567
Views
3
CrossRef citations to date
0
Altmetric
Review

Comparative safety review of recommended, first-line single-tablet regimens in patients with HIV

ORCID Icon, ORCID Icon, , &
Pages 1317-1332 | Received 19 Nov 2020, Accepted 12 May 2021, Published online: 27 May 2021

References

  • Antiretroviral therapy cohort collaboration. Survival of HIV-positive patients starting antiretroviral therapy between 1996 and 2013: a collaborative analysis of cohort studies. Lancet HIV. 2017(4):e349–e356
  • Di Biagio A, Cozzi-Lepri A, Prinapori R, et al. Discontinuation of initial antiretroviral therapy in clinical practice: moving toward individualized therapy. J Acquir Immune Defic Syndr. 2016;71:263–271.
  • Kanters S, Vitoria M, Doherty M, et al. Comparative efficacy and safety of first-line antiretroviral therapy for the treatment of HIV infection: a systematic review and network meta-analysis. Lancet HIV. 2016;3:e510–e520.
  • EACS Guidelines, version 10.1. October 2020. [cited 2020 Nov 30]. Available at: https://www.eacsociety.org/files/guidelines-10.1_finaljan2021_1.pdf
  • Panel on antiretroviral guidelines for adults and adolescents. Guidelines for the use of antiretroviral agents in adults and adolescents with HIV. Department Health Human Serv. Available from: https://clinicalinfo.hiv.gov/sites/default/files/guidelines/documents/AdultandAdolescentGL.pdf
  • Astuti N, Single-Tablet MF. Regimens in HIV Therapy. Infect Dis Ther. 2014;3:1–17.
  • Walmsley SL, Antela A, Clumeck N, et al. Dolutegravir plus abacavir-lamivudine for the treatment of HIV-1 infection. N Engl J Med. 2013;369:1807–1818.
  • Raffi F, Rachlis A, Stellbrink H-J, 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;381:735–743.
  • Clotet B, Feinberg J, Van Lunzen J, et al. Once-daily dolutegravir versus darunavir plus ritonavir in antiretroviral-naive adults with HIV-1 infection (FLAMINGO): 48 week results from the randomised open-label phase 3b study. Lancet. 2014;383:2222–2231.
  • Wohl DA, Yazdanpanah Y, Baumgarten A, 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:e355–e363.
  • *Orkin C, DeJesus E, Sax PE, et al. Fixed-dose combination bictegravir, emtricitabine, and tenofovir alafenamide versus dolutegravir-containing regimens for initial treatment of HIV-1 infection: week 144 results from two randomised, double-blind, multicentre, phase 3, non-inferiority trials. Lancet HIV. 2020;7:e389–e400.
  • d’Arminio Monforte A, Cozzi-Lepri A, Di Biagio A, et al. Durability of first-line regimens including integrase strand transfer inhibitors (INSTIs): data from a real-life setting. J Antimicrob Chemother. 2019;74:1363–1367.
  • 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:e25227.
  • Rossetti B, Baldin G, Sterrantino G, et al. Efficacy and safety of dolutegravir-based regimens in advanced HIV-infected naïve patients: results from a multicenter cohort study. Antiviral Res. 2019;169:104552.
  • De Boer MGJ, Van Den Berk GEL, Van Holten N, et al. Intolerance of dolutegravir-containing combination antiretroviral therapy regimens in real-life clinical practice. AIDS. 2016;30:2831–2834.
  • Cid-Silva P, Llibre JM, Fernández-Bargiela N, et al. Clinical experience with the integrase inhibitors Dolutegravir and Elvitegravir in HIV-infected patients: efficacy, safety and tolerance. Basic Clin Pharmacol Toxicol. 2017;121:442–446.
  • Hoffmann C, Welz T, Sabranski M, et al. Higher rates of neuropsychiatric adverse events leading to dolutegravir discontinuation in women and older patients. HIV Med. 2017;18:56–63.
  • Bonfanti P, Madeddu G, Gulminetti R, et al. Discontinuation of treatment and adverse events in an Italian cohort of patients on dolutegravir. AIDS. 2017;31:455–457.
  • Elzi L, Erb S, Furrer H, et al. Adverse events of raltegravir and dolutegravir. AIDS. 2017;31:1853–1858.
  • Peñafiel J, De Lazzari E, Padilla M, et al. Tolerability of integrase inhibitors in a real-life setting. J Antimicrob Chemother. 2017;72:1752–1759.
  • Povar-Echeverría M, Comet-Bernad M, Gasso-Sánchez A, et al. Neuropsychiatric adverse effects of dolutegravir in real-life clinical practice. Enferm Infecc Microbiol Clin. 2021 Feb;39(2):78–82. .
  • Wohl D, Clarke A, Maggiolo F, et al. Patient-reported symptoms over 48 weeks among participants in randomized, double-blind, phase iii non-inferiority trials of adults with hiv on co-formulated bictegravir, emtricitabine, and tenofovir alafenamide versus co-formulated abacavir, dolutegravir, and lamivudine. Patient. 2018;11:561–573.
  • 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;71:1379–1389.
  • Bourgi K, Jenkins CA, Rebeiro PF, 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:e25484.
  • Bourgi K, Rebeiro PF, Turner M, et al. Greater weight gain in treatment-naive persons starting dolutegravir-based antiretroviral therapy. Clin Infect Dis. 2020;70:1267–1274.
  • Taramasso L, Bonfanti P, Ricci E, et al. Factors associated with weight gain in people treated with dolutegravir. Open Forum Infect Dis. 2020;7:ofaa195.
  • Sax P, Althoff KN, Brown TT, et al. Weight change in suppressed people with HIV (PWH) switched from either Tenofovir Disoproxil Fumarate (TDF) or Abacavir (ABC) to Tenofovir Alafenamide (TAF). Open Forum Infect Diseases, Oxford Academic. 2020. p. S846–S847.
  • Gianotti N, Muccini C, Galli L, 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;91:1937–1943.
  • Koteff J, Borland J, Chen S, et al. A phase 1 study to evaluate the effect of dolutegravir on renal function via measurement of iohexol and para-aminohippurate clearance in healthy subjects. Br J Clin Pharmacol. 2013;75:990–996.
  • Reese MJ, Savina PM, Generaux GT, et al. In vitro investigations into the roles of drug transporters and metabolizing enzymes in the disposition and drug interactions of dolutegravir, a HIV integrase inhibitor. Drug Metab Dispos. 2013;41:353–361.
  • Eadon MT, Zhang H, Skaar TC, et al. A two-week regimen of high-dose integrase inhibitors does not cause nephrotoxicity in mice. Antivir Chem Chemother. 2015;24:72–76.
  • McLaughlin MM, Guerrero AJ, Merker A. Renal effects of non-tenofovir antiretroviral therapy in patients living with HIV. Drugs Context. 2018;7:212519.
  • Stricker RB, Man KM, Bouvier DB, et al. Pancreatorenal syndrome associated with combination antiretroviral therapy in HIV infection. Lancet. 1997;349:1745–1746.
  • Nelson M, Azwa A, Sokwala A, et al. Fanconi syndrome and lactic acidosis associated with stavudine and lamivudine therapy. AIDS. 2008;22(11):1374–1376.
  • Morris AA, Baudouin SV, Snow MH. Renal tubular acidosis and hypophosphataemia after treatment with nucleoside reverse transcriptase inhibitors. AIDS. 2001;15:140–141.
  • Taramasso L, Lorenzini P, Di Biagio A, et al. Incidence and risk factors for liver enzyme elevation among naive HIV-1-infected patients receiving ART in the ICONA cohort. J Antimicrob Chemother. 2019;74:3295–3304.
  • Güerri-Fernández R, Molina D, Villar-García J, et al. Brief report: HIV Infection Is associated with worse bone material properties, independently of bone mineral density. J Acquir Immune Defic Syndr. 2016;72:314–318.
  • Carr A, Miller J, Eisman JA, et al. Osteopenia in HIV-infected men: association with asymptomatic lactic acidemia and lower weight pre-antiretroviral therapy. AIDS. 2001;15:703–709.
  • Knobel H, Guelar A, Vallecillo G, et al. Osteopenia in HIV-infected patients: is it the disease or is it the treatment? AIDS. 2001;15:807–808.
  • Woodward CLN, Hall AM, Williams IG, et al. Tenofovir-associated renal and bone toxicity. HIV Med. 2009;10:482–487.
  • Soldado-Folgado J, Lerma-Chippirraz E, Arrieta-Aldea I, et al. Bone density, microarchitecture and tissue quality after 1 year of treatment with dolutegravir/abacavir/lamivudine. J Antimicrob Chemother. 2020;75:2998–3003.
  • Friis-Møller N, Ryom L, Smith C, et al. An updated prediction model of the global risk of cardiovascular disease in HIV-positive persons: the data-collection on adverse effects of anti-HIV drugs (D:A:D) study. Eur J Prev Cardiol. 2016;23:214–223.
  • Hill AM, Mitchell N, Hughes S, et al. Risks of cardiovascular or central nervous system adverse events and immune reconstitution inflammatory syndrome, for dolutegravir versus other antiretrovirals: meta-analysis of randomized trials. Curr Opin HIV AIDS. 2018;13:102–111.
  • Cruciani M, Zanichelli V, Serpelloni G, et al. Abacavir use and cardiovascular disease events: a meta-analysis of published and unpublished data. AIDS. 2011;25:1993–2004.
  • Pham HT, Mesplède T. Bictegravir in a fixed-dose tablet with emtricitabine and tenofovir alafenamide for the treatment of HIV infection: pharmacology and clinical implications. Expert Opin Pharmacother. 2019;20:385–397.
  • Stellbrink H-J, Arribas JR, Stephens JL, 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:e364–e372.
  • Gilead. Biktarvy® (bictegravir, emtricitabine, and tenofovir alafenamide) tablets, for oral use. Initial U.S. Approval. 2018. [Internet]. [cited 2020 Nov 8]. Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210251s000lbl.pdf.
  • Hoffmann C, Schewe K, Fenske S, et al. Short-term neuropsychiatric tolerability of bictegravir combined with emtricitabine/tenofovir alafenamide in clinical practice. Antivir Ther. 2020;25(2):83–90. .
  • Borghetti A, Calcagno A, Lombardi F, et al. SLC22A2 variants and dolutegravir levels correlate with psychiatric symptoms in persons with HIV. J Antimicrob Chemother. 2019;74:1035–1043.
  • Ruane PJ, DeJesus E, Berger D, et al. Antiviral activity, safety, and pharmacokinetics/pharmacodynamics of tenofovir alafenamide as 10-day monotherapy in HIV-1-positive adults. J Acquir Immune Defic Syndr. 2013;63:449–455.
  • Hall AM, Hendry BM, Nitsch D, et al. Tenofovir-associated kidney toxicity in HIV-infected patients: a review of the evidence. Am J Kidney Dis. 2011;57:773–780.
  • Sax PE, Wohl D, Yin MT, et al. Tenofovir alafenamide versus tenofovir disoproxil fumarate, coformulated with elvitegravir, cobicistat, and emtricitabine, for initial treatment of HIV-1 infection: two randomised, double-blind, phase 3, non-inferiority trials. Lancet. 2015;385:2606–2615.
  • Venter WDF, Moorhouse M, Sokhela S, et al. Dolutegravir plus two different prodrugs of tenofovir to treat HIV. N Engl J Med. 2019;381:803–815.
  • LiverTox: Clinical and Research Information on Drug-Induced Liver Injury. Bethesda (MD): national Institute of Diabetes and Digestive and Kidney Diseases; 2012. [cited 2020 Nov 7]. Available from: https://pubmed.ncbi.nlm.nih.gov/31643176/
  • *Wohl D, Oka S, Clumeck N, et al. Brief report: a randomized, double-blind comparison of tenofovir alafenamide versus tenofovir disoproxil fumarate, each coformulated with elvitegravir, cobicistat, and emtricitabine for initial HIV-1 treatment: week 96 results. J Acquir Immune Defic Syndr. 2016;72:58–64.
  • Drug Approval Package: DOVATO – FDA. [cited 2020 Nov 6]. Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/211994s000lbl.pdf.
  • Dovato (dolutegravir/lamivudine): summary of product characteristics; European medicines agency 2019. [cited 2020 Nov 6]. Available from: https://www.ema.europa.eu/en/documents/product-information/dovato-epar-product-information_en.pdf.
  • Cahn P, Rolón MJ, Figueroa MI, et al. Dolutegravir-lamivudine as initial therapy in HIV-1 infected, ARV-naive patients, 48-week results of the PADDLE (Pilot Antiretroviral Design with Dolutegravir LamivudinE) study. J Int AIDS Soc. 2017;20:21678.
  • Taiwo BO, Zheng L, Stefanescu A, et al. ACTG A5353: a pilot study of dolutegravir plus lamivudine for initial treatment of human immunodeficiency virus-1 (HIV-1)-infected participants with HIV-1 RNA <500000 Copies/mL. Clin Infect Dis. 2018;66:1689–1697.
  • Cahn P, Madero JS, Arribas JR, et al. Dolutegravir plus lamivudine versus dolutegravir plus tenofovir disoproxil fumarate and emtricitabine in antiretroviral-naive adults with HIV-1 infection (GEMINI-1 and GEMINI-2): week 48 results from two multicentre, double-blind, randomised, non-inferiority, phase 3 trials. Lancet. 2019;393:143–155.
  • Cahn P, Madero JS, Arribas JR, et al. Durable efficacy of dolutegravir plus lamivudine in antiretroviral treatment-naive adults with HIV-1 infection: 96-week results from the GEMINI-1 and GEMINI-2 randomized clinical trials. J Acquir Immune Defic Syndr. 2020;83:310–318.
  • *Cahn P, Madero JS, Arribas JR, et al. Durable efficacy of dolutegravir (DTG) plus lamivudine (3TC) in antiretroviral treatment-naive adults with HIV-1 infection-3-year results from the GEMINI studies. Abstract from: HIV drug therapy, glasgow 2020. Poster number: P018.
  • Radford M, Parks DC, Ferrante S, et al. Comparative efficacy and safety and dolutegravir and lamivudine in treatment naive HIV patients. AIDS. 2019;33:1739–1749.
  • Ciccullo A, Baldin G, Cossu MV, et al. Dolutegravir plus lamivudine as first-line regimen in a multicenter cohort of HIV-1-infected patients: preliminary data from clinical practice. AIDS Res Hum Retroviruses. 2020;36:4–5.
  • Wang B, Abbott L, Childs K, et al. Dolutegravir-induced liver injury leading to sub-acute liver failure requiring transplantation: a case report and review of literature. Int J STD AIDS. 2018;29:414–417.
  • Wang Y, De Clercq E, Li G. Current and emerging non-nucleoside reverse transcriptase inhibitors (NNRTIs) for HIV-1 treatment. Expert Opin Drug Metab Toxicol. 2019;15:813–829.
  • Molina J-M, Squires K, Sax PE, et al. Doravirine versus ritonavir-boosted darunavir in antiretroviral-naive adults with HIV-1 (DRIVE-FORWARD): 48-week results of a randomised, double-blind, phase 3, non-inferiority trial. Lancet HIV. 2018;5:e211–e220.
  • *Molina J-M, Squires K, Sax PE, et al. Doravirine versus ritonavir-boosted darunavir in antiretroviral-naive adults with HIV-1 (DRIVE-FORWARD): 96-week results of a randomised, double-blind, non-inferiority, phase 3 trial. Lancet HIV. 2020;7:e16–e26.
  • Orkin C, Squires KE, Molina J-M, et al. Doravirine/Lamivudine/Tenofovir Disoproxil Fumarate is non-inferior to Efavirenz/Emtricitabine/Tenofovir Disoproxil Fumarate in treatment-naive adults with human immunodeficiency virus-1 infection: week 48 results of the drive-ahead trial. Clin Infect Dis. 2019;68:535–544.
  • *Orkin C, Squires K, Molina J-M, et al. LB1. Doravirine/Lamivudine/Tenofovir DF Continues to Be NonInferior to Efavirenz/Emtricitabine/Tenofovir DF in Treatment-Naïve Adults With HIV-1 Infection: week 96 Results of the DRIVE-AHEAD Trial. Open Forum Infect Dis. 2018;5:S759.
  • Gatell JM, Morales-Ramirez JO, Hagins DP, et al. Doravirine dose selection and 96-week safety and efficacy versus efavirenz in antiretroviral therapy-naive adults with HIV-1 infection in a Phase IIb trial. Antivir Ther. 2019;24:425–435.
  • Chloe O, Elion R, Thompson M, et al. Changes in weight and body mass index with first-line doravirine-based therapy: a pooled analysis of three randomized controlled trials. AIDS. 2021;35(1):91–99. .
  • Colombier M-A, Molina J-M. Doravirine: a review. Curr Opin HIV AIDS. 2018;13:308–314.
  • Anderson MS, Gilmartin J, Cilissen C, et al. Safety, tolerability and pharmacokinetics of doravirine, a novel HIV non-nucleoside reverse transcriptase inhibitor, after single and multiple doses in healthy subjects. Antivir Ther. 2015;20:397–405.
  • Khalilieh SG, Yee KL, Fan L, et al. A randomized trial to assess the effect of doravirine on the qtc interval using a single supratherapeutic dose in healthy adult volunteers. Clin Drug Investig. 2017;37:975–984.
  • Lacey A, Savinelli S, Barco EA, et al. Investigating the effect of antiretroviral switch to tenofovir alafenamide on lipid profiles in people living with HIV. AIDS. 2020;34:1161–1170.
  • Deeks ED, Deeks ED. Darunavir/Cobicistat/Emtricitabine/Tenofovir Alafenamide: a Review in HIV-1 Infection. Drugs. 2018;78:1013–1024.
  • *Eron JJ, Orkin C, Gallant J, et al. A week-48 randomized phase-3 trial of darunavir/cobicistat/emtricitabine/tenofovir alafenamide in treatment-naive HIV-1 patients. AIDS. 2018;32:1431–1442.
  • Squillace N, Bozzi G, Colella E, et al. Darunavir-cobicistat-emtricitabine-tenofovir alafenamide: safety and efficacy of a protease inhibitor in the modern era. Drug Des Devel Ther. 2018;12:3635–3643.
  • Gomez M, Seybold U, Roider J, et al. A retrospective analysis of weight changes in HIV-positive patients switching from a tenofovir disoproxil fumarate (TDF)- to a tenofovir alafenamide fumarate (TAF)-containing treatment regimen in one German university hospital in 2015-2017. Infection. 2019;47:95–102.
  • Taramasso L, Ricci E, Menzaghi B, et al. Weight Gain: a Possible Side Effect of All Antiretrovirals. Open Forum Infect Dis. 2017;4:ofx239.
  • Capetti A, Cossu MV, Rizzardini G. Darunavir/cobicistat for the treatment of HIV-1: a new era for compact drugs with high genetic barrier to resistance. Expert Opin Pharmacother. 2015;16:2689–2702.
  • Stray KM, Bam RA, Birkus G, et al. Evaluation of the effect of cobicistat on the in vitro renal transport and cytotoxicity potential of tenofovir. Antimicrob Agents Chemother. 2013;57:4982–4989.
  • Auclair M, Afonso P, Capel E, et al. Impact of darunavir, atazanavir and lopinavir boosted with ritonavir on cultured human endothelial cells: beneficial effect of pravastatin. Antivir Ther. 2014;19:773–782.
  • Guaraldi G, Zona S, Cossarizza A, et al. Randomized trial to evaluate cardiometabolic and endothelial function in patients with plasma HIV-1 RNA suppression switching to darunavir/ritonavir with or without nucleoside analogues. HIV Clin Trials. 2013;14:140–148.
  • Ryom L, Lundgren JD, El-Sadr W, et al. Cardiovascular disease and use of contemporary protease inhibitors: the D:A:D international prospective multicohort study. Lancet HIV. 2018;5:e291–e300.
  • Smit M, Cassidy R, Cozzi-Lepri A, et al. Projections of non-communicable disease and health care costs among HIV-positive persons in Italy and the U.S.A.: a modelling study. PLoS One. 2017;12(10):e0186638.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.