Login Register Cart 0
Generic placeholder image

Current HIV Research

Editor-in-Chief

ISSN (Print): 1570-162X
ISSN (Online): 1873-4251

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Research Article

Comparison of Metabolic Effects of Three Different Treatment Combinations with Retrospective Real-life Data in People Living with HIV

Author(s): Adem Simsek, Oguz Karabay, Ertugrul Guclu and Hande Toptan*

Volume 21, Issue 5, 2023

Published on: 16 November, 2023

Page: [314 - 322] Pages: 9

DOI: 10.2174/011570162X266922231107094649

Price: $65

Abstract

Introduction: Comorbidities are increasing in people living with HIV (PLHIV), and different treatment options have advantages and disadvantages. It is important to compare information from real-life treated cases. The aim of this study was to retrospectively evaluate the data on efficacy and clinical and laboratory findings during different antiretroviral therapies.

Methods: Retrospective file data of 47 PLHIV using Dolutegravir and Lamivudine (3TC/DTG), Tenofovir Alafenamide Emtricitabine and Elvitegravir Cobicistat (EVG/c/TAF/FTC) and Tenofovir Disoproxil Fumarate and Emtricitabine and Efavirenz (EFV/FTC/TDF) were analyzed. Data of the patients at baseline and 12 months after antiretroviral therapy (ART) were compared.

Results: About 47 PLHIV were included in the study. Of the patients, 22 (46.8%) were in the 3TC/DTG group, 19 (40.4%) in the EVG/c/TAF/FTC, and 6 (12.8%) in the EFV/FTC/TDF group. After 12 months of treatment, BMI, HIV-RNA, CD4, WBC, hemoglobin, MCV, PDW, RDW, platelet count, creatinine, eGFR, HDL, AST, glucose values of the 3TC/DTG group were significantly different (p<0.05). After 12 months of treatment, BMI, HIV-RNA, CD4 count, MCV, creatinine, eGFR, HDL, LDL, TG, TC, AST, and HOMA-IR values of the EVG/c/TAF/FTC treatment group were significantly different (p<0.05). After 12 months of treatment, HIV RNA, total bilirubin, and LDL values in the EFV/FTC/TDF treatment group were statistically different (p<0.05).

Conclusion: All treatment groups showed a decrease in HIV-RNA and an increase in CD4 at the end of one year. While CD4 elevation is lower in EFV recipients than in integrase inhibitor (INSTI) recipients, weight gain is higher in INSTI recipients. While the lipid profile was more positively affected in the 3TC/DTG group, lipid profiles were more negatively affected in the EVG/c/TAF/FTC group, although liver and kidney functions were preserved.

Keywords: Antiretroviral therapy, human immunodeficiency virus, metabolic effect, comorbidities.

« Previous Next »
Graphical Abstract

[1]
Deeks SG, Lewin SR, Havlir DV. The end of AIDS: HIV infection as a chronic disease. Lancet 2013; 382(9903): 1525-33.
[http://dx.doi.org/10.1016/S0140-6736(13)61809-7] [PMID: 24152939]
[2]
Kara E, İnkaya AÇ, Aydin Hakli D, Demi̇rkan SK, Ünal S. Polypharmacy and drug-related problems among people living with HIV/AIDS: A single center experience. Turk J Med Sci 2019; 49(1): 222-9.
[http://dx.doi.org/10.3906/sag-1807-295] [PMID: 30761883]
[3]
Taiwo BO, Romdhani H, Lafeuille MH, Bhojwani R, Milbers K, Donga P. Treatment and comorbidity burden among people living with HIV: a review of systematic literature reviews. J Drug Assess 2023; 12(1): 1-11.
[http://dx.doi.org/10.1080/21556660.2022.2149963] [PMID: 36582675]
[4]
Cohen MS, Gay CL. Treatment to prevent transmission of HIV-1. Clin Infect Dis 2010; 50(s3) (3): S85-95.
[http://dx.doi.org/10.1086/651478] [PMID: 20397961]
[5]
Brown AE, Nash S, Connor N, et al. Towards elimination of HIV transmission, AIDS and HIV ‐related deaths in the UK. HIV Med 2018; 19(8): 505-12.
[http://dx.doi.org/10.1111/hiv.12617] [PMID: 29923668]
[6]
Cohen MS, Chen YQ, McCauley M, et al. Antiretroviral therapy for the prevention of HIV-1 transmission. N Engl J Med 2016; 375(9): 830-9.
[http://dx.doi.org/10.1056/NEJMoa1600693] [PMID: 27424812]
[7]
Pascom AR, Pinho REGG, Rick F, et al. Comparison of cumulative viraemia following treatment initiation with different antiretroviral regimens: A real‐life study in Brazil. J Int AIDS Soc 2019; 22(11): e25397.
[http://dx.doi.org/10.1002/jia2.25397] [PMID: 31743620]
[8]
Shah S, Hindley L, Hill A. Are new antiretroviral treatments increasing the risk of weight gain? Drugs 2021; 81(3): 299-315.
[http://dx.doi.org/10.1007/s40265-020-01457-y] [PMID: 33400239]
[9]
Yanai H, Yoshida H. Secondary dyslipidemia: Its treatments and association with atherosclerosis. Global health & medicine 2021; 3(1): 15-23.
[http://dx.doi.org/10.35772/ghm.2020.01078]
[10]
Heron JE, Bagnis CI, Gracey DM. Contemporary issues and new challenges in chronic kidney disease amongst people living with HIV. AIDS Res Ther 2020; 17(1): 11.
[http://dx.doi.org/10.1186/s12981-020-00266-3] [PMID: 32178687]
[11]
Fentaye S, Yibeltal D, Tessema Z. Prevalence of HIV/AIDS among elderly people and associated factors in habru woreda, amhara region. Northeast Ethiopia HIV/AIDS - Research and Palliative Care 2020; 12: 411-23.
[12]
Mellgren Å, Eriksson LE, Reinius M, Marrone G, Svedhem V. Longitudinal trends and determinants of patient-reported side effects on ART–a Swedish national registry study. PLoS One 2020; 15(12): e0242710.
[http://dx.doi.org/10.1371/journal.pone.0242710] [PMID: 33362248]
[13]
Mondi A, Cozzi-Lepri A, Tavelli A, 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.
[http://dx.doi.org/10.1002/jia2.25227] [PMID: 30663278]
[14]
Kim HS, Lee S, Kim JH. Real-world evidence versus randomized controlled trial: Clinical research based on electronic medical records. J Korean Med Sci 2018; 33(34): e213.
[http://dx.doi.org/10.3346/jkms.2018.33.e213] [PMID: 30127705]
[15]
Yeşilbağ Z, Şengül Eİ, Şenoğlu S, Aydın ÖA, Karaosmanoğlu HK. Co-medications and drug-drug interactions in people living with HIV in Turkey in the era of integrase inhibitors. Curr HIV Res 2020; 18(6): 415-25.
[http://dx.doi.org/10.2174/1574885515666200812215140] [PMID: 32787762]
[16]
Ryom L, De Miguel R, Cotter AG, et al. Major revision version 11.0 of the European AIDS clinical society guidelines 2021. HIV Med 2022; 23(8): 849-58.
[http://dx.doi.org/10.1111/hiv.13268] [PMID: 35338549]
[17]
Bennett MD, MACP J, Dolin R, Blaser MJ, Mandell DB. Principles and Practice of Infectious Diseases: 2-Volume Set. Elsevier Health Sciences 2014.
[18]
Isik SA, Gündüz A, Öncül A, Hamidi AA, Sevgi DY, Uzun N, et al. Comparison of antiretroviral therapy regimens with regard to virological and immunological response in treatment-naive hiv/aids patients. Klimik Dergisi/Klimik Journal 2019; 32: 13-8.
[http://dx.doi.org/10.5152/kd.2019.04]
[19]
Buzgan T, Torunoğlu MA, Gökengin D. HIV/AIDS Tanı Tedavi Rehberi. Ankara: Türkiye Halk Sağlığı Kurumu 2013.
[20]
Gumede SB, Venter F, de Wit J, Wensing A, Lalla-Edward ST. Antiretroviral therapy uptake and predictors of virological failure in patients with HIV receiving first-line and second-line regimens in Johannesburg, South Africa: A retrospective cohort data analysis. BMJ Open 2022; 12(4): e054019.
[http://dx.doi.org/10.1136/bmjopen-2021-054019] [PMID: 35428623]
[21]
Edwards JK, Cole SR, Hall HI, et al. Virologic suppression and CD4+ cell count recovery after initiation of raltegravir or efavirenz-containing HIV treatment regimens. AIDS 2018; 32(2): 261-6.
[http://dx.doi.org/10.1097/QAD.0000000000001668] [PMID: 29112076]
[22]
DeJesus E, Rockstroh JK, Henry K, et al. Co-formulated elvitegravir, cobicistat, emtricitabine, and tenofovir disoproxil fumarate versus ritonavir-boosted atazanavir plus co-formulated emtricitabine and tenofovir disoproxil fumarate for initial treatment of HIV-1 infection: A randomised, double-blind, phase 3, non-inferiority trial. Lancet 2012; 379(9835): 2429-38.
[http://dx.doi.org/10.1016/S0140-6736(12)60918-0] [PMID: 22748590]
[23]
Herrera S, Fernandez-Felix BM, Hunt PW, et al. Impact of first-line antiretroviral therapy regimens on the restoration of the CD4/CD8 ratio in the CNICS cohort. J Antimicrob Chemother 2020; 75(6): 1604-10.
[http://dx.doi.org/10.1093/jac/dkaa024] [PMID: 32211777]
[24]
De Salvador-Guillouët F, Sakarovitch C, Durant J, et al. Antiretroviral regimens and CD4/CD8 ratio normalization in hiv-infected patients during the initial year of treatment: A cohort study. PLoS One 2015; 10(10): e0140519.
[http://dx.doi.org/10.1371/journal.pone.0140519] [PMID: 26485149]
[25]
Sax PE, Erlandson KM, Lake JE, et al. Weight gain following initiation of antiretroviral therapy: Risk factors in randomized comparative clinical trials. Clin Infect Dis 2020; 71(6): 1379-89.
[http://dx.doi.org/10.1093/cid/ciz999] [PMID: 31606734]
[26]
Taramasso L, Bonfanti P, Ricci E, et al. Factors associated with weight gain in people treated with dolutegravir. Open Forum Infect Dis 2020; 7(6): ofaa195.
[http://dx.doi.org/10.1093/ofid/ofaa195] [PMID: 32577427]
[27]
Achhra AC, Mocroft A, Reiss P, et al. Short‐term weight gain after antiretroviral therapy initiation and subsequent risk of cardiovascular disease and diabetes: the D : A : D study. HIV Med 2016; 17(4): 255-68.
[http://dx.doi.org/10.1111/hiv.12294] [PMID: 26216031]
[28]
Koethe JR, Heimburger DC. Nutritional aspects of HIV-associated wasting in sub-Saharan Africa. Am J Clin Nutr 2010; 91(4): 1138S-42S.
[http://dx.doi.org/10.3945/ajcn.2010.28608D] [PMID: 20147470]
[29]
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): 1267-74.
[http://dx.doi.org/10.1093/cid/ciz407] [PMID: 31100116]
[30]
Kerchberger AM, Sheth AN, Angert CD, et al. Weight gain associated with integrase stand transfer inhibitor use in women. In Clinical Infectious Diseases 2020; 71(3): 593-600.
[http://dx.doi.org/10.1093/cid/ciz853]
[31]
Menard A, Meddeb L, Tissot-Dupont H, et al. Dolutegravir and weight gain. AIDS 2017; 31(10): 1499-500.
[http://dx.doi.org/10.1097/QAD.0000000000001495] [PMID: 28574967]
[32]
Norwood J, Turner M, Bofill C, et al. Brief report: Weight gain in persons with HIV switched from efavirenz-based to integrase strand transfer inhibitor–based regimens. J Acquir Immune Defic Syndr 2017; 76(5): 527-31.
[http://dx.doi.org/10.1097/QAI.0000000000001525] [PMID: 28825943]
[33]
Bailin SS, Gabriel CL, Fan R, et al. Relationship of subcutaneous adipose tissue inflammation–related gene expression with ectopic lipid deposition in persons with HIV. J Acquir Immune Defic Syndr 2022; 90(2): 175-83.
[http://dx.doi.org/10.1097/QAI.0000000000002926] [PMID: 35125474]
[34]
Buzón-Martín L. Weight gain in HIV-infected individuals using distinct antiretroviral drugs. AIDS Rev 2020; 22(3): 158-67.
[http://dx.doi.org/10.24875/AIDSRev.M20000036] [PMID: 33118531]
[35]
Domingo P, Quesada-López T, Villarroya J, et al. Differential effects of dolutegravir, bictegravir and raltegravir in adipokines and inflammation markers on human adipocytes. Life Sci 2022; 308: 120948.
[http://dx.doi.org/10.1016/j.lfs.2022.120948] [PMID: 36096241]
[36]
McCann K, Shah S, Hindley L, et al. Implications of weight gain with newer anti-retrovirals: 10-year predictions of cardiovascular disease and diabetes. AIDS 2021; 35(10): 1657-65.
[http://dx.doi.org/10.1097/QAD.0000000000002930] [PMID: 33927086]
[37]
Petoumenos K, Kuwanda L, Ryom L, et al. Effect of changes in body mass index on the risk of cardiovascular disease and diabetes mellitus in HIV-positive individuals: Results from the D: A: D study. J Acquir Immune Defic Syndr 2021; 86(5): 579-86.
[http://dx.doi.org/10.1097/QAI.0000000000002603] [PMID: 33351531]
[38]
Kuo PH, Sun HY, Chuang YC, Wu PY, Liu WC, Hung CC. Weight gain and dyslipidemia among virally suppressed HIV-positive patients switching to co-formulated elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide. Int J Infect Dis 2020; 92: 71-7.
[http://dx.doi.org/10.1016/j.ijid.2019.12.029] [PMID: 31884172]
[39]
Squillace N, Ricci E, Menzaghi B, et al. The effect of switching from tenofovir disoproxil fumarate (TDF) to Tenofovir Alafenamide (TAF) on liver enzymes, glucose, and lipid profile. Drug Des Devel Ther 2020; 14: 5515-20.
[http://dx.doi.org/10.2147/DDDT.S274307] [PMID: 33364747]
[40]
Pozniak A, Arribas JR, Gathe J, et al. Switching to tenofovir alafenamide, coformulated with elvitegravir, cobicistat, and emtricitabine, in HIV-Infected Patients With Renal Impairment. J Acquir Immune Defic Syndr 2016; 71(5): 530-7.
[http://dx.doi.org/10.1097/QAI.0000000000000908] [PMID: 26627107]
[41]
Angione SA, Cherian SM, Özdener AE. A review of the efficacy and safety of genvoya® (Elvitegravir, Cobicistat, Emtricitabine, and Tenofovir Alafenamide) in the Management of HIV-1 Infection. J Pharm Pract 2018; 31(2): 216-21.
[http://dx.doi.org/10.1177/0897190017710519] [PMID: 28558493]
[42]
Kileel EM, Lo J, Malvestutto C, et al. Assessment of obesity and cardiometabolic status by integrase inhibitor use in reprieve: A propensity-weighted analysis of a multinational primary cardiovascular prevention cohort of people with human immunodeficiency virus. Open Forum Infect Dis 2021; 8(12): ofab537.
[http://dx.doi.org/10.1093/ofid/ofab537] [PMID: 34888395]
[43]
Cid-Silva P, Fernández-Bargiela N, Margusino-Framiñán L, et al. Treatment with tenofovir alafenamide fumarate worsens the lipid profile of HIV‐infected patients versus treatment with tenofovir disoproxil fumarate, each coformulated with elvitegravir, cobicistat, and emtricitabine. Basic Clin Pharmacol Toxicol 2019; 124(4): 479-90.
[http://dx.doi.org/10.1111/bcpt.13161] [PMID: 30388308]
[44]
Hill A, Waters L, Pozniak A. Are new antiretroviral treatments increasing the risks of clinical obesity? J Virus Erad 2019; 5(1): 41-3.
[http://dx.doi.org/10.1016/S2055-6640(20)30277-6] [PMID: 30800425]
[45]
Domingo P, Villarroya F, Giralt M, Domingo JC. Potential role of the melanocortin signaling system interference in the excess weight gain associated to some antiretroviral drugs in people living with HIV. Int J Obes 2020; 44(9): 1970-3.
[http://dx.doi.org/10.1038/s41366-020-0551-5] [PMID: 32080347]
[46]
Shah S, Hill A. Risks of metabolic syndrome and diabetes with integrase inhibitor-based therapy: Republication. Curr Opin HIV AIDS 2021; 16(2): 106-14.
[http://dx.doi.org/10.1097/COH.0000000000000671] [PMID: 33625041]
[47]
Zakumumpa H, Kitutu FE, Ndagije HB, Diana NK, Ssanyu JN, Kiguba R. Provider perspectives on the acceptability and tolerability of dolutegravir-based anti-retroviral therapy after national roll-out in Uganda: a qualitative study. BMC Infect Dis 2021; 21(1): 1222.
[http://dx.doi.org/10.1186/s12879-021-06933-8] [PMID: 34876050]
[48]
McMahon C, Trevaskis JL, Carter C, et al. Lack of an association between clinical INSTI-related body weight gain and direct interference with MC4 receptor (MC4R), a key central regulator of body weight. PLoS One 2020; 15(2): e0229617.
[http://dx.doi.org/10.1371/journal.pone.0229617] [PMID: 32109250]
[49]
Antunes LC, Elkfury JL, Jornada MN, Foletto KC, Bertoluci MC. Validation of HOMA-IR in a model of insulin-resistance induced by a high-fat diet in Wistar rats. Arch Endocrinol Metab 2016; 60(2): 138-42.
[http://dx.doi.org/10.1590/2359-3997000000169] [PMID: 27191048]
[50]
Muccini C, Galli L, Poli A, et al. Changes in homeostatic model assessment for insulin resistance (HOMA-IR) Index in Treated HIV-1 infected people on virological suppression who switched to a different antiretroviral regimen. J Acquir Immune Defic Syndr 2021; 87(1): e169-73.
[http://dx.doi.org/10.1097/QAI.0000000000002632] [PMID: 33492020]
[51]
Chan L, Asriel B, Eaton EF, Wyatt CM. Potential kidney toxicity from the antiviral drug tenofovir. Curr Opin Nephrol Hypertens 2018; 27(2): 102-12.
[http://dx.doi.org/10.1097/MNH.0000000000000392] [PMID: 29278542]
[52]
Herlitz LC, Mohan S, Stokes MB, Radhakrishnan J, D’Agati VD, Markowitz GS. Tenofovir nephrotoxicity: Acute tubular necrosis with distinctive clinical, pathological, and mitochondrial abnormalities. Kidney Int 2010; 78(11): 1171-7.
[http://dx.doi.org/10.1038/ki.2010.318] [PMID: 20811330]
[53]
Woodward CLN, Hall AM, Williams IG, et al. Tenofovir‐associated renal and bone toxicity. HIV Med 2009; 10(8): 482-7.
[http://dx.doi.org/10.1111/j.1468-1293.2009.00716.x] [PMID: 19459988]
[54]
Waheed S, Attia D, Estrella MM, et al. Proximal tubular dysfunction and kidney injury associated with tenofovir in HIV patients: A case series. Clin Kidney J 2015; 8(4): 420-5.
[http://dx.doi.org/10.1093/ckj/sfv041] [PMID: 26251709]
[55]
Hall AM, Hendry BM, Nitsch D, Connolly JO. Tenofovir-associated kidney toxicity in HIV-infected patients: a review of the evidence. Am J Kidney Dis 2011; 57(5): 773-80.
[http://dx.doi.org/10.1053/j.ajkd.2011.01.022] [PMID: 21435764]
[56]
Casado JL. Renal and bone toxicity with the use of tenofovir: Understanding at the end. AIDS Rev 2016; 18(2): 59-68.
[PMID: 27230467]
[57]
Ueaphongsukkit T, Gatechompol S, Avihingsanon A, et al. Tenofovir alafenamide nephrotoxicity: A case report and literature review. AIDS Res Ther 2021; 18(1): 53.
[http://dx.doi.org/10.1186/s12981-021-00380-w] [PMID: 34419091]
[58]
Hongo H, Nagao T, Nakamura K, et al. Safety and effectiveness analysis of dolutegravir in patients with HIV-1: Interim report of post-marketing surveillance in japan. Adv Ther 2021; 38(8): 4480-504.
[http://dx.doi.org/10.1007/s12325-021-01842-3] [PMID: 34275116]
[59]
Borghetti A, Baldin G, Lombardi F, et al. Efficacy and tolerability of lamivudine plus dolutegravir as a switch strategy in a multicentre cohort of patients with suppressed HIV ‐1 replication. HIV Med 2018; 19(7): 452-4.
[http://dx.doi.org/10.1111/hiv.12611] [PMID: 29573320]
[60]
Metzger IF, Quigg TC, Epstein N, et al. Substantial effect of efavirenz monotherapy on bilirubin levels in healthy volunteers. Curr Ther Res Clin Exp 2014; 76: 64-9.
[http://dx.doi.org/10.1016/j.curtheres.2014.05.002] [PMID: 25352936]
[61]
Estrada V, Monge S, Gómez-Garre MD, et al. Relationship between plasma bilirubin level and oxidative stress markers in HIV ‐infected patients on atazanavir‐ vs. efavirenz‐based antiretroviral therapy. HIV Med 2016; 17(9): 653-61.
[http://dx.doi.org/10.1111/hiv.12368] [PMID: 26935006]
[62]
Poblete D, Bernal F, Llull G, et al. Pharmacogenetic Associations Between Atazanavir/UGT1A1*28 and Efavirenz/rs3745274 (CYP2B6) Account for Specific Adverse Reactions in Chilean Patients Undergoing Antiretroviral Therapy. Front Pharmacol 2021; 12: 660965.
[http://dx.doi.org/10.3389/fphar.2021.660965] [PMID: 34093191]

Rights & Permissions Print Cite
Article Metrics
22
3
World AIDS Vaccine Awareness Day
© 2024 Bentham Science Publishers | Privacy Policy