current TAF and TDF use were also not associated with diabetes and had similar diabetes risk (aIRR, 1.01; 95% CI, 0.82-1.25; P =.912). Compared with men, women had a lower risk for diabetes (aIRR, 0.69; 95% CI, 0.57-0.85; P <.001). Other factors associated with increased diabetes risk included older age, injecting drug use mode of HIV acquisition, Black or other race, lower CD4 cell counts, and high blood pressure.

Study limitations include the observational nature of BMI assessments, inability to assess other factors that may have influenced BMI, and potential underdiagnosis of diabetes.

“This suggests that BMI increases on INSTIs are associated with increase in the risk of DM by a similar amount as BMI increases for other reasons and would support interpreting INSTI-related BMI increases in terms of DM risk in a similar way to other BMI increases,” the researchers concluded.

Disclosure: This research was supported by ViiV Healthcare LLC, Gilead Sciences, and Merck Sharp & Dohme. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.

By Lisa Kuhns, PhD

References:

Rupasinghe D, Bansi-Matharu L, Law M, et al. Integrase strand transfer inhibitor (INSTI) related changes in BMI and risk of diabetes: a prospective study from the RESPOND cohort consortium. Clin Infect Dis. Published online August 9, 2024. doi:10.1093/cid/ciae406