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BMC Infectious Diseases

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Open Access 01-12-2022 | Human Immunodeficiency Virus | Research article

Effects of different integrase strand transfer inhibitors on body weight in patients with HIV/AIDS: a network meta-analysis

Authors: Ruojing Bai, Shiyun Lv, Hao Wu, Lili Dai

Published in: BMC Infectious Diseases | Issue 1/2022

Abstract

Background

Global antiretroviral therapy has entered a new era. Integrase strand transfer inhibitor (INSTI) has become the first choice in acquired immunodeficiency syndrome (AIDS) treatment. Because INSTI has high antiviral efficacy, rapid virus inhibition, and good tolerance. However, INSTIs may increase the risk of obesity. Each INSTI has its unique impact on weight gain in patients with human immunodeficiency virus (HIV)/AIDS. This study systematically assessed different INSTIs in causing significant weight gain in HIV/AIDS patients by integrating data from relevant literature.

Methods

PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure (CNKI), Chinese Biomedical Literature Database (CBM), China Science and Technology Journal Database (VIP), and Wanfang databases were searched to find studies on the influence of different INSTIs in weight gain. Data on weight change were extracted, and a network meta-analysis was performed.

Results

Eight studies reported weight changes in HIV/AIDS patients were included. Results of the network meta-analysis showed that the weight gain of HIV/AIDS patients treated with Dolutegravir (DTG) was significantly higher than that of Elvitegravir (EVG) [MD = 1.13, (0.18–2.07)]. The consistency test results showed no overall and local inconsistency, and no significant difference in the results of the direct and indirect comparison was detected (p > 0.05). The rank order of probability was DTG (79.2%) > Bictegravir (BIC) (77.9%) > Raltegravir (RAL) (33.2%) > EVG (9.7%), suggesting that DTG may be the INSTI drug that causes the most significant weight gain in HIV/AIDS patients.

Conclusion

According to the data analysis, among the existing INSTIs, DTG may be the drug that causes the most significant weight gain in HIV/AIDS patients, followed by BIC.

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Mogadam E, King K, Shriner K, Chu K, Sondergaard A, Young K, Naghavi M, Kloner RA. The association of nadir CD4-T cell count and endothelial dysfunction in a healthy HIV cohort without major cardiovascular risk factors. SAGE Open Med. 2020;8:2050312120924892.CrossRef

Ceulemans A, Bouzahzah C, Prat I, Urassa W, Kestens L. CD4-T cell enumeration in human immunodeficiency virus (HIV)-infected patients: a laboratory performance evaluation of Muse Auto CD4/CD4% system by World Health Organization prequalification of in vitro diagnostics. PLoS ONE. 2019;14(1):e0209677.CrossRef

Vangipuram R, Tyring SK. AIDS-associated malignancies. In: Meyers C, editor. HIV/AIDS-associated viral oncogenesis. Cham: Springer; 2019. p. 1–21.

Facciolà A, VenanziRullo E, Ceccarelli M, D’Andrea F, Coco M, Micali C, Cacopardo B, Marino A, Cannavò SP, DiRosa M, et al. Malignant melanoma in HIV: epidemiology, pathogenesis, and management. Dermatol Ther. 2020;33(1):e13180.CrossRef

Eckard AR, McComsey GA. Weight gain and integrase inhibitors. Curr Opin Infect Dis. 2020;33(1):10–9.CrossRef

Iwamoto M, Wenning LA, Petry AS, Laethem M, De Smet M, Kost JT, Merschman SA, Strohmaier KM, Ramael S, Lasseter KC, et al. Safety, tolerability, and pharmacokinetics of raltegravir after single and multiple doses in healthy subjects. Clin Pharmacol Ther. 2008;83(2):293–9.CrossRef

Mondi A, Cozzi-Lepri A, Tavelli A, Rusconi S, Vichi F, Ceccherini-Silberstein F, Calcagno A, De Luca A, Maggiolo F, Marchetti G, et al. Effectiveness of dolutegravir-based regimens as either first-line or switch antiretroviral therapy: data from the Icona cohort. J Int AIDS Soc. 2019;22(1):e25227–e25227.CrossRef

McComsey GA, Moser C, Currier J, Ribaudo HJ, Paczuski P, Dubé 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(7):853–62.CrossRef

European AIDS Clinical Society (EACS). Guidelines Version 10.1 (English). EACS. 2020. https://www.eacsociety.org/files/guidelines-10.1_30032021_1.pdf. Accessed 19 Mar 2021.

10.

WHO. Updated recommendations on first-line and second-line antiretroviral regimens and post-exposure prophylaxis and recommendations on early infant diagnosis of HIV. WHO. 2018. https://apps.who.int/iris/rest/bitstreams/1168419/retrieve. Accessed 19 Mar 2021.

11.

Saag MS, Benson CA, Gandhi RT, Hoy JF, Landovitz RJ, Mugavero MJ, Sax PE, Smith DM, Thompson MA, Buchbinder SP, et al. Antiretroviral drugs for treatment and prevention of HIV infection in adults: 2018 recommendations of the international antiviral society-USA panel. JAMA. 2018;320(4):379–96.CrossRef

12.

British HIV Association (BHIVA). BHIVA guidelines for the treatment of HIV-1-positive adults with antiretroviral therapy 2015 (2016 interim update). BHIVA. 2020. https://www.bhiva.org/file/RVYKzFwyxpgiI/treatment-guidelines-2016-interim-update.pdf. Accessed 19 Mar 2021.

13.

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-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–e25484.CrossRef

14.

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(6):1379–89.CrossRef

15.

Sattler FR, He J, Letendre S, Wilson C, Sanders C, Heaton R, Ellis R, Franklin D, Aldrovandi G, Marra CM, et al. Abdominal obesity contributes to neurocognitive impairment in HIV-infected patients with increased inflammation and immune activation. J Acquir Immune Defic Syndr. 2015;68(3):281–8.CrossRef

16.

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(8):2177–85.CrossRef

17.

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(12):1852–9.CrossRef

18.

Paton NI, Sangeetha S, Earnest A, Bellamy R. The impact of malnutrition on survival and the CD4 count response in HIV-infected patients starting antiretroviral therapy. HIV Med. 2006;7(5):323–30.CrossRef

19.

Madec Y, Szumilin E, Genevier C, Ferradini L, Balkan S, Pujades M, Fontanet A. Weight gain at 3 months of antiretroviral therapy is strongly associated with survival: evidence from two developing countries. AIDS. 2009;23(7):853–61.CrossRef

20.

Koethe JR, Limbada MI, Giganti MJ, Nyirenda CK, Mulenga L, Wester CW, Chi BH, Stringer JS. Early immunologic response and subsequent survival among malnourished adults receiving antiretroviral therapy in Urban Zambia. AIDS. 2010;24(13):2117–21.CrossRef

21.

Koethe JR, Lukusa A, Giganti MJ, Chi BH, Nyirenda CK, Limbada MI, Banda Y, Stringer JSA. Association between weight gain and clinical outcomes among malnourished adults initiating antiretroviral therapy in Lusaka, Zambia. J Acquir Immune Defic Syndr. 2010;53(4):507–13.CrossRef

22.

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(1):50–8.CrossRef

23.

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(4):e10106.CrossRef

24.

Lakey W, Yang L-Y, Yancy W, Chow S-C, Hicks C. Short communication: from wasting to obesity: initial antiretroviral therapy and weight gain in HIV-infected persons. AIDS Res Hum Retroviruses. 2013;29(3):435–40.CrossRef

25.

Herrin M, Tate JP, Akgün 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(2):228–36.CrossRef

26.

Calza L, Colangeli V, Borderi M, Bon I, Borioni A, Volpato F, Re MC, Viale P. Weight gain in antiretroviral therapy-naive HIV-1-infected patients starting a regimen including an integrase strand transfer inhibitor or darunavir/ritonavir. Infection. 2020;48(2):213–21.CrossRef

27.

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 HIV in the US and Canada. Clin Infect Dis. 2020. https://doi.org/10.1093/cid/ciaa1403.CrossRefPubMedPubMedCentral

28.

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(7):1267–74.CrossRef

29.

Wohl DA, Yazdanpanah Y, Baumgarten A, Clarke A, Thompson MA, Brinson C, Hagins D, Ramgopal MN, Antinori A, Wei X, et al. Bictegravir combined with emtricitabine and tenofovir alafenamide versus dolutegravir, abacavir, and lamivudine for initial treatment of HIV-1 infection: week 96 results from a randomised, double-blind, multicentre, phase 3, non-inferiority trial. Lancet HIV. 2019;6(6):e355–63.CrossRef

30.

Stellbrink HJ, Arribas JR, Stephens JL, Albrecht H, Sax PE, Maggiolo F, Creticos C, Martorell CT, Wei X, Acosta R, et al. Co-formulated bictegravir, emtricitabine, and tenofovir alafenamide versus dolutegravir with emtricitabine and tenofovir alafenamide for initial treatment of HIV-1 infection: week 96 results from a randomised, double-blind, multicentre, phase 3, non-inferiority trial. Lancet HIV. 2019;6(6):e364–72.CrossRef

31.

Lake JE, Wu K, Bares SH, Debroy P, Godfrey C, Koethe JR, McComsey GA, Palella FJ, Tassiopoulos K, Erlandson KM, et al. Risk factors for weight gain following switch to integrase inhibitor-based antiretroviral therapy. Clin Infect Dis. 2020;71(9):e471–7.CrossRef

32.

Committee for Medicinal Products for Human Use (CHMP). International non-proprietary name: dolutegravir (Tivicay). European Medicines Agency (EMA). 2020. https://www.ema.europa.eu/en/documents/assessment-report/tivicay-epar-public-assessment-report_en.pdf. Accessed 19 Mar 2021.

33.

Huszar D, Lynch CA, Fairchild-Huntress V, Dunmore JH, Fang Q, Berkemeier LR, Gu W, Kesterson RA, Boston BA, Cone RD, et al. Targeted disruption of the melanocortin-4 receptor results in obesity in mice. Cell. 1997;88(1):131–41.CrossRef

34.

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. NEJM. 1995;333(2):83–8.CrossRef

35.

Couturier J, Winchester LC, Suliburk JW, Wilkerson GK, Podany AT, Agarwal N, Xuan Chua CY, Nehete PN, Nehete BP, Grattoni A, et al. Adipocytes impair efficacy of antiretroviral therapy. Antiviral Res. 2018;154:140–8.CrossRef

36.

Moure R, Domingo P, Gallego-Escuredo JM, Villarroya J, Gutierrez Mdel M, Mateo MG, Domingo JC, Giralt M, Villarroya F. Impact of elvitegravir on human adipocytes: alterations in differentiation, gene expression and release of adipokines and cytokines. Antiviral Res. 2016;132:59–65.CrossRef

37.

El Kamari V, Moser C, Hileman CO, Currier JS, Brown TT, Johnston L, Hunt PW, McComsey GA. Lower pretreatment gut integrity is independently associated with fat gain on antiretroviral therapy. Clin Infect Dis. 2019;68(8):1394–401.CrossRef

38.

Tate T, Willig AL, Willig JH, Raper JL, Moneyham L, Kempf M-C, Saag MS, Mugavero MJ. HIV infection and obesity: where did all the wasting go? Antivir Ther. 2012;17(7):1281–9.CrossRef

39.

Hurt CB, Sebastian J, Hicks CB, Eron JJ. Resistance to HIV integrase strand transfer inhibitors among clinical specimens in the United States, 2009–2012. Clin Infect Dis. 2014;58(3):423–31.CrossRef

40.

Mesplède T, Quashie PK, Osman N, Han Y, Singhroy DN, Lie Y, Petropoulos CJ, Huang W, Wainberg MA. Viral fitness cost prevents HIV-1 from evading dolutegravir drug pressure. Retrovirology. 2013;10:22.CrossRef

41.

Rockstroh JK, DeJesus E, Henry K, Molina JM, Gathe J, Ramanathan S, Wei X, Plummer A, Abram M, Cheng AK, et al. A randomized, double-blind comparison of coformulated elvitegravir/cobicistat/emtricitabine/tenofovir DF vs ritonavir-boosted atazanavir plus coformulated emtricitabine and tenofovir DF for initial treatment of HIV-1 infection: analysis of week 96 results. J Acquir Immune Defic Syndr. 2013;62(5):483–6.CrossRef

42.

Raffi F, Rachlis A, Stellbrink HJ, Hardy WD, Torti C, Orkin C, Bloch M, Podzamczer D, Pokrovsky V, Pulido F, et al. Once-daily dolutegravir versus raltegravir in antiretroviral-naive adults with HIV-1 infection: 48 week results from the randomised, double-blind, non-inferiority SPRING-2 study. Lancet. 2013;381(9868):735–43.CrossRef

43.

Gallant J, Lazzarin A, Mills A, Orkin C, Podzamczer D, Tebas P, Girard P-M, Brar I, Daar ES, Wohl D. Bictegravir, emtricitabine, and tenofovir alafenamide versus dolutegravir, abacavir, and lamivudine for initial treatment of HIV-1 infection (GS-US-380-1489): a double-blind, multicentre, phase 3, randomised controlled non-inferiority trial. Lancet. 2017;390(10107):2063–72.CrossRef

Title: Effects of different integrase strand transfer inhibitors on body weight in patients with HIV/AIDS: a network meta-analysis
Authors: Ruojing Bai
Shiyun Lv
Hao Wu
Lili Dai
Publication date: 01-12-2022
Publisher: BioMed Central
Keywords: Human Immunodeficiency Virus
Acquired Immune Deficiency Syndrome
Dolutegravir
Published in: BMC Infectious Diseases / Issue 1/2022
Electronic ISSN: 1471-2334
DOI: https://doi.org/10.1186/s12879-022-07091-1

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