دورية أكاديمية
Week 240 Efficacy and Safety of Fostemsavir Plus Optimized Background Therapy in Heavily Treatment-Experienced Adults with HIV-1.
| العنوان: | Week 240 Efficacy and Safety of Fostemsavir Plus Optimized Background Therapy in Heavily Treatment-Experienced Adults with HIV-1. |
|---|---|
| المؤلفون: | Aberg JA; Division of Infectious Diseases Mount Sinai Health System, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, Box 1090, New York, NY, 10029, USA. judith.aberg@mssm.edu., Shepherd B; GSK, 980 Great West Road, Brentford, TW8 9GS, Middlesex, UK., Wang M; GSK, 1250 S Collegeville Road, Collegeville, PA, 19426, USA., Madruga JV; CRT-DST/AIDS SP, Rua Santa Cruz 81, Vila Mariana, São Paulo, CEP: 04121-000, Brazil., Mendo Urbina F; Hospital Nacional Edgardo Rebagliati Martins, Av. Edgardo Rebagliati 490, Jesús María, 15072, Peru., Katlama C; Service de Maladies Infectieuses et Tropicales, AP-HP, Hôpital Pitié-Salpêtrière, INSERM-Sorbonne Universités, 47-83 Bd de l'hôpital, 75013, Paris, France., Schrader S; Schrader Clinic, 2211 Norfolk Street #1050, Houston, TX, 77098, USA., Eron JJ; University of North Carolina at Chapel Hill School of Medicine, 321 S Columbia Street, Chapel Hill, NC, 27599, USA., Kumar PN; Georgetown University Medical Center, 37th and O Street, N.W., Washington, DC, 20057, USA., Sprinz E; Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, R. Ramiro Barcelos, 2350 - Santa Cecília, Porto Alegre, RS, 90035-903, Brazil., Gartland M; ViiV Healthcare, 406 Blackwell Street, Suite 300, Durham, NC, 27701, USA., Chabria S; ViiV Healthcare, 36 E Industrial Road, Branford, CT, 06405, USA., Clark A; ViiV Healthcare, 980 Great West Road, Brentford, TW8 9GS, Middlesex, UK., Pierce A; ViiV Healthcare, 406 Blackwell Street, Suite 300, Durham, NC, 27701, USA., Lataillade M; ViiV Healthcare, 36 E Industrial Road, Branford, CT, 06405, USA., Tenorio AR; ViiV Healthcare, 406 Blackwell Street, Suite 300, Durham, NC, 27701, USA. |
| المصدر: | Infectious diseases and therapy [Infect Dis Ther] 2023 Sep; Vol. 12 (9), pp. 2321-2335. Date of Electronic Publication: 2023 Sep 26. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Adis Country of Publication: New Zealand NLM ID: 101634499 Publication Model: Print-Electronic Cited Medium: Print ISSN: 2193-8229 (Print) Linking ISSN: 21936382 NLM ISO Abbreviation: Infect Dis Ther Subsets: PubMed not MEDLINE |
| أسماء مطبوعة: | Publication: 2014- : [Auckland] Adis Original Publication: [London] : Springer Healthcare |
| مستخلص: | Introduction: Efficacy and safety of the attachment inhibitor fostemsavir + optimized background therapy (OBT) were evaluated through 48 and 96 weeks in the phase 3 BRIGHTE trial in heavily treatment-experienced (HTE) adults failing their current antiretroviral regimen. Here, we report 240-week efficacy and safety of fostemsavir + OBT in adults with multidrug-resistant human immunodeficiency virus (HIV)-1 in BRIGHTE. Methods: Heavily treatment-experienced adults failing their current regimen entered the randomized cohort (RC; 1-2 fully active antiretrovirals available) or non-randomized cohort (NRC; no fully active antiretrovirals available) and received open-label fostemsavir + OBT (starting Day 8 in RC and Day 1 in NRC). Endpoints included proportion with virologic response (HIV-1 RNA < 40 copies/mL, Snapshot), immunologic efficacy, and safety. Results: At Week 240, 45% and 22% of the RC and NRC, respectively, had virologic response (Snapshot); 7% of the RC and 5% of the NRC had missing data due to coronavirus disease 2019 (COVID-19)-impacted visits. In the observed analysis, 82% of the RC and 66% of the NRC had virologic response. At Week 240, mean change from baseline in CD4+ T-cell count was 296 cells/mm 3 (RC) and 240 cells/mm 3 (NRC); mean CD4+/CD8+ ratio increased between Weeks 96 and 240 (RC 0.44 to 0.60; NRC 0.23 to 0.32). Between Weeks 96 and 240, four participants discontinued for adverse events, one additional participant experienced a drug-related serious adverse event, and six deaths occurred (median last available CD4+ T-cell count, 3 cells/mm 3 ). COVID-19-related events occurred in 25 out of 371 participants; all resolved without incident. Conclusion: Through ~5 years, fostemsavir + OBT demonstrated durable virologic and immunologic responses with no new safety concerns between Weeks 96 and 240, supporting this regimen as a key therapeutic option for HTE people with multidrug-resistant HIV-1. Trial Registration: ClinicalTrials.gov, NCT02362503. (© 2023. The Author(s).) |
| References: | Open Forum Infect Dis. 2021 Nov 06;8(12):ofab562. (PMID: 34934773) Sci Rep. 2021 Mar 18;11(1):6283. (PMID: 33737527) J Antimicrob Chemother. 2014 Mar;69(3):573-81. (PMID: 24128669) N Engl J Med. 2020 Mar 26;382(13):1232-1243. (PMID: 32212519) Lancet HIV. 2015 Mar;2(3):e98-106. (PMID: 26424550) Lancet Infect Dis. 2013 Jul;13(7):587-96. (PMID: 23664333) Lancet Microbe. 2020 Jul;1(3):e130-e135. (PMID: 35544263) J Antimicrob Chemother. 2020 May 1;75(5):1301-1310. (PMID: 31976521) AIDS. 2022 Jan 1;36(1):11-18. (PMID: 34628442) Antimicrob Agents Chemother. 2012 Jul;56(7):3498-507. (PMID: 22547625) Antivir Ther. 2015;20(3):343-8. (PMID: 25321146) Curr HIV/AIDS Rep. 2022 Oct;19(5):425-432. (PMID: 35930187) J Acquir Immune Defic Syndr. 2018 Mar 1;77(3):299-307. (PMID: 29206721) J Antimicrob Chemother. 2021 Oct 11;76(11):2958-2964. (PMID: 34297843) J Virol. 2014 Oct;88(19):11045-55. (PMID: 25008924) JAMA Netw Open. 2021 Feb 1;4(2):e2037069. (PMID: 33533933) Lancet Infect Dis. 2015 Jul;15(7):810-8. (PMID: 26070969) N Engl J Med. 2018 Aug 16;379(7):645-654. (PMID: 30110589) Antimicrob Agents Chemother. 2013 Sep;57(9):4172-80. (PMID: 23774428) PLoS One. 2017 Mar 27;12(3):e0174550. (PMID: 28346521) Viruses. 2011 May;3(5):586-612. (PMID: 21994747) Lancet HIV. 2020 Nov;7(11):e740-e751. (PMID: 33128903) Antivir Ther. 2010;15(7):1045-52. (PMID: 21041921) Antimicrob Agents Chemother. 2011 Feb;55(2):729-37. (PMID: 21078948) Nat Chem Biol. 2017 Oct;13(10):1115-1122. (PMID: 28825711) J Acquir Immune Defic Syndr. 2013 Sep 1;64(1):7-15. (PMID: 23614999) J Immunol. 2013 Oct 15;191(8):4246-58. (PMID: 24043886) |
| فهرسة مساهمة: | Keywords: Advanced HIV disease; Attachment inhibitor; CD4+/CD8+ ratio; CD4+ T-cell count; Virologic response |
| سلسلة جزيئية: | ClinicalTrials.gov NCT02362503 |
| تواريخ الأحداث: | Date Created: 20230926 Latest Revision: 20231020 |
| رمز التحديث: | 20240628 |
| مُعرف محوري في PubMed: | PMC10581994 |
| DOI: | 10.1007/s40121-023-00870-6 |
| PMID: | 37751019 |
| قاعدة البيانات: | MEDLINE |
Find this article in full text from Springer Verlag. 
Full Text Finder | تدمد: | 2193-8229 |
|---|---|
| DOI: | 10.1007/s40121-023-00870-6 |