Long-term safety and impact of immune recovery in heavily treatment-experienced adults receiving fostemsavir for up to 5 years in the phase 3 BRIGHTE study
Llibre Codina, Josep Maria (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Aberg, Judith A. (Icahn School of Medicine at Mount Sinai (Nova York, Estats Units d'Amèrica))
Walmsley, Sharon (University Health Network (Toronto, Canadà))
Velez, Juan (Medicina Interna - Infectología. Fundación Valle del Lili)
Zala, Carlos (Universidad de Buenos Aires)
Crabtree Ramírez, Brenda (Instituto Nacional de Ciencias Médicas y Nutrición)
Shepherd, Bronagh (GSK, Brentford)
Shah, Rimi (ViiV Healthcare)
Clark, Andrew (ViiV Healthcare)
Tenorio, Allan R. (ViiV Healthcare)
Pierce, Amy (ViiV Healthcare)
Du, Fangfang (GlaxoSmithKline)
Li, Bo (GlaxoSmithKline)
Wang, Marcia (GlaxoSmithKline)
Chabria, Shiven (ViiV Healthcare)
Warwick-Sanders, Michael (GlaxoSmithKline)

Data:	2024
Resum:	Introduction: Fostemsavir is a gp120-directed attachment inhibitor approved for heavily treatment-experienced (HTE) adults with multidrug-resistant HIV-1. We provide detailed week 240 safety results from the BRIGHTE study and evaluate the impact of immune recovery on safety outcomes. Methods: The phase 3 BRIGHTE trial is ongoing; data for this analysis were collected from the first participant's first visit (February 23, 2015) through the last participant's last visit for week 240 (March 22, 2021). Safety endpoints were assessed in participants who received fostemsavir + optimized background therapy. In participants with baseline CD4+ T-cell count <200 cells/mm, exposure-adjusted adverse event (AE) rates were assessed among subgroups with or without CD4+ T-cell count ≥200 cells/mm at any time during 48-week analysis periods through week 192. Results: Through a median of 258 weeks (range, 0. 14-319) of treatment, discontinuations due to AEs occurred in 30/371 (8%) participants. Serious AEs were reported in 177/371 (48%) participants, including 16 drug-related events in 13 (4%) participants. Thirty-five (9%) deaths occurred, primarily related to AIDS or acute infections. COVID-19-related events occurred in 25 (7%) participants; all resolved without sequelae. Among participants with baseline CD4+ T-cell count <200 cells/mm, 122/162 (75%) achieved CD4+ T-cell count ≥200 cells/mm at week 192. Exposure-adjusted AE rates were markedly lower among participants achieving CD4+ T-cell count ≥200 cells/mm at any time vs those sustaining <200 cells/mm. No new AIDS-defining events were reported after week 48 in participants with CD4+ T-cell count ≥200 cells/mm. Conclusions: Cumulative safety findings through the BRIGHTE 240-week interim analysis are consistent with other trials in HTE participants with advanced HIV-1 and comorbid disease. Reduced rates of AIDS-defining events and AEs were observed in participants with immunologic recovery on fostemsavir-based treatment. Clinical trial number: NCT02362503, https://clinicaltrials. gov/study/NCT02362503.
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	ARV ; Clinical trials ; Drug resistance ; Intervention ; Treatment
Publicat a:	Frontiers in immunology, Vol. 15 (May 2024) , ISSN 1664-3224

DOI: 10.3389/fimmu.2024.1394644
PMID: 38863717

10 p, 999.0 KB

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