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Integrase Strand Transfer Inhibitor–Related Changes in Body Mass Index and Risk of Diabetes: A Prospective Study From the RESPOND Cohort Consortium

Rupasinghe, Dhanushi; Bansi-Matharu, Loveleen; Law, Matthew; Zangerle, Robert; Rauch, Andri; Tarr, Philip E; Greenberg, Lauren; ... Petoumenos, Kathy; + view all (2025) Integrase Strand Transfer Inhibitor–Related Changes in Body Mass Index and Risk of Diabetes: A Prospective Study From the RESPOND Cohort Consortium. Clinical Infectious Diseases , 80 (2) pp. 404-416. 10.1093/cid/ciae406. Green open access

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Abstract

Background: With integrase strand transfer inhibitor (INSTI) use associated with increased body mass index (BMI) and BMI increases associated with higher diabetes mellitus (DM) risk, we explored the relationships between INSTI/non-INSTI regimens, BMI changes, and DM risk. / Methods: RESPOND participants were included if they had CD4, human immunodeficiency virus (HIV) RNA, and ≥2 BMI measurements during follow-up. Those with prior DM were excluded. DM was defined as a random blood glucose ≥11.1 mmol/L, hemoglobin A1c ≥6.5%/48 mmol/mol, use of antidiabetic medication, or site-reported clinical diagnosis. Poisson regression was used to assess the association between natural log (ln) of time-updated BMI and current INSTI/non-INSTI and their interactions on DM risk. / Results: Among 20 865 people with HIV included, most were male (74%) and White (73%). Baseline median age was 45 years (interquartile range [IQR], 37–52), with a median BMI of 24 kg/m2 (IQR, 22–26). There were 785 DM diagnoses with a crude rate of 0.73 (95% confidence interval [CI], .68–.78)/100 person-years of follow-up. ln(BMI) was strongly associated with DM (adjusted incidence rate ratio [aIRR], 16.54 per log increase; 95% CI, 11.33–24.13; P < .001). Current INSTI use was associated with increased DM risk (IRR, 1.58; 95% CI, 1.37–1.82; P < .001) in univariate analyses and only partially attenuated when adjusted for variables including ln(BMI) (aIRR, 1.48; 95% CI, 1.29–1.71; P < .001). There were no interactions between ln(BMI), INSTI, and non-INSTI use and DM (P = .130). / Conclusions: In RESPOND, compared with non-INSTIs, current use of INSTIs was associated with an increased DM risk, which partially attenuated when adjusted for BMI changes and other variables.

Type: Article
Title: Integrase Strand Transfer Inhibitor–Related Changes in Body Mass Index and Risk of Diabetes: A Prospective Study From the RESPOND Cohort Consortium
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1093/cid/ciae406
Publisher version: http://dx.doi.org/10.1093/cid/ciae406
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher's terms and conditions.
Keywords: people living with HIV, INSTI use, BMI, weight gain, diabetes
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute for Global Health
URI: https://discovery.ucl.ac.uk/id/eprint/10196098
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