A clinical review of HIV integrase strand transfer inhibitors (INSTIs) for the prevention and treatment of HIV-1 infection

WHO Guidelines Approved by the Guidelines Review Committee. In Consolidated guidelines on HIV prevention, testing, treatment, service delivery and monitoring: recommendations for a public health approach. Geneva: World Health Organization; 2021.

Google Scholar 

Guidelines for the use of antiretroviral agents in adults and adolescents with HIV [https://clinicalinfo.hiv.gov/sites/default/files/inline-files/AdultandAdolescentGL.pdf]

British HIV. Association (BHIVA) guidelines for the treatment of HIV-infected adults with antiretroviral therapy. HIV Med. 2001;2:276–313.

Article  Google Scholar 

EACS Guidelines version 11.0. October 2021.

Molina JM, Clotet B, van Lunzen J, Lazzarin A, Cavassini M, Henry K, Kulagin V, Givens N, Brennan C, de Oliveira CF. Once-daily dolutegravir is superior to once-daily darunavir/ritonavir in treatment-naive HIV-1-positive individuals: 96 week results from FLAMINGO. J Int AIDS Soc. 2014;17:19490.

Article  PubMed  PubMed Central  Google Scholar 

Raffi F, Jaeger H, Quiros-Roldan E, Albrecht H, Belonosova E, Gatell JM, Baril JG, Domingo P, Brennan C, Almond S, Min S. Once-daily dolutegravir versus twice-daily raltegravir in antiretroviral-naive adults with HIV-1 infection (SPRING-2 study): 96 week results from a randomised, double-blind, non-inferiority trial. Lancet Infect Dis. 2013;13:927–35.

Article  CAS  PubMed  Google Scholar 

Viani RM, Alvero C, Fenton T, Acosta EP, Hazra R, Townley E, Steimers D, Min S, Wiznia A. Safety, pharmacokinetics and efficacy of dolutegravir in treatment-experienced HIV-1 infected adolescents: forty-eight-week results from IMPAACT P1093. Pediatr Infect Dis J. 2015;34:1207–13.

Article  PubMed  PubMed Central  Google Scholar 

Walmsley S, Baumgarten A, Berenguer J, Felizarta F, Florence E, Khuong-Josses MA, Kilby JM, Lutz T, Podzamczer D, Portilla J, et al. Brief report: dolutegravir plus abacavir/lamivudine for the treatment of HIV-1 infection in antiretroviral therapy-naive patients: week 96 and week 144 results from the single randomized clinical trial. J Acquir Immune Defic Syndr. 2015;70:515–9.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Kassahun K, McIntosh I, Cui D, Hreniuk D, Merschman S, Lasseter K, Azrolan N, Iwamoto M, Wagner JA, Wenning LA. Metabolism and disposition in humans of raltegravir (MK-0518), an anti-AIDS drug targeting the human immunodeficiency virus 1 integrase enzyme. Drug Metab Dispos. 2007;35:1657–63.

Article  CAS  PubMed  Google Scholar 

German P, Liu HC, Szwarcberg J, Hepner M, Andrews J, Kearney BP, Mathias A. Effect of cobicistat on glomerular filtration rate in subjects with normal and impaired renal function. J Acquir Immune Defic Syndr. 2012;61:32–40.

Article  CAS  PubMed  Google Scholar 

DeJesus E, Rockstroh JK, Henry K, Molina JM, Gathe J, Ramanathan S, Wei X, Yale K, Szwarcberg J, White 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;379:2429–38.

Article  CAS  PubMed  Google Scholar 

Xue W, Jin X, Ning L, Wang M, Liu H, Yao X. Exploring the molecular mechanism of cross-resistance to HIV-1 integrase strand transfer inhibitors by molecular dynamics simulation and residue interaction network analysis. J Chem Inf Model. 2013;53:210–22.

Article  CAS  PubMed  Google Scholar 

Lahiri CD, Xu Y, Wang K, Alvarez JA, Sheth AN, O’Halloran J, Spence AB, Tien P, Gustafson DR, Milam J, et al. Weight and body mass index change after switching to integrase inhibitors or tenofovir alafenamide among women living with HIV. AIDS Res Hum Retroviruses. 2021;37:461–7.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Cabenuva [package insert]. Research triangle park, NC: ViiV Healthcare; 2022. https://gskpro.com/content/dam/global/hcpportal/en_US/Prescribing_Information/Cabenuva/pdf/CABENUVA-PI-PIL-IFU2-IFU3.PDF. Accessed 25 July 2022.

Biktarvy [package insert]. Foster City, CA: Gilead; 2021. https://www.gilead.com/~/media/files/pdfs/medicines/hiv/biktarvy/biktarvy_pi.pdf. Accessed 25 July 2022.

Hocqueloux L, Lefeuvre S, Bois J, Valentin C, Brucato S, Alix A, Peyro-Saint-Paul L, Got L, Fournel F, Saint-Carlier E, et al. Bioavailability of solid vs. dissolved vs. crushed single-tablet of bictegravir / emtricitabine / tenofovir alafenamide in HIV negative volunteers: the SOLUBIC study. Poster presented at: 18th European AIDS Conference; October 27–30, 2021; London, United Kingdom. Abstract available at: https://www.abstractserver.com/eacsabstractarchive/. Accessed 26 Sept 2022.

Roa PE, Bazzi R. Crushed bictegravir/emtricitabine/tenofovir alafenamide in a human immunodeficiency virus-positive patient with pancreatic cancer. Int J STD AIDS. 2022;33:97–8.

Article  PubMed  Google Scholar 

Rowe SM, Clary JC, Drummond M, Derrick C, Sanasi K, Bookstaver PB. Increased viral load in a hospitalized patient on treatment with crushed bictegravir/emtricitabine/tenofovir alafenamide: a case report and review of the literature. Am J Health Syst Pharm. 2022;79:1330–6.

Article  PubMed  Google Scholar 

Apretude [package insert]. Research triangle park, NC: ViiV Healthcare; 2021. https://gskpro.com/content/dam/global/hcpportal/en_US/Prescribing_Information/Apretude/pdf/APRETUDE-PI-PIL-IFU.PDF. Accessed 25 July 2022.

Tivicay [package insert] research triangle park NG, 2013.: Tivicay [package insert] Research triangle park, NC: GlaxoSmithKline; 2022. https://gskpro.com/content/dam/global/hcpportal/en_US/Prescribing_Information/Tivicay/pdf/TIVICAY-PI-PIL-IFU.PDF#page=1. Accessed 24 Sept 2022.

Dovato [package insert]. Research triangle park, NC: ViiV healthcare; 2022. https://gskpro.com/content/dam/global/hcpportal/en_US/Prescribing_Information/Dovato/pdf/DOVATO-PI-PIL.PDF. Accessed 24 Sept 2022.

Ruel TD, Acosta EP, Liu JP, Gray KP, George K, Montañez N, Popson S, Buchanan AM, Bartlett M, Dayton D, et al. Pharmacokinetics, safety, tolerability, and antiviral activity of dolutegravir dispersible tablets in infants and children with HIV-1 (IMPAACT P1093): results of an open-label, phase 1–2 trial. Lancet HIV. 2022;9:e332–40.

Article  PubMed  PubMed Central  Google Scholar 

Roskam-Kwint M, Bollen P, Colbers A, Duisenberg-van Essenberg M, Harbers V, Burger D. Crushing of dolutegravir fixed-dose combination tablets increases dolutegravir exposure. J Antimicrob Chemother. 2018;73:2430–4.

Article  CAS  PubMed  Google Scholar 

Moore SE, Huesgen E, Howe Z. Sustained virologic suppression with abacavir, emtricitabine, and crushed dolutegravir and tenofovir alafenamide in a patient with HIV and eosinophilic esophagitis. Int J STD AIDS. 2020;31:285–7.

Article  PubMed  Google Scholar 

Buscemi L. Virological suppression after use of crushed tenofovir–emtricitabine and dolutegravir tablets in a patient with HIV infection. Am J Health Syst Pharm. 2016;73:1125–6.

Article  CAS  PubMed  Google Scholar 

Juluca [package insert]. Research Triangle Park, NC: ViiV Healthcare; 2022. https://gskpro.com/content/dam/global/hcpportal/en_US/Prescribing_Information/Juluca/pdf/JULUCA-PI-PIL.PDF#page=1. Accessed 24 Sept 2022.

Triumeq [package insert] Research Triangle Park, NC: ViiV Healthcare; 2022. https://gskpro.com/content/dam/global/hcpportal/en_US/Prescribing_Information/Triumeq/pdf/TRIUMEQ-PI-MG-IFU.PDF#page=1. Accessed 24 Sept 2022.

Genvoya [package insert] Foster City, CA: Gilead Sciences, Inc; 2022. https://www.gilead.com/~/media/files/pdfs/medicines/hiv/genvoya/genvoya_pi.pdf. Accessed 24 Sept 2022.

Fulco PP, Ayala-Sims VA. Sustained virological response after taking crushed elvitegravir-cobicistat-emtricitabine-tenofovir tablets. Am J Health Syst Pharm. 2014;71(784):786.

Google Scholar 

Kaplun O, Psevdos G. Sustained HIV virologic suppression with crushed combination tablets containing elvitegravir, cobicistat, emtricitabine, and tenofovir alafenamide. Am J Health Syst Pharm. 2019;76:1180–1.

Article  PubMed  Google Scholar 

Jongbloed-de Hoon M, Colbers A, Velthoven-Graafland K, Duisenberg-van Essenberg M, Kruijssen M, Abbink E, van Crevel R, Burger D. Brief report: pharmacokinetics of crushed elvitegravir combination tablet given with or without enteral nutrition. J Acquir Immune Defic Syndr. 2017;74:571–4.

Article  CAS  PubMed  Google Scholar 

Stribild [package insert] Foster City, CA: Gilead Sciences; 2021. https://www.gilead.com/~/media/files/pdfs/medicines/hiv/genvoya/genvoya_pi.pdf. Accessed 25 July 2022.

Isentress [package insert] Rahway, NJ: Merck & Co, Inc; 2022. https://www.merck.com/product/usa/pi_circulars/i/isentress/isentress_pi.pdf. Accessed 25 July 2022.

Akil B, Blick G, Haggins DP, Ramgopal MN, Richmond GJ, Samuel RM, Givens N, Vavro C, Song IH, Wynne B. Ait-Khaled M: dolutegravir versus placebo in subjects harbouring HIV-1 with integrase inhibitor resistance associated substitutions: 48-week results from VIKING-4, a randomized study. Antiviral Therapy. 2015;20:343–8.

Article  CAS  PubMed  Google Scholar 

Hawkins KL, Montague BT, Rowan SE, Beum R, McLees MP, Johnson S, Gardner EM. Boosted darunavir and dolutegravir dual therapy among a cohort of highly treatment-experienced individuals. Antivir Ther. 2019;24:513–9.

Article  PubMed  Google Scholar 

Davy-Mendez T, Napravnik S, Zakharova O, Wohl DA, Farel CE, Eron JJ. Effectiveness of integrase strand transfer inhibitors among treatment-experienced patients in a clinical setting. AIDS. 2019;33:1187–95.

Article  CAS  PubMed  Google Scholar 

Levy ME, Griffith C, Ellenberger N, Monroe AK, Castel AD, Rakhmanina N. Outcomes of integrase inhibitor-based antiretroviral therapy in a clinical cohort of treatment-experienced children, adolescents, and young adults with HIV infection. Pediatr Infect Dis J. 2020;39:421–8.

Article  PubMed  PubMed Central  Google Scholar 

Castagna A, Ferrara M, Galli L, Comi L, Sterrantino G, Cenderello G, Zaccarelli M, Focà E, Roncadori A, Lazzarin A, Group PS. Long-term efficacy of dolutegravir in treatment-experienced subjects failing therapy with HIV-1 integrase strand inhibitor-resistant virus. J Antimicrob Chemother. 2018;73:177–82.

Google Scholar 

Rossetti B, Fabbiani M, Di Carlo D, Incardona F, Abecasis A, Gomes P, Geretti AM, Seguin-Devaux C, Garcia F, Kaiser R, et al. Effectiveness of integrase strand transfer inhibitors in HIV-infected treatment-experienced individuals across Europe. HIV Med. 2022;23:774–89.

Article  CAS  PubMed  Google Scholar 

Eron JJ, Clotet B, Durant J, Katlama C, Kumar P, Lazzarin A, Poizot-Martin I, Richmond G, Soriano V, Ait-Khaled M, et al. Safety and efficacy of dolutegravir in treatment-experienced subjects with raltegravir-resistant HIV type 1 infection: 24-week results of the VIKING Study. J Infect Dis. 2013;207:740–8.

Article  CAS  PubMed  Google Scholar 

Espeseth AS, Felock P, Wolfe A, Witmer M, Grobler J, Anthony N, Egbertson M, Melamed JY, Young S, Hamill T, et al. HIV-1 integrase inhibitors that compete with the target DNA substrate define a unique strand transfer conformation for integrase. Proc Natl Acad Sci USA. 2000;97:11244–9.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Hare S, Gupta SS, Valkov E, Engelman A, Cherepanov P. Retroviral intasome assembly and inhibition of DNA strand transfer. Nature. 2010;464:232–6.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Barreca ML, Ferro S, Rao A, De Luca L, Zappalà M, Monforte AM, Debyser Z, Witvrouw M, Chimirri A. Pharmacophore-based design of HIV-1 integrase strand-transfer inhibitors. J Med Chem. 2005;48:7084–8.

Article  CAS  PubMed  Google Scholar 

Smith SJ, Zhao XZ, Passos DO, Pye VE, Cherepanov P, Lyumkis D, Burke TR Jr, Hughes SH. HIV-1 integrase inhibitors with modifications that affect their potencies against drug resistant integrase mutants. ACS Infect Dis. 2021;7:1469–82.

Article  CAS  PubMed  PubMed Central 

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