Skip to main content

Advertisement

SpringerLink
Log in

Diabetes in HIV: the Link to Weight Gain

  • Complications of HIV and Antiretroviral Therapy (GA McComsey, Section Editor)
  • Published:
Current HIV/AIDS Reports Aims and scope Submit manuscript

Abstract

Purpose of Review

The burden of metabolic diseases, including type 2 diabetes mellitus (T2DM), is rising among persons with HIV (PWH) on antiretroviral therapy (ART). This increase coincides with an aging population and a greater proportion who are overweight/obese. This review summarizes the changing epidemic of T2DM on contemporary ART, the role of weight gain, and therapeutic options.

Recent Findings

Recent studies confirm that PWH face an epidemic of obesity and T2DM, similar to the general population. Contemporary ART is associated with greater weight gain and may contribute to the risk of T2DM. Recent advances in medical weight loss therapy offer a way forward in the prevention and treatment of weight-associated T2DM.

Summary

Weight gain is one of the biggest contributors to T2DM in PWH. Future studies on the role of adipose tissue distribution, adipose tissue function and clinical use of effective weight loss medications may change the paradigm of care for PWH.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

We’re sorry, something doesn't seem to be working properly.

Please try refreshing the page. If that doesn't work, please contact support so we can address the problem.

Similar content being viewed by others

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Koethe JR, Jenkins CA, Lau B, Shepherd BE, Justice AC, Tate JP, Buchacz K, Napravnik S, Mayor AM, Horberg MA, et al. Rising obesity prevalence and weight gain among adults starting antiretroviral therapy in the United States and Canada. AIDS Res Hum Retroviruses. 2016;32:50–8. https://doi.org/10.1089/aid.2015.0147.

    Article  Google Scholar 

  2. •• Sax PE, Erlandson KM, Lake JE, McComsey GA, Orkin C, Esser S, Brown TT, Rockstroh JK, Wei X, Carter CC, et al. Weight gain following initiation of antiretroviral therapy: risk factors in randomized comparative clinical trials. Clin Infect Dis. 2020;71:1379–89. https://doi.org/10.1093/cid/ciz999. Pooled Analysis of ART-associated weight gain in ART naïve patients starting therapy.

    Article  CAS  Google Scholar 

  3. Bourgi K, Jenkins CA, Rebeiro PF, Palella F, Moore RD, Altoff KN, Gill J, Rabkin CS, Gange SJ, Horberg MA, et al. Weight gain among treatment-naive 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:e25484. https://doi.org/10.1002/jia2.25484.

    Article  Google Scholar 

  4. Duncan AD, Goff LM, Peters BS. Type 2 diabetes prevalence and its risk factors in HIV: a cross-sectional study. PLoS ONE. 2018;13:e0194199. https://doi.org/10.1371/journal.pone.0194199.

    Article  CAS  Google Scholar 

  5. Hernandez-Romieu AC, Garg S, Rosenberg ES, Thompson-Paul AM, Skarbinski J. Is diabetes prevalence higher among HIV-infected individuals compared with the general population? Evidence from MMP and NHANES 2009–2010. BMJ Open Diabetes Res Care. 2017;5:e000304. https://doi.org/10.1136/bmjdrc-2016-000304.

    Article  Google Scholar 

  6. Worm SW, De Wit S, Weber R, Sabin CA, Reiss P, El-Sadr W, Monforte AD, Kirk O, Fontas E, Dabis F, et al. Diabetes mellitus, preexisting coronary heart disease, and the risk of subsequent coronary heart disease events in patients infected with human immunodeficiency virus: the Data Collection on Adverse Events of Anti-HIV Drugs (D:A: D Study). Circulation. 2009;119:805–11. https://doi.org/10.1161/CIRCULATIONAHA.108.790857.

    Article  Google Scholar 

  7. Putcharoen O, Wattanachanya L, Sophonphan J, Siwamogsatham S, Sapsirisavat V, Gatechompol S, Phonphithak S, Kerr SJ, Chattranukulchai P, Avihingsanon Y, et al. New-onset diabetes in HIV-treated adults: predictors, long-term renal and cardiovascular outcomes. AIDS. 2017;31:1535–43. https://doi.org/10.1097/QAD.0000000000001496.

    Article  Google Scholar 

  8. McCutchan JA, Marquie-Beck JA, Fitzsimons CA, Letendre SL, Ellis RJ, Heaton RK, Wolfson T, Rosario D, Alexander TJ, Marra C, et al. Role of obesity, metabolic variables, and diabetes in HIV-associated neurocognitive disorder. Neurology. 2012;78:485–92. https://doi.org/10.1212/WNL.0b013e3182478d64.

    Article  CAS  Google Scholar 

  9. Nansseu JR, Bigna JJ, Kaze AD, Noubiap JJ. Incidence and risk factors for prediabetes and diabetes mellitus among HIV-infected adults on antiretroviral therapy: a systematic review and meta-analysis. Epidemiol. 2018;29:431–41. https://doi.org/10.1097/EDE.0000000000000815.

    Article  Google Scholar 

  10. McMahon CN, Petoumenos K, Hesse K, Carr A, Cooper DA, Samaras K. High rates of incident diabetes and prediabetes are evident in men with treated HIV followed for 11 years. AIDS. 2018;32:451–9. https://doi.org/10.1097/QAD.0000000000001709.

    Article  Google Scholar 

  11. Slama L, Barrett BW, Abraham AG, Palella FJ Jr, Kingsley L, Viard JP, Lake JE, Brown TT, Multicenter ACS. risk for incident diabetes is greater in prediabetic men with HIV than without HIV. AIDS. 2021;35:1605–14. https://doi.org/10.1097/QAD.0000000000002922.

    Article  Google Scholar 

  12. Yuh B, Tate J, Butt AA, Crothers K, Freiberg M, Leaf D, Logeais M, Rimland D, Rodriguez-Barradas MC, Ruser C, et al. Weight change after antiretroviral therapy and mortality. Clin Infect Dis. 2015;60:1852–9. https://doi.org/10.1093/cid/civ192.

    Article  Google Scholar 

  13. Herrin M, Tate JP, Akgun KM, Butt AA, Crothers K, Freiberg MS, Gibert CL, Leaf DA, Rimland D, Rodriguez-Barradas MC, 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. https://doi.org/10.1097/QAI.0000000000001071.

    Article  CAS  Google Scholar 

  14. •• Wilding JPH, Batterham RL, Calanna S, Davies M, Van Gaal LF, Lingvay I, McGowan BM, Rosenstock J, Tran MTD, Wadden TA, et al. Once-weekly semaglutide in adults with overweight or obesity. N Engl J Med. 2021;384:989–1002. https://doi.org/10.1056/NEJMoa2032183. Recent randomized controlled trial that demonstrated efficacy of Semaglutide as a weight loss agent. 

    Article  CAS  Google Scholar 

  15. •• Jastreboff AM, Aronne LJ, Ahmad NN, Wharton S, Connery L, Alves B, Kiyosue A, Zhang S, Liu B, Bunck MC, et al. Tirzepatide once weekly for the treatment of obesity. N Engl J Med. 2022;387:205. https://doi.org/10.1056/NEJMoa2206038. Recent randomized controlled trial that demonstrated efficacy of tirzepatide as a weight loss agent.

    Article  CAS  Google Scholar 

  16. Grunfeld C, Feingold KR. Metabolic disturbances and wasting in the acquired immunodeficiency syndrome. N Engl J Med. 1992;327:329–37. https://doi.org/10.1056/NEJM199207303270506.

    Article  CAS  Google Scholar 

  17. Macallan DC, McNurlan MA, Milne E, Calder AG, Garlick PJ, Griffin GE. Whole-body protein turnover from leucine kinetics and the response to nutrition in human immunodeficiency virus infection. Am J Clin Nutr. 1995;61:818–26. https://doi.org/10.1093/ajcn/61.4.818.

    Article  CAS  Google Scholar 

  18. Rasmussen LD, Mathiesen ER, Kronborg G, Pedersen C, Gerstoft J, Obel N. Risk of diabetes mellitus in persons with and without HIV: a Danish nationwide population-based cohort study. PLoS ONE. 2012;7:e44575. https://doi.org/10.1371/journal.pone.0044575.

    Article  CAS  Google Scholar 

  19. Brown TT, Cole SR, Li X, Kingsley LA, Palella FJ, Riddler SA, Visscher BR, Margolick JB, Dobs AS. Antiretroviral therapy and the prevalence and incidence of diabetes mellitus in the multicenter AIDS cohort study. Arch Intern Med. 2005;165:1179–84. https://doi.org/10.1001/archinte.165.10.1179.

    Article  Google Scholar 

  20. Capeau J, Bouteloup V, Katlama C, Bastard JP, Guiyedi V, Salmon-Ceron D, Protopopescu C, Leport C, Raffi F, Chene G, et al. Ten-year diabetes incidence in 1046 HIV-infected patients started on a combination antiretroviral treatment. AIDS. 2012;26:303–14. https://doi.org/10.1097/QAD.0b013e32834e8776.

    Article  CAS  Google Scholar 

  21. Hogh J, Gelpi M, Hove-Skovsgaard M, Afzal S, Nordestgaard BG, Gerstoft J, Benfield T, Storgaard H, Nielsen SD. HIV infection is associated with type 2 diabetes mellitus. J Acquir Immune Defic Syndr. 2021;88:e32–5. https://doi.org/10.1097/QAI.0000000000002798.

    Article  CAS  Google Scholar 

  22. International Expert C. International Expert Committee report on the role of the A1C assay in the diagnosis of diabetes. Diabetes Care. 2009;32:1327–34. https://doi.org/10.2337/dc09-9033.

    Article  CAS  Google Scholar 

  23. American Diabetes Association Professional Practice C: 2. Classification and diagnosis of diabetes: standards of medical care in diabetes-2022. Diabetes Care. 2022;45:S17–38. https://doi.org/10.2337/dc22-S002.

    Article  Google Scholar 

  24. Slama L, Palella FJ Jr, Abraham AG, Li X, Vigouroux C, Pialoux G, Kingsley L, Lake JE, Brown TT. Inaccuracy of haemoglobin A1c among HIV-infected men: effects of CD4 cell count, antiretroviral therapies and haematological parameters. J Antimicrob Chemother. 2014;69:3360–7. https://doi.org/10.1093/jac/dku295.

    Article  CAS  Google Scholar 

  25. Kim PS, Woods C, Georgoff P, Crum D, Rosenberg A, Smith M, Hadigan C. A1C underestimates glycemia in HIV infection. Diabetes Care. 2009;32:1591–3. https://doi.org/10.2337/dc09-0177.

    Article  CAS  Google Scholar 

  26. Eckhardt BJ, Holzman RS, Kwan CK, Baghdadi J, Aberg JA. Glycated hemoglobin A(1c) as screening for diabetes mellitus in HIV-infected individuals. AIDS Patient Care STDS. 2012;26:197–201. https://doi.org/10.1089/apc.2011.0379.

    Article  Google Scholar 

  27. Monroe AK, Glesby MJ, Brown TT. Diagnosing and managing diabetes in HIV-infected patients: current concepts. Clin Infect Dis. 2015;60:453–62. https://doi.org/10.1093/cid/ciu779.

    Article  CAS  Google Scholar 

  28. Butt AA, McGinnis K, Rodriguez-Barradas MC, Crystal S, Simberkoff M, Goetz MB, Leaf D, Justice AC. Veterans Aging Cohort S: HIV infection and the risk of diabetes mellitus. AIDS. 2009;23:1227–34. https://doi.org/10.1097/QAD.0b013e32832bd7af.

    Article  Google Scholar 

  29. Tien PC, Schneider MF, Cole SR, Levine AM, Cohen M, DeHovitz J, Young M, Justman JE. Antiretroviral therapy exposure and incidence of diabetes mellitus in the Women’s Interagency HIV Study. AIDS. 2007;21:1739–45. https://doi.org/10.1097/QAD.0b013e32827038d0.

    Article  CAS  Google Scholar 

  30. Grunfeld C, Saag M, Cofrancesco J Jr, Lewis CE, Kronmal R, Heymsfield S, Tien PC, Bacchetti P, Shlipak M, Scherzer R, et al. Regional adipose tissue measured by MRI over 5 years in HIV-infected and control participants indicates persistence of HIV-associated lipoatrophy. AIDS. 2010;24:1717–26. https://doi.org/10.1097/QAD.0b013e32833ac7a2.

    Article  Google Scholar 

  31. Neuhaus J, Jacobs DR Jr, Baker JV, Calmy A, Duprez D, La Rosa A, Kuller LH, Pett SL, Ristola M, Ross MJ, et al. Markers of inflammation, coagulation, and renal function are elevated in adults with HIV infection. J Infect Dis. 2010;201:1788–95. https://doi.org/10.1086/652749.

    Article  CAS  Google Scholar 

  32. Brown TT, Tassiopoulos K, Bosch RJ, Shikuma C, McComsey GA. Association between systemic inflammation and incident diabetes in HIV-infected patients after initiation of antiretroviral therapy. Diabetes Care. 2010;33:2244–9. https://doi.org/10.2337/dc10-0633.

    Article  Google Scholar 

  33. Betene ADC, De Wit S, Neuhaus J, Palfreeman A, Pepe R, Pankow JS, Neaton JD, Insight S, Groups ES. Interleukin-6, high sensitivity C-reactive protein, and the development of type 2 diabetes among HIV-positive patients taking antiretroviral therapy. J Acquir Immune Defic Syndr. 2014;67:538–46. https://doi.org/10.1097/QAI.0000000000000354.

    Article  CAS  Google Scholar 

  34. Bailin SS, Kundu S, Wellons M, Freiberg MS, Doyle MF, Tracy RP, Justice AC, Wanjalla CN, Landay AL, So-Armah K, et al. Circulating CD4+ TEMRA and CD4+ CD28- T cells and incident diabetes among persons with and without HIV. AIDS. 2022;36:501–11. https://doi.org/10.1097/QAD.0000000000003137.

    Article  CAS  Google Scholar 

  35. De Wit S, Sabin CA, Weber R, Worm SW, Reiss P, Cazanave C, El-Sadr W, Monforte A, Fontas E, Law MG, et al. Incidence and risk factors for new-onset diabetes in HIV-infected patients: the data collection on adverse events of anti-HIV drugs (D:A:D) study. Diabetes Care. 2008;31:1224–9. https://doi.org/10.2337/dc07-2013.

    Article  Google Scholar 

  36. Achhra AC, Sabin C, Ryom L, Hatleberg C, Antonella d’Aminio M, de Wit S, Phillips A, Pradier C, Weber R, Reiss P, et al. Body mass index and the risk of serious non-AIDS events and all-cause mortality in treated HIV-positive individuals: D: A: D cohort analysis. J Acquir Immune Defic Syndr. 2018;78:579–88. https://doi.org/10.1097/QAI.0000000000001722.

    Article  Google Scholar 

  37. Macallan DC, Noble C, Baldwin C, Jebb SA, Prentice AM, Coward WA, Sawyer MB, McManus TJ, Griffin GE. Energy expenditure and wasting in human immunodeficiency virus infection. N Engl J Med. 1995;333:83–8. https://doi.org/10.1056/NEJM199507133330202.

    Article  CAS  Google Scholar 

  38. Hasse B, Iff M, Ledergerber B, Calmy A, Schmid P, Hauser C, Cavassini M, Bernasconi E, Marzolini C, Tarr PE, et al. Obesity trends and body mass index changes after starting antiretroviral treatment: the Swiss HIV cohort study. Open Forum Infect Dis. 2014;1:ofu040. https://doi.org/10.1093/ofid/ofu040.

    Article  Google Scholar 

  39. Crum-Cianflone N, Roediger MP, Eberly L, Headd M, Marconi V, Ganesan A, Weintrob A, Barthel RV, Fraser S, Agan BK, et al. Increasing rates of obesity among HIV-infected persons during the HIV epidemic. PLoS ONE. 2010;5:e10106. https://doi.org/10.1371/journal.pone.0010106.

    Article  CAS  Google Scholar 

  40. Amorosa V, Synnestvedt M, Gross R, Friedman H, MacGregor RR, Gudonis D, Frank I, Tebas P. A tale of 2 epidemics: the intersection between obesity and HIV infection in Philadelphia. J Acquir Immune Defic Syndr. 2005;39:557–61.

    Google Scholar 

  41. Bares SH, Smeaton LM, Xu A, Godfrey C, McComsey GA. HIV-infected women gain more weight than HIV-infected men following the initiation of antiretroviral therapy. J Womens Health (Larchmt). 2018;27:1162–9. https://doi.org/10.1089/jwh.2017.6717.

    Article  Google Scholar 

  42. Taylor BS, Liang Y, Garduno LS, Walter EA, Gerardi MB, Anstead GM, Bullock D, Turner BJ. High risk of obesity and weight gain for HIV-infected uninsured minorities. J Acquir Immune Defic Syndr. 2014;65:e33-40. https://doi.org/10.1097/QAI.0000000000000010.

    Article  Google Scholar 

  43. Flegal KM, Kruszon-Moran D, Carroll MD, Fryar CD, Ogden CL. Trends in obesity among adults in the United States, 2005 to 2014. JAMA. 2016;315:2284–91. https://doi.org/10.1001/jama.2016.6458.

    Article  CAS  Google Scholar 

  44. Ghaben AL, Scherer PE. Adipogenesis and metabolic health. Nat Rev Mol Cell Biol. 2019;20:242–58. https://doi.org/10.1038/s41580-018-0093-z.

    Article  CAS  Google Scholar 

  45. Van Harmelen V, Rohrig K, Hauner H. Comparison of proliferation and differentiation capacity of human adipocyte precursor cells from the omental and subcutaneous adipose tissue depot of obese subjects. Metabolism. 2004;53:632–7. https://doi.org/10.1016/j.metabol.2003.11.012.

    Article  CAS  Google Scholar 

  46. Leroyer S, Vatier C, Kadiri S, Quette J, Chapron C, Capeau J, Antoine B. Glyceroneogenesis is inhibited through HIV protease inhibitor-induced inflammation in human subcutaneous but not visceral adipose tissue. J Lipid Res. 2011;52:207–20. https://doi.org/10.1194/jlr.M000869.

    Article  CAS  Google Scholar 

  47. Gallego-Escuredo JM, Villarroya J, Domingo P, Targarona EM, Alegre M, Domingo JC, Villarroya F, Giralt M. Differentially altered molecular signature of visceral adipose tissue in HIV-1-associated lipodystrophy. J Acquir Immune Defic Syndr. 2013;64:142–8. https://doi.org/10.1097/QAI.0b013e31829bdb67.

    Article  CAS  Google Scholar 

  48. Boyko EJ, Fujimoto WY, Leonetti DL, Newell-Morris L. Visceral adiposity and risk of type 2 diabetes: a prospective study among Japanese Americans. Diabetes Care. 2000;23:465–71. https://doi.org/10.2337/diacare.23.4.465.

    Article  CAS  Google Scholar 

  49. Neeland IJ, Turer AT, Ayers CR, Powell-Wiley TM, Vega GL, Farzaneh-Far R, Grundy SM, Khera A, McGuire DK, de Lemos JA. Dysfunctional adiposity and the risk of prediabetes and type 2 diabetes in obese adults. JAMA. 2012;308:1150–9. https://doi.org/10.1001/2012.jama.11132.

    Article  CAS  Google Scholar 

  50. Orlando G, Guaraldi G, Zona S, Carli F, Bagni P, Menozzi M, Cocchi S, Scaglioni R, Ligabue G, Raggi P. Ectopic fat is linked to prior cardiovascular events in men with HIV. J Acquir Immune Defic Syndr. 2012;59:494–7. https://doi.org/10.1097/QAI.0b013e31824c8397.

    Article  Google Scholar 

  51. Guaraldi G, Scaglioni R, Zona S, Orlando G, Carli F, Ligabue G, Besutti G, Bagni P, Rossi R, Modena MG, et al. Epicardial adipose tissue is an independent marker of cardiovascular risk in HIV-infected patients. AIDS. 2011;25:1199–205. https://doi.org/10.1097/QAD.0b013e3283474b9f.

    Article  Google Scholar 

  52. Gan SK, Samaras K, Thompson CH, Kraegen EW, Carr A, Cooper DA, Chisholm DJ. Altered myocellular and abdominal fat partitioning predict disturbance in insulin action in HIV protease inhibitor-related lipodystrophy. Diabetes. 2002;51:3163–9. https://doi.org/10.2337/diabetes.51.11.3163.

    Article  CAS  Google Scholar 

  53. Reeds DN, Yarasheski KE, Fontana L, Cade WT, Laciny E, DeMoss A, Patterson BW, Powderly WG, Klein S. Alterations in liver, muscle, and adipose tissue insulin sensitivity in men with HIV infection and dyslipidemia. Am J Physiol Endocrinol Metab. 2006;290:E47–53. https://doi.org/10.1152/ajpendo.00236.2005.

    Article  CAS  Google Scholar 

  54. Giralt M, Domingo P, Guallar JP. Rodriguez de la Concepcion ML, Alegre M, Domingo JC, Villarroya F: HIV-1 infection alters gene expression in adipose tissue, which contributes to HIV- 1/HAART-associated lipodystrophy. Antivir Ther. 2006;11:729–40.

    Article  CAS  Google Scholar 

  55. Diaz-Delfin J, Domingo P, Wabitsch M, Giralt M, Villarroya F. HIV-1 Tat protein impairs adipogenesis and induces the expression and secretion of proinflammatory cytokines in human SGBS adipocytes. Antivir Ther. 2012;17:529–40. https://doi.org/10.3851/IMP2021.

    Article  CAS  Google Scholar 

  56. Koethe JR, Lagathu C, Lake JE, Domingo P, Calmy A, Falutz J, Brown TT, Capeau J. HIV and antiretroviral therapy-related fat alterations. Nat Rev Dis Primers. 2020;6:48. https://doi.org/10.1038/s41572-020-0181-1.

    Article  Google Scholar 

  57. Debroy P, Feng H, Miao H, Milic J, Ligabue G, Draisci S, Besutti G, Carli F, Menozzi M, Mussini C, et al. Changes in central adipose tissue after switching to integrase inhibitors. HIV Res Clin Pract. 2020;21:168–73. https://doi.org/10.1080/25787489.2020.1848131.

    Article  CAS  Google Scholar 

  58. Ouchi N, Parker JL, Lugus JJ, Walsh K. Adipokines in inflammation and metabolic disease. Nat Rev Immunol. 2011;11:85–97. https://doi.org/10.1038/nri2921.

    Article  CAS  Google Scholar 

  59. Wanjalla CN, McDonnell WJ, Koethe JR. Adipose tissue T cells in HIV/SIV infection. Front Immunol. 2018;9:2730. https://doi.org/10.3389/fimmu.2018.02730.

    Article  CAS  Google Scholar 

  60. Bourgeois C, Gorwood J, Olivo A, Le Pelletier L, Capeau J, Lambotte O, Bereziat V, Lagathu C. contribution of adipose tissue to the chronic immune activation and inflammation associated with HIV infection and its treatment. Front Immunol. 2021;12:670566. https://doi.org/10.3389/fimmu.2021.670566.

    Article  CAS  Google Scholar 

  61. Podany AT, Scarsi KK, Fletcher CV. comparative clinical pharmacokinetics and pharmacodynamics of HIV-1 integrase strand transfer inhibitors. Clin Pharmacokinet. 2017;56:25–40. https://doi.org/10.1007/s40262-016-0424-1.

    Article  CAS  Google Scholar 

  62. Panel on antiviral guidelines for adults and adolescents: guidelines for the use of antiretroviral agents in adults and adolescents with HIV. Services DoHaH. Available At https://clinicalinfo.hiv.gov/sites/default/files/guidelines/archive/AdultandAdolescentGL_2021_08_16.pdf. Accessed 7/02/22

  63. •• Venter WDF, Moorhouse M, Sokhela S, Fairlie L, Mashabane N, Masenya M, Serenata C, Akpomiemie G, Qavi A, Chandiwana N, et al. Dolutegravir plus two different prodrugs of tenofovir to treat HIV. N Engl J Med. 2019;381:803–15. https://doi.org/10.1056/NEJMoa1902824. Randomized clinical trial evaluating dolutegravir with one of two formulations of tenofovir with efavirenz.

    Article  CAS  Google Scholar 

  64. Bourgi K, Rebeiro PF, Turner M, Castilho JL, Hulgan T, Raffanti SP, Koethe JR, Sterling TR. Greater weight gain in treatment-naive persons starting dolutegravir-based antiretroviral therapy. Clin Infect Dis. 2020;70:1267–74. https://doi.org/10.1093/cid/ciz407.

    Article  CAS  Google Scholar 

  65. Bakal DR, Coelho LE, Luz PM, Clark JL, De Boni RB, Cardoso SW, Veloso VG, Lake JE, Grinsztejn B. Obesity following ART initiation is common and influenced by both traditional and HIV-/ART-specific risk factors. J Antimicrob Chemother. 2018;73:2177–85. https://doi.org/10.1093/jac/dky145.

    Article  Google Scholar 

  66. Group NAS, Kouanfack C, Mpoudi-Etame M, OmgbaBassega P, Eymard-Duvernay S, Leroy S, Boyer S, Peeters M, Calmy A, Delaporte E. dolutegravir-based or low-dose efavirenz-based regimen for the treatment of HIV-1. N Engl J Med. 2019;381:816–26. https://doi.org/10.1056/NEJMoa1904340.

    Article  Google Scholar 

  67. Rizzardo S, Lanzafame M, Lattuada E, Luise D, Vincenzi M, Tacconelli E, Vento S. Dolutegravir monotherapy and body weight gain in antiretroviral naive patients. AIDS. 2019;33:1673–4. https://doi.org/10.1097/QAD.0000000000002245.

    Article  Google Scholar 

  68. Menard A, Meddeb L, Tissot-Dupont H, Ravaux I, Dhiver C, Mokhtari S, Tomei C, Brouqui P, Colson P, Stein A. Dolutegravir and weight gain: an unexpected bothering side effect? AIDS. 2017;31:1499–500. https://doi.org/10.1097/QAD.0000000000001495.

    Article  Google Scholar 

  69. Kerchberger AM, Sheth AN, Angert CD, Mehta CC, Summers NA, Ofotokun I, Gustafson D, Weiser SD, Sharma A, Adimora AA, et al. Weight gain associated with integrase stand transfer inhibitor use in women. Clin Infect Dis. 2020;71:593–600. https://doi.org/10.1093/cid/ciz853.

    Article  CAS  Google Scholar 

  70. McComsey GA, Moser C, Currier J, Ribaudo HJ, Paczuski P, Dube MP, Kelesidis T, Rothenberg J, Stein JH, Brown TT. Body composition changes after initiation of raltegravir or protease inhibitors: ACTG A5260s. Clin Infect Dis. 2016;62:853–62. https://doi.org/10.1093/cid/ciw017.

    Article  CAS  Google Scholar 

  71. Debroy P, Sim M, Erlandson KM, Falutz J, Prado CM, Brown TT, Guaraldi G, Lake JE. Progressive increases in fat mass occur in adults living with HIV on antiretroviral therapy, but patterns differ by sex and anatomic depot. J Antimicrob Chemother. 2019;74:1028–34. https://doi.org/10.1093/jac/dky551.

    Article  CAS  Google Scholar 

  72. • Lake JE, Wu K, Bares SH, Debroy P, Godfrey C, Koethe JR, McComsey GA, Palella FJ, Tassiopoulos K, Erlandson KM. Risk factors for weight gain following switch to integrase inhibitor-based antiretroviral therapy. Clin Infect Dis. 2020;71:e471–7. https://doi.org/10.1093/cid/ciaa177. Assessed the risk factors for weight gain in PWH switched to an INSTI-based regimen.

    Article  CAS  Google Scholar 

  73. Mallon PW, Brunet L, Hsu RK, Fusco JS, Mounzer KC, Prajapati G, Beyer AP, Wohlfeiler MB, Fusco GP. Weight gain before and after switch from TDF to TAF in a U.S. cohort study. J Int AIDS Soc. 2021;24:e25702. https://doi.org/10.1002/jia2.25702.

    Article  CAS  Google Scholar 

  74. Shah S, Pilkington V, Hill A. Is tenofovir disoproxil fumarate associated with weight loss? AIDS. 2021;35:S189–95. https://doi.org/10.1097/QAD.0000000000003083.

    Article  CAS  Google Scholar 

  75. Gianotti N, Muccini C, Galli L, Poli A, Spagnuolo V, Andolina A, Galizzi N, Ripa M, Messina E, Piatti PM, et al. Homeostatic model assessment for insulin resistance index trajectories in HIV-infected patients treated with different first-line antiretroviral regimens. J Med Virol. 2019;91:1937–43. https://doi.org/10.1002/jmv.25541.

    Article  CAS  Google Scholar 

  76. Calza L, Colangeli V, Borderi M, Coladonato S, Tazza B, Bon I, Re MC, Viale P. Improvement in insulin sensitivity and serum leptin concentration after the switch from a ritonavir-boosted PI to raltegravir or dolutegravir in non-diabetic HIV-infected patients. J Antimicrob Chemother. 2019;74:731–8. https://doi.org/10.1093/jac/dky507.

    Article  CAS  Google Scholar 

  77. O’Halloran JA, Sahrmann J, Parra-Rodriguez L, Vo DT, Butler AM, Olsen MA, Powderly WG: Integrase strand transfer inhibitors are associated with incident diabetes mellitus in people with HIV. Clin Infect Dis. 2022. https://doi.org/10.1093/cid/ciac355

  78. Summers NA, Lahiri CD, Angert CD, Aldredge A, Mehta CC, Ofotokun I, Kerchberger AM, Gustafson D, Weiser SD, Kassaye S, et al. Metabolic changes associated with the use of integrase strand transfer inhibitors among virally controlled women. J Acquir Immune Defic Syndr. 2020;85:355–62. https://doi.org/10.1097/QAI.0000000000002447.

    Article  CAS  Google Scholar 

  79. Ursenbach A, Max V, Maurel M, Bani-Sadr F, Gagneux-Brunon A, Garraffo R, Ravaux I, Robineau O, Makinson A, Rey D, et al. Incidence of diabetes in HIV-infected patients treated with first-line integrase strand transfer inhibitors: a French multicentre retrospective study. J Antimicrob Chemother. 2020;75:3344–8. https://doi.org/10.1093/jac/dkaa330.

    Article  CAS  Google Scholar 

  80. Hsu R, Brunet L, Fusco JS, Mounzer K, Vannappagari V, Henegar CE, Van Wyk J, Curtis L, Lo J, Fusco GP. Incident type 2 diabetes mellitus after initiation of common HIV antiretroviral drugs. AIDS. 2021;35:81–90. https://doi.org/10.1097/QAD.0000000000002718.

    Article  CAS  Google Scholar 

  81. •• Rebeiro PF, Jenkins CA, Bian A, Lake JE, Bourgi K, Moore RD, Horberg MA, Matthews WC, Silverberg MJ, Thorne J, et al. Risk of incident diabetes mellitus, weight gain, and their relationships with integrase inhibitor-based initial antiretroviral therapy among persons with human immunodeficiency virus in the United States and Canada. Clin Infect Dis. 2021;73:e2234–42. https://doi.org/10.1093/cid/ciaa1403. NA-ACCORD Study that found INSTI-based regimens may be associated with incident diabetes, mainly mediated through weight gain.

    Article  CAS  Google Scholar 

  82. McCann K, Shah S, Hindley L, Hill A, Qavi A, Simmons B, Serenata C, Sokhela S, Venter WDF. Implications of weight gain with newer anti-retrovirals: 10-year predictions of cardiovascular disease and diabetes. AIDS. 2021;35:1657–65. https://doi.org/10.1097/QAD.0000000000002930.

    Article  Google Scholar 

  83. Abraham AG, Althoff KN, Jing Y, Estrella MM, Kitahata MM, Wester CW, Bosch RJ, Crane H, Eron J, Gill MJ, et al. End-stage renal disease among HIV-infected adults in North America. Clin Infect Dis. 2015;60:941–9. https://doi.org/10.1093/cid/ciu919.

    Article  Google Scholar 

  84. Guaraldi G, Squillace N, Stentarelli C, Orlando G, D’Amico R, Ligabue G, Fiocchi F, Zona S, Loria P, Esposito R, et al. Nonalcoholic fatty liver disease in HIV-infected patients referred to a metabolic clinic: prevalence, characteristics, and predictors. Clin Infect Dis. 2008;47:250–7. https://doi.org/10.1086/589294.

    Article  Google Scholar 

  85. Maurice JB, Goldin R, Hall A, Price JC, Sebastiani G, Morse CG, Prat LI, Perazzo H, Garvey L, Ingiliz P, et al. Increased body mass index and type 2 diabetes are the main predictors of nonalcoholic fatty liver disease and advanced fibrosis in liver biopsies of patients with human immunodeficiency virus monoinfection. Clin Infect Dis. 2021;73:e2184–93. https://doi.org/10.1093/cid/ciaa1302.

    Article  CAS  Google Scholar 

  86. Roubenoff R, Weiss L, McDermott A, Heflin T, Cloutier GJ, Wood M, Gorbach S. A pilot study of exercise training to reduce trunk fat in adults with HIV-associated fat redistribution. AIDS. 1999;13:1373–5. https://doi.org/10.1097/00002030-199907300-00015.

    Article  CAS  Google Scholar 

  87. Becofsky K, Wing EJ, McCaffery J, Boudreau M, Wing RR. A randomized controlled trial of a behavioral weight loss program for human immunodeficiency virus-infected patients. Clin Infect Dis. 2017;65:154–7. https://doi.org/10.1093/cid/cix238.

    Article  Google Scholar 

  88. Canuto R, Garcez A, de Souza RV, Kac G, Olinto MTA. Nutritional intervention strategies for the management of overweight and obesity in primary health care: a systematic review with meta-analysis. Obes Rev. 2021;22:e13143. https://doi.org/10.1111/obr.13143.

    Article  Google Scholar 

  89. Tak YJ, Lee SY. Long-term efficacy and safety of anti-obesity treatment: where do we stand? Curr Obes Rep. 2021;10:14–30. https://doi.org/10.1007/s13679-020-00422-w.

    Article  Google Scholar 

  90. Buchwald H, Avidor Y, Braunwald E, Jensen MD, Pories W, Fahrbach K, Schoelles K. Bariatric surgery: a systematic review and meta-analysis. JAMA. 2004;292:1724–37. https://doi.org/10.1001/jama.292.14.1724.

    Article  CAS  Google Scholar 

  91. Mingrone G, Panunzi S, De Gaetano A, Guidone C, Iaconelli A, Nanni G, Castagneto M, Bornstein S, Rubino F. Bariatric-metabolic surgery versus conventional medical treatment in obese patients with type 2 diabetes: 5 year follow-up of an open-label, single-centre, randomised controlled trial. Lancet. 2015;386:964–73. https://doi.org/10.1016/S0140-6736(15)00075-6.

    Article  Google Scholar 

  92. Akbari K, Som R, Sampson M, Abbas SH, Ramus J, Jones G. The effect of bariatric surgery on patients with HIV infection: a literature review. Obes Surg. 2018;28:2550–9. https://doi.org/10.1007/s11695-018-3319-4.

    Article  Google Scholar 

  93. Pourcher G, Peytavin G, Schneider L, Gallien S, Force G, Pourcher V. Bariatric surgery in HIV patients: experience of an Obesity Reference Center in France. Surg Obes Relat Dis. 2017;13:1990–6. https://doi.org/10.1016/j.soard.2017.09.514.

    Article  Google Scholar 

  94. Kaip EA, Nguyen NY, Cocohoba JM. Antiretroviral therapy efficacy post-bariatric weight loss surgery: a case series of persons living with human immunodeficiency virus. Obes Surg. 2022;32:1523–30. https://doi.org/10.1007/s11695-022-05956-7.

    Article  Google Scholar 

  95. Zino L, Kingma JS, Marzolini C, Richel O, Burger DM, Colbers A. Implications of bariatric surgery on the pharmacokinetics of antiretrovirals in people living with HIV. Clin Pharmacokinet. 2022;61:619–35. https://doi.org/10.1007/s40262-022-01120-7.

    Article  Google Scholar 

Download references

Funding

Dr. Bailin and Dr. Koethe received funding from the Vanderbilt Scholars in HIV and Heart, Lung, Blood and Sleep Research (V-SCHoLARS) grant K12HL143956.

Author information

Authors and Affiliations

  1. Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, 37232, USA

    Samuel S. Bailin & John R. Koethe

  2. Department of Veterans Affairs, Tennessee Valley Health System, Nashville, TN, 37212, USA

    John R. Koethe

Authors
  1. Samuel S. Bailin
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. John R. Koethe
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Samuel S. Bailin.

Ethics declarations

Conflict of Interest

S.B. has no competing interests to declare.

J.K. has served as a consultant to Gilead Sciences, Merck & Co., ViiV Healthcare, Theratechnologies and Janssen Pharmaceuticals. He has also received research support from Gilead Sciences and Merck & Co.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

This article is part of the Topical Collection on Complications of HIV and Antiretroviral Therapy.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Bailin, S.S., Koethe, J.R. Diabetes in HIV: the Link to Weight Gain. Curr HIV/AIDS Rep 20, 9–18 (2023). https://doi.org/10.1007/s11904-022-00642-w

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11904-022-00642-w

Keywords

Search

Navigation