Diabetes Mellitus in persons with Human Immunodeficiency Virus naïve to antiretroviral therapy starting Integrase Inhibitors

Abstract

Background: Integrase Strand Transfer Inhibitors (INSTIs), globally used as first-line therapy in patients with HIV antiretroviral therapy (ART)-naïve, are associated with weight gain. Considering the potential association of weight gain and metabolic complications, this study aims to determine the impact of INSTIs on diabetes mellitus (DM) onset and cardiometabolic parameters. Methods: We performed a retrospective cohort study in HIV-infected persons, naïve to ART, and initiating INSTI-based regimens, between January 2011 and January 2023. Data was collected at different times for 9 years. The primary outcome was to determine the incidence of DM. The secondary outcomes were to evaluate the association between the onset of DM with weight gain and other cardiometabolic parameters; and to establish predictors of DM. The Kaplan-Meier method and Cox regression adjusted for age, CD4 T-cell count and body mass index (BMI) at baseline were performed. Results: Of a total of 352 patients included in our study, 30 patients developed DM with an incidence rate of 24.6/1000 person-years (PY). We found a significant association of DM with older age, lower education level, higher BMI, lower CD4 T-cell count, more advanced HIV stage, non dolutegravir (DTG)-based INSTI regimen, and hepatitis B and C coinfection. The greater median change in fasting blood glucose occurred at 3 years of follow-up. The cumulative incidence of DM was 6.7% within the first three years of follow-up, achieving 11.7% at 5 years. Patients receiving a DTG-based regimen had a lower incidence of DM compared to other INSTIs. Cox regression concluded that older age (adjusted hazard ratio (aHR) 1.07; 95% IC 1.03-1.12; p<0.001) and higher BMI (aHR 1.15; 95% IC 1.04-1.34; p=0.008) are independent predictors of DM. Conclusions: INSTIs seem to be associated with an elevated incidence of DM, highlighting the importance of glycaemic vigilance in patients with HIV starting INSTI, specifically in older ones and with an elevated BMI.