Exploring the Relationship Between Dolutegravir and Diabetes Using Routine Data of Patients on Anti-Retroviral Treatment in a High HIV Prevalence Setting
Main Article Content
Abstract
Background: Dolutegravir has been associated with excessive weight gain and type 2 diabetes mellitus (T2DM) The study aimed to describe the incidence and prevalence of type 2 diabetes mellitus in a cohort of patients exposed and non-exposed to dolutegravir containing antiretroviral therapy in Eswatini.
Methods: We conducted a retrospective observational study using routinely collected data from electronic medical records for adults aged ≥25years active on antiretroviral therapy in two of the country’s regions between 01 October 2018 and 31 August 2025. Included patients were adults (≥25 years) active on antiretroviral therapy with no prior diagnosis of diabetes mellitus. The primary outcome was a documented diagnosis of type 2 diabetes mellitus among dolutegravir initiators- patients who started antiretroviral therapy on a dolutegravir-based regimen; dolutegravir transitioners- patients previously on a non-dolutegravir regimen who transitioned to a dolutegravir-based regimen; and non-dolutegravir users- patients that were never exposed to dolutegravir. Multiple imputation was used to handle missing data in body mass index and antiretroviral therapy duration. Descriptive statistics were used to describe patient characteristics, and Poisson log link regression was used to compute incidence risk ratios.
Results: A total of 102330 patients were analyzed (21938 in dolutegravir initiators group, 73967 in dolutegravir transitioners group and 6425 in non-dolutegravir users group). The participant mean age was 43.7±11.7years, the mean duration on antiretroviral therapy was 9.4±3.9years and mean body mass index (BMI) was 27.5±6.2 kg/m2. The overall prevalence of type 2 diabetes was 2.0% (1.2% among dolutegravir initiators; 2.3% among dolutegravir transitioners and 1.4% among non-dolutegravir users) and the overall incidence rate was 3.6 cases per 1000person-years [Non-dolutegravir Users-6.2 per 1000person-years), Dolutegravir Transitioners (3.6 per 1000person-years) and Dolutegravir Initiators (2.9 per 1000person-years)]. After adjusting for age, BMI, and duration on antiretroviral therapy, Dolutegravir Initiators (aIRR=0.4) and Dolutegravir Transitioners (aIRR=0.4) had a lower risk than Non-Dolutegravir Users.
Conclusion: There was a protective relationship for developing type 2 diabetes mellitus for patients on dolutegravir-based regimens in comparison to non-dolutegravir regimens. All patients commencing antiretroviral therapy should have baseline and ongoing blood glucose monitoring as a critical component in the management of HIV.
Keywords:
Type 2 Diabetes Mellitus, People living with HIV, antiretroviral treatment, dolutegravir-based regimens, high HIV prevalence setting
Article Details
How to Cite
HAUMBA, Samson et al.
Exploring the Relationship Between Dolutegravir and Diabetes Using Routine Data of Patients on Anti-Retroviral Treatment in a High HIV Prevalence Setting.
Medical Research Archives, [S.l.], v. 14, n. 2, feb. 2026.
ISSN 2375-1924.
Available at: <https://esmed.org/MRA/mra/article/view/7309>. Date accessed: 02 mar. 2026.
doi: https://doi.org/10.18103/mra.v14i2.7309.
Section
Research Articles
The Medical Research Archives grants authors the right to publish and reproduce the unrevised contribution in whole or in part at any time and in any form for any scholarly non-commercial purpose with the condition that all publications of the contribution include a full citation to the journal as published by the Medical Research Archives.
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3. Ndona M, Longo-Mbenza B, Umba B, et al. Nadir CD4+ religion antiretroviral therapy incidence of type 2 T2DM mellitus and increasing rates of obesity among black Africans with HIV disease. Int J Gen Med. 2012;5:983-990. doi:10.2147/IJGM.S34666
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8. Yudkin JS. Adipose tissue, insulin action and vascular disease: inflammatory signals. Int J Obes Relat Metab Disord. 2003;27(suppl 3):S25-S28. doi:10.1038/sj.ijo.0802496
9. Abera MA, Tequare MH, Berhe E, et al. Dolutegravir-associated hyperglycemia in people living with human immune-deficiency virus: a prospective cohort study. Research Square. Preprint posted online February 23, 2022. doi:10.21203/rs.3.rs-1396874/v1
10. Calza L, Colangeli V, Magistrelli E, et al. Prevalence of metabolic syndrome in HIV-infected naive to antiretroviral therapy or receiving first-line treatment. HIV Clin Trials. 2017;18(3):110-117. doi:10.1080/15284336.2017.1311502
11. Odenyo JA. Prevalence of Dolutegravir Associated Hyperglycemia and Its Covariates Among Persons Living with HIV on Treatment at Kenyatta National Hospital. Thesis. University of Nairobi; 2020.
12. Hirigo AT, Gutema S, Eifa A, Kutema W. Experience of dolutegravir-based antiretroviral treatment and risks of T2DM mellitus. SAGE Open Med Case Rep. 2022;10:2050313X221079444. doi:10.1177/2050313X221079444
13. Hailu W, Tesfaye T, Tadesse A. Hyperglycemia after dolutegravir-based antiretroviral therapy. Int Med Case Rep J. 2021;14:503-507 doi:10.2147/IMCRJ.S323233
14. Dunga A, Magongo S, Nhlabatsi S, et al. An evaluation of post marketing reports of hyperglycemia associated with dolutegravir for treatment of HIV in Eswatini. AIDS Res Ther. 2022;19(1):54. doi:10.1186/s12981-022-00481-0
15. Sullivan AK, Feher MD, Nelson MR, Gazzard BG. Marked hypertriglyceridaemia associated with ritonavir therapy. AIDS. 1998;12(11):1393-1394.
16. World Health Organization. Update of Recommendations on First- and Second-line Antiretroviral Regimens: Policy Brief. World Health Organization; 2019. WHO/CDS/HIV/19.15.
17. Twimukye A, Laker M, Odongpiny EAL, et al. Patient experiences of switching from efavirenz- to dolutegravir-based antiretroviral therapy: a qualitative study in Uganda. BMC Infect Dis. 2021;21(1):1154. doi:10.1186/s12879-021-06851-9
18. Zakumumpa H, Kiguba R, Ndagije HB, et al. Patient experiences of sexual dysfunction after transition to dolutegravir-based HIV treatment in mid-western Uganda: a qualitative study. BMC Infect Dis. 2022;22(1):692. doi:10.1186/s12879-022-07673-z
19. Bastard JP, Caron M, Vidal H, et al. Association between altered expression of adipogenic factor SREBP1 in lipoatrophic adipose tissue from HIV-1-infected patients and abnormal adipocyte differentiation and insulin resistance. Lancet. 2002;359(9311):1026-1031. doi:10.1016/S0140-6736(02)08094-1
20. Bourgi K, Jenkins CA, Rebeiro PF, et al. 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;23(4):e25484. doi:10.1002/jia2.25484
21. Hsu R, Brunet L, Mounzer KC, et al. Characterizations of weight gain following antiretroviral regimen initiation in treatment-naïve individuals living with HIV. Paper presented at: 17th European AIDS Conference; November 6-9, 2019; Basel, Switzerland.
22. Bourgi K, Rebeiro PF, Turner M, et al. Greater weight gain in treatment-naive persons starting dolutegravir-based antiretroviral therapy. Clin Infect Dis. 2020;70(7):1267-1274. doi:10.1093/cid/ciz407
23. Ruderman S, Nance RM, Whitney B, et al. Dolutegravir-based regimens are associated with weight gain over two years following ART-initiation in ART-naïve people living with HIV (PLWH). Paper presented at: 17th European AIDS Conference; November 6-9, 2019; Basel, Switzerland.
24. World Health Organization. Updated Recommendations on First-line and Second-line Antiretroviral Regimens and Post-exposure Prophylaxis and Recommendations on Early Infant Diagnosis of HIV. World Health Organization; 2020.
25. Taramasso L, Tatarelli P, Ricci E, et al. Improvement of lipid profile after switching from efavirenz or ritonavir-boosted protease inhibitors to rilpivirine or once-daily integrase inhibitors: results from a large observational cohort study (SCOLTA). BMC Infect Dis. 2018;18(1):357. doi:10.1186/s12879-018-3268-y
26. Swindells S, Andrade-Villanueva JF, Richmond GJ, et al. Long-acting cabotegravir and rilpivirine for maintenance of HIV-1 suppression. N Engl J Med. 2020;382(12):1112-1123. doi:10.1056/NEJMoa1904398
27. Pilkington V, Hughes SL, Pepperrell T, et al. Tenofovir alafenamide vs tenofovir disoproxil fumarate: an updated meta-analysis of 14,894 patients across 14 trials. AIDS. 2020;34(15):2259-2268. doi:10.1097/QAD.0000000000002681
28. Namara D, Schwartz JI, Tusubira AK, et al. The risk of hyperglycemia associated with use of dolutegravir among adults living with HIV in Kampala, Uganda: a case-control study. Int J STD AIDS. 2022;33(14):1158-1164. doi:10.1177/09564624221129410
29. Cheng X, Yu X, Ding YJ, et al. The th17/Treg imbalance in patients with acute coronary syndrome. Clin Immunol. 2008;127(1):89-97. doi:10.1016/j.clim.2008.01.009
30. Patel DN, King CA, Bailey SR, et al. Interleukin 17 stimulates C reactive protein expression in hepatocytes and smooth muscle cells via p38 MAPK and ERK1/2 dependent NF kappaB and C/EBPbeta activation. J Biol Chem. 2007;282(37):27229-27238. doi:10.1074/jbc.M704172200
31. Eid RE, Rao DA, Zhou J, et al. Interleukin 17 and interferon gamma are produced concomitantly by human coronary artery infiltrating T cells and act synergistically on vascular smooth muscle cells. Circulation. 2009;119(10):1424-1432. doi:10.1161/CIRCULATIONAHA.108.827618
32. Ameisen JC. Apoptosis subversion: HIV Nef provides both armor and sword. Nat Med. 2001;7(11):1181-1182. doi:10.1038/nm1101-1181
33. Centers for Disease Control and Prevention. About adult BMI. Updated 2024. Accessed January 21, 2026. https://www.cdc.gov/bmi/adult-calculator/bmi-categories.html
34. Arons A, Seligman HK. The emerging adulthood gap in diabetes prevention research. Lancet Reg Health Am. 2024;32:100699. doi:10.1016/j.lana.2024.100699
35. Manjn M, Martinez O. The chi-squared goodness-of-fit test for count-data models. Stata J. 2014;14(4):798-816. doi:10.1177/1536867X1401400407
36. Favero LP, Belfiore P, Santos MA, Souza RF. overdisp: a Stata (and Mata) package for direct detection of overdispersion in Poisson and negative binomial regression models. Stat Optim Inf Comput. 2020;8(3):773-789. doi:10.19139/soic-2310-5070-557
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