Integrase Strand Transfer Inhibitors Are Associated With Incident Diabetes Mellitus in People With Human Immunodeficiency Virus
- PMID: 35521785
- PMCID: PMC10200297
- DOI: 10.1093/cid/ciac355
Integrase Strand Transfer Inhibitors Are Associated With Incident Diabetes Mellitus in People With Human Immunodeficiency Virus
Abstract
Background: Integrase strand transfer inhibitors (INSTIs) are associated with weight gain in people with HIV (PWH). Less is known about the risk of other metabolic outcomes such as diabetes mellitus and hyperglycemia.
Methods: IBM® MarketScan® databases for commercially and Medicaid-insured adults were used to identify PWH newly initiating antiretroviral therapy (ART). The primary outcome was a composite of new-onset diabetes mellitus/hyperglycemia in the 6 months following ART initiation and was identified using International Classification of Disease, Ninth revision, Clinical Modification (ICD-9-CM) and ICD-10-CM diagnosis and procedure codes and Current Procedural Terminology, 4th Edition (CPT-4) codes. To examine the relationship between INSTI use and the composite outcome, we estimated the risk using Cox proportional hazards models with calendar time-specific standardized mortality ratio weights.
Results: Of 42 382 PWH who initiated ART between 1 July 2007 and 30 June 2018, 22 762 (54%) were treated with INSTI-based regimens. Mean age was 38 years, 74% were male, and 19% were Medicaid insured. PWH on INSTIs were 31% more likely to develop new-onset diabetes mellitus/hyperglycemia (hazard ratio [HR], 1.31; 95% confidence interval [CI], 1.15-1.48]) compared with those who initiated non-INSTI-based regimens. When examined individually, the highest risk was associated with elvitegravir (HR, 1.54; 95% CI, 1.32-1.97; P < .001) and the lowest risk with raltegravir (HR, 1.19; 95% CI, 1.03-1.37; P = .02).
Conclusions: INSTI use was associated with increased risk of new-onset diabetes mellitus/hyperglycemia in the 6 months following ART initiation.
Keywords: HIV; antiretroviral therapy; diabetes; hyperglycemia; integrase strand transfer inhibitors.
© The Author(s) 2022. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
Conflict of interest statement
Potential conflicts of interest . J. A. O. reports grants from Janssen. A. M. B. reports grants from Merck & Co. M. A. O. reports grants and personal fees from Pfizer. W. G. P. reports grants and personal fees from Merck & Co. 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


Similar articles
-
Incidence of cardiometabolic outcomes among people living with HIV-1 initiated on integrase strand transfer inhibitor versus non-integrase strand transfer inhibitor antiretroviral therapies: a retrospective analysis of insurance claims in the United States.J Int AIDS Soc. 2023 Jun;26(6):e26123. doi: 10.1002/jia2.26123. J Int AIDS Soc. 2023. PMID: 37306118 Free PMC article.
-
Weight gain among treatment-naïve persons with HIV starting integrase inhibitors compared to non-nucleoside reverse transcriptase inhibitors or protease inhibitors in a large observational cohort in the United States and Canada.J Int AIDS Soc. 2020 Apr;23(4):e25484. doi: 10.1002/jia2.25484. J Int AIDS Soc. 2020. PMID: 32294337 Free PMC article.
-
Integrase Inhibitor Use Associated with Weight Gain in Women and Incident Diabetes Mellitus.AIDS Res Hum Retroviruses. 2022 Mar;38(3):208-215. doi: 10.1089/AID.2021.0091. Epub 2022 Jan 10. AIDS Res Hum Retroviruses. 2022. PMID: 34877881 Free PMC article.
-
Review of integrase strand transfer inhibitors for the treatment of human immunodeficiency virus infection.Expert Rev Anti Infect Ther. 2015;13(10):1195-212. doi: 10.1586/14787210.2015.1075393. Epub 2015 Aug 9. Expert Rev Anti Infect Ther. 2015. PMID: 26293294 Review.
-
A clinical review of HIV integrase strand transfer inhibitors (INSTIs) for the prevention and treatment of HIV-1 infection.Retrovirology. 2022 Oct 22;19(1):22. doi: 10.1186/s12977-022-00608-1. Retrovirology. 2022. PMID: 36273165 Free PMC article. Review.
Cited by
-
Effect of a Supervised Aerobic Exercise Training Program and Ginkgo Biloba Extract on Metabolic Parameters and Functional Capacity in HIV-Infected Subjects.Healthcare (Basel). 2025 Mar 18;13(6):663. doi: 10.3390/healthcare13060663. Healthcare (Basel). 2025. PMID: 40150513 Free PMC article.
-
Outcomes of switching from protease inhibitor-based antiretroviral therapy to bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) in virologically suppressed adults with nucleos(t)ide analogue resistance- a phase IV randomised, open-label study (PIBIK study).Virol J. 2025 Feb 10;22(1):33. doi: 10.1186/s12985-025-02648-3. Virol J. 2025. PMID: 39930490 Free PMC article. Clinical Trial.
-
Diabetes in HIV: the Link to Weight Gain.Curr HIV/AIDS Rep. 2023 Feb;20(1):9-18. doi: 10.1007/s11904-022-00642-w. Epub 2022 Nov 23. Curr HIV/AIDS Rep. 2023. PMID: 36418528 Free PMC article. Review.
-
Optimizing Type 2 Diabetes Management in a Medically Complex Patient: A Case Report of a Patient with Type 2 Diabetes and HIV.Diabetes Metab Syndr Obes. 2023 Aug 11;16:2401-2406. doi: 10.2147/DMSO.S415949. eCollection 2023. Diabetes Metab Syndr Obes. 2023. PMID: 37588513 Free PMC article.
-
An update on drug-drug interactions in older adults living with human immunodeficiency virus (HIV).Expert Rev Clin Pharmacol. 2024 Jul;17(7):589-614. doi: 10.1080/17512433.2024.2350968. Epub 2024 Jun 30. Expert Rev Clin Pharmacol. 2024. PMID: 38753455 Free PMC article. Review.
References
-
- Venter WDF, Moorhouse M, Sokhela S, et al. . Dolutegravir plus two different prodrugs of tenofovir to treat HIV. N Engl J Med 2019; 381(9):803–15. - PubMed