Title

Integrase strand inhibitors (INSTI) related changes in BMI and risk of diabetes

Presenter

Dhanushi Rupasinghe

Authors

D. Rupasinghe¹, K. Petoumenos¹, B. Neesgaard², E. Florence³, J. Begovac⁴, A. Rauch⁵, P. Tarr⁵, R. Zangerle⁶, F. Wit⁷, A. d'Arminio Monforte⁸, C. Mussini⁹, A. Sönnerborg¹⁰, M. Stecher¹¹, V. Brandes¹¹, S. De Wit¹², E. Fontas¹³, N. Chkhartishvili¹⁴, A. Groh¹⁵, N. Jaschinski², L. Greenberg², L.B. Matharu¹⁶, A.A. Volny¹⁷, C. Cohen¹⁸, V. Vannappagari¹⁹, L. Young²⁰, L. Ryom², M. Law¹

Institutions

¹The Australian HIV Observational Database (AHOD), Kirby Institute, Biostatistics and Databases Program, Unsw Sydney, Australia, ²CHIP, Department of Infectious Diseases, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark, ³Institute of Tropical Medicine, Antwerp, Belgium, ⁴Reference Center for Diagnostics and Treatment of HIV-infection, University Hospital for Infectious Diseases, Zagreb, Croatia, ⁵Swiss HIV Cohort Study (SHCS), University of Zurich, Zurich, Switzerland, ⁶Austrian HIV Cohort Study (AHIVCOS), Medizinische Universität Innsbruck, Innsbruck, Austria, ⁷AIDS Therapy Evaluation in the Netherlands (ATHENA) Cohort, HIV Monitoring Foundation, Amsterdam, Netherlands, ⁸Italian Cohort Naive Antiretrovirals (ICONA), ASST Santi Paolo e Carlo, Milano, Italy, ⁹Modena HIV Cohort, Università degli Studi di Modena, Modena, Italy, ¹⁰Swedish InfCare HIV Cohort, Karolinska University Hospital, Stockholm, Sweden, ¹¹University Hospital Cologne, Cologne, Germany, ¹²CHU Saint-Pierre, Centre de Recherche en Maladies Infectieuses a.s.b.l., Brussels, Belgium, ¹³Nice HIV Cohort, Université Côte d’Azur et Centre Hospitalier Universitaire, Nice, France, ¹⁴Georgian National AIDS Health Information System (AIDS HIS), Infectious Diseases, AIDS and Clinical Immunology Research Center, Tbilisi, Georgia, ¹⁵Frankfurt HIV Cohort Study, Johann Wolfgang Goethe-University Hospital, Frankfurt, Germany, ¹⁶Centre for Clinical Research, Epidemiology, Modelling and Evaluation (CREME), Institute for Global Health, University College London, London, United Kingdom, ¹⁷European AIDS Treatment Group, Brussels, Belgium, ¹⁸Gilead, Foster City, United States, ¹⁹ViiV, Chapel Hill, United States, ²⁰MSD, Rahway, United States

BACKGROUND: Integrase strand inhibitor (INSTI) use in people living with HIV (PLWH) has been associated with increased body mass index (BMI). BMI increases have also been associated with a higher risk of diabetes (DM). This study explored the relationship between INSTI and non-INSTI regimens use, BMI changes, and the risk of DM.
METHODS: RESPOND participants were included if they had CD4, HIV RNA, and multiple BMI measurements. Those with prior DM, and pregnant women, were excluded. DM was defined as a random blood glucose>11.1 mmol/L, HbA1c>6.5%/48 mmol/mol, use of antidiabetic medication or clinical diagnosis. Poisson regression assessed the association between time updated log BMI, current INSTI/non-INSTI and TDF/TAF use, and their interactions, on DM risk.
RESULTS: 20,865 PLHIV were included, most were male (74%) and white ethnicity (73%). The median age was 45 years (IQR 37–52) with a median BMI of 24 kg/m² (IQR 22-26). Over 107,641 PYFU, there were 785 DM diagnoses, a crude rate of 0.73 (CI 0.68 – 0.78) /100 person years. Log BMI was strongly associated with DM (aIRR 18.2 per log increase, 95% CI 11.7, 28.3; p<0.001). In univariate analyses, current INSTI use was associated with increased risk of diabetes (IRR 1.58, 95% CI 1.37, 1.82; p<0.001). This was partially attenuated when adjusted for time updated log BMI and other variables (aIRR 1.48, 95% CI 1.28, 1.72; p<0.001) (Figure 1). In adjusted analyses current TAF use had similar DM risk to current TDF (aIRR=0.98, 95%CI 0.79-1.20, p=0.818). There was little evidence of an interaction between log BMI, INSTI and non-INSTI use, and DM (p=0.130).

CONCLUSIONS: In RESPOND, current use of INSTIs vs. non-INSTI was associated with an increased risk of diabetes which partially attenuated when adjusted for BMI changes and other variables. There was no difference in DM risk between current TAF and TDF users.

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