New onset type 2 diabetes mellitus risks with integrase strand transfer inhibitors-based regimens: A systematic review and meta-analysis.

Violet Dismas Kajogoo, Wondwossen Amogne, Girmay Medhin
Author Information
  1. Violet Dismas Kajogoo: Center for Innovative Drug Development and Therapeutic Trials for Africa (CDT- Africa), College of Health Sciences, Addis Ababa University, Ethiopia.
  2. Wondwossen Amogne: Center for Innovative Drug Development and Therapeutic Trials for Africa (CDT- Africa), College of Health Sciences, Addis Ababa University, Ethiopia.
  3. Girmay Medhin: Center for Innovative Drug Development and Therapeutic Trials for Africa (CDT- Africa), College of Health Sciences, Addis Ababa University, Ethiopia.

Abstract

Objectives: The development of diabetes mellitus (DM) in patients taking integrase strand transfer inhibitors (INSTIs) has raised concerns. It's critical because, in most guidelines, INSTIs are the preferred third agent at first-line regimens. This study investigates the excess risk of developing DM among people living with HIV (PWH) on INSTIs-based regimens compared to those with other combination antiretroviral therapies (cART).
Methods: A search from PubMed, clinicaltrials.gov, Latin America and Caribbean health sciences literature, Cochrane, and google scholar to retrieve case-control and cohort studies were done. The literature search was performed for studies from January 2007 to January 2021. Data were extracted from studies and pooled as risk ratios (RR) with a 95% confidence interval (CI) using Stata 14 software. The protocol was registered in PROSPERO, ID: CRD42021230282.
Results: This review included ten studies, resulting in 62 400 participants. There was no significant difference in the incidence of DM between participants receiving INSTIs-based regimens versus other cARTs (RR 0.97, 95% CI: 0.92-1.03; participants = 50 958; studies = 4; I = 86.8%, chi-square = 22.67). There is no statistically significant difference in DM among people treated with INSTIs-based regimens compared to those treated with boosted protease inhibitors (PIs)-based regimens (RR 0.97, 95% CI 0.92-1.03; participants = 49 840; studies = 3; I = 89.3%, chi-square = 18.65). DM incidence was lower in INSTIs-based regimens than in those using non-nucleoside reverse transcriptase inhibitors (NNRTIs)-based regimens (RR 0.80, 95% CI 0.69-0.91; participants = 42 346; studies = 2; I = 0%, chi-square = 0.18).
Conclusion: The present review shows a nonsignificant difference in the incidence of DM in patients receiving INSTIs-based regimens compared to other regimens. However, there was a lower incidence of DM in the INSTIs group compared to the NNRTIs-based and PIs compared to the NNRTIs-based. When the INSTIs drugs dolutegravir, raltegravir, and elvitegravir were compared, there was a lower incidence of DM in raltegravir compared with elvitegravir.

Keywords

References

  1. Front Pharmacol. 2021 Nov 01;12:635089 [PMID: 34790115]
  2. Clin Infect Dis. 2020 Mar 17;70(7):1275-1277 [PMID: 31100105]
  3. BMJ. 2015 Jan 02;350:g7647 [PMID: 25555855]
  4. Malar J. 2021 Apr 1;20(1):174 [PMID: 33794897]
  5. J Int AIDS Soc. 2019 Jan;22(1):e25236 [PMID: 30697944]
  6. SAGE Open Med. 2022 Jan 30;10:20503121211072748 [PMID: 35127096]
  7. Lancet HIV. 2019 Dec;6(12):e831-e859 [PMID: 31439534]
  8. J Acquir Immune Defic Syndr. 2020 Nov 1;85(3):355-362 [PMID: 33060420]
  9. Clin Infect Dis. 2018 Apr 3;66(8):1230-1238 [PMID: 29149237]
  10. BMC Health Serv Res. 2020 Aug 1;20(1):705 [PMID: 32738918]
  11. J Antimicrob Chemother. 2020 Nov 1;75(11):3344-3348 [PMID: 32791523]
  12. Lancet Infect Dis. 2013 Nov;13(11):964-75 [PMID: 24156897]
  13. Diabetes Care. 2010 Oct;33(10):2244-9 [PMID: 20664016]
  14. Lancet HIV. 2016 Aug;3(8):e361-e387 [PMID: 27470028]
  15. PLoS One. 2016 Aug 10;11(8):e0160797 [PMID: 27508301]
  16. Semin Reprod Med. 2015 Jan;33(1):35-40 [PMID: 25565510]
  17. Clin Infect Dis. 2022 Dec 19;75(12):2060-2065 [PMID: 35521785]
  18. AIDS. 2017 Jan 2;31(1):113-125 [PMID: 27677165]
  19. J Acquir Immune Defic Syndr. 2014 Sep 1;67 Suppl 1:S40-53 [PMID: 25117960]
  20. Syst Rev. 2019 Jan 3;8(1):4 [PMID: 30606249]
  21. Lancet HIV. 2019 Dec;6(12):e809-e811 [PMID: 31439533]
  22. J Comorb. 2020 Mar 15;10:2235042X19899319 [PMID: 32206632]
  23. AIDS. 2007 Aug 20;21(13):1739-45 [PMID: 17690572]
  24. Clin Infect Dis. 2020 Mar 17;70(7):1267-1274 [PMID: 31100116]
  25. Antivir Ther. 2020;25(2):61-71 [PMID: 32118584]
  26. Clin Infect Dis. 2021 Oct 5;73(7):e2234-e2242 [PMID: 32936919]
  27. AIDS. 2005 Sep 2;19(13):1375-83 [PMID: 16103768]
  28. Clin Infect Dis. 2020 Sep 12;71(6):1390-1392 [PMID: 31608360]
  29. PLoS One. 2020 Dec 31;15(12):e0244067 [PMID: 33382732]
  30. Int J STD AIDS. 2018 Apr;29(5):443-452 [PMID: 28956700]
  31. Rev Saude Publica. 2009 Apr;43(2):283-90 [PMID: 19225696]
  32. Lancet HIV. 2020 Jul;7(7):e461-e462 [PMID: 32105626]
  33. Open Forum Infect Dis. 2021 Apr 16;8(5):ofab077 [PMID: 33981777]
  34. Clin Diabetes. 2017 Oct;35(4):232-238 [PMID: 29109613]
  35. Diabetes Care. 2003 Nov;26(11):3160-7 [PMID: 14578255]
  36. AIDS. 2021 Jan 1;35(1):81-90 [PMID: 33048874]
  37. J Acquir Immune Defic Syndr. 2014 Sep 1;67 Suppl 1:S99-103 [PMID: 25117967]
  38. AIDS. 2012 Jan 28;26(3):303-14 [PMID: 22089377]
  39. Ther Clin Risk Manag. 2008 Apr;4(2):493-500 [PMID: 18728839]
  40. BMJ Open Diabetes Res Care. 2017 Nov 26;5(1):e000457 [PMID: 29225896]
  41. AIDS. 2014 Jun 19;28(10):1451-61 [PMID: 24637543]
  42. J Antimicrob Chemother. 2018 Jan 1;73(1):258-260 [PMID: 29077869]