Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2025 Feb 24;80(2):404-416.
doi: 10.1093/cid/ciae406.

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

Dhanushi Rupasinghe  1 , Loveleen Bansi-Matharu  2 , Matthew Law  1 , Robert Zangerle  3 , Andri Rauch  4 , Philip E Tarr  5 , Lauren Greenberg  2 , Bastian Neesgaard  6 , Nadine Jaschinski  6 , Stéphane De Wit  7 , Ferdinand Wit  8 , Antonella d'Arminio Monforte  9 , Eric Fontas  10 , Antonella Castagna  11 , Melanie Stecher  12 , Eric Florence  13   14 , Josip Begovac  15 , Cristina Mussini  16 , Anders Sönnerborg  17 , Akaki Abutidze  18 , Ana Groh  19 , Vani Vannappagari  20 , Cal Cohen  21 , Lital Young  22 , Sean Hosein  23 , Lene Ryom  6   24   25 , Kathy Petoumenos  1
Affiliations

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

Dhanushi Rupasinghe et al. Clin Infect Dis. .

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.

Keywords: BMI; INSTI use; diabetes; people with HIV; weight gain.

PubMed Disclaimer

Conflict of interest statement

Potential conflicts of interest. V. V., C. C., and L. Y. are employees of ViiV Healthcare, Gilead Sciences, and MSD, respectively. A. R. reports support to his institution for advisory boards and/or travel grants from MSD, Gilead Sciences, Pfizer, and Moderna and an investigator initiated trial grant from Gilead Sciences; all remuneration went to his home institution, not to A. R. personally, and all remuneration was provided outside the submitted work. P. E. T.'s institution reports grants and other fees from Gilead Sciences, Merck, and ViiV, outside the submitted work. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.

Figures

Figure 1.
Figure 1.
Study population. Abbreviations: ART, antiretroviral therapy; ARV, antiretroviral; BMI, body mass index; cART, combination antiretroviral therapy.
Figure 2.
Figure 2.
A, Predicted risk of diabetes mellitus (DM) by current INSTI use and BMI. The predicted risk per 1000 person-years of DM for BMI among INSTI and non-INSTI users when adjusted for sex, natural log of age, human immunodeficiency virus risk group, ethnicity, CD4 cell counts, blood pressure, current tenofovir disoproxil fumarate/tenofovir alafenamide use. Among INSTI users, 12% were on raltegravir, 60% on dolutegravir, and 28% on other INSTIs (cobicistat-boosted elvitegravir, bictegravir, and cabotegravir). B, Kaplan–Meier plot demonstrating the time to DM event from the start of drug class. Abbreviations: BMI, body mass index; INSTI, integrase strand transfer inhibitor; NNRTI, non-nucleoside reverse transcriptase inhibitor; PI, protease inhibitor.
See this image and copyright information in PMC

References

    1. World Health Organization Press . Updated recommendations on first-line and second-line antiretroviral regimens and post-exposure prophylaxis and recommendations on early infant diagnosis of HIV. 2018:79. Available at: https://www.who.int/publications/i/item/WHO-CDS-HIV-18.51. Accessed 15 January 2023.
    1. Neesgaard B, Mocroft A, Zangerle R, et al. Virologic and immunologic outcomes of treatment with integrase inhibitors in a real-world setting: the RESPOND cohort consortium. PLoS One 2020; 15:e0243625. - PMC - PubMed
    1. Herrin M, Tate JP, Akgun KM, et al. Weight gain and incident diabetes among HIV-infected veterans initiating antiretroviral therapy compared with uninfected individuals. J Acquir Immune Defic Syndr 2016; 73:228–36. - PMC - PubMed
    1. Bakal DR, Coelho LE, Luz PM, et al. Obesity following ART initiation is common and influenced by both traditional and HIV-/ART-specific risk factors. J Antimicrob Chemother 2018; 73:2177–85. - PMC - PubMed
    1. Taramasso L, Ricci E, Menzaghi B, et al. Weight gain: a possible side effect of all antiretrovirals. Open Forum Infect Dis 2017; 4:ofx239. - PMC - PubMed

Publication types

Substances