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. 2023 Sep;12(9):2321-2335.
doi: 10.1007/s40121-023-00870-6. Epub 2023 Sep 26.

Week 240 Efficacy and Safety of Fostemsavir Plus Optimized Background Therapy in Heavily Treatment-Experienced Adults with HIV-1

Judith A Aberg  1 , Bronagh Shepherd  2 , Marcia Wang  3 , Jose V Madruga  4 , Fernando Mendo Urbina  5 , Christine Katlama  6 , Shannon Schrader  7 , Joseph J Eron  8 , Princy N Kumar  9 , Eduardo Sprinz  10 , Margaret Gartland  11 , Shiven Chabria  12 , Andrew Clark  13 , Amy Pierce  11 , Max Lataillade  12 , Allan R Tenorio  11
Affiliations

Week 240 Efficacy and Safety of Fostemsavir Plus Optimized Background Therapy in Heavily Treatment-Experienced Adults with HIV-1

Judith A Aberg et al. Infect Dis Ther. 2023 Sep.

Abstract

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/mm3 (RC) and 240 cells/mm3 (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/mm3). 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.

Keywords: Advanced HIV disease; Attachment inhibitor; CD4+/CD8+ ratio; CD4+ T-cell count; Virologic response.

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Conflict of interest statement

Judith A. Aberg has received grants from Emergent BioSolutions, Frontier Technologies, Gilead, GSK, Janssen, Merck, Pfizer, Regeneron, and ViiV Healthcare, which were paid to her institution, and participated in scientific advisory boards for GSK, Merck, and ViiV Healthcare. Bronagh Shepherd and Marcia Wang are employees of and may own stock in GSK. Jose V. Madruga has received grants for participation in scientific advisory boards from Gilead, GSK, Janssen, MSD, and ViiV Healthcare; sponsorship to attend international congresses from Gilead and Janssen; personal fees for lectures from Gilead, GSK, Janssen, MSD, Pfizer, and ViiV Healthcare; and has served as an investigator in clinical trials sponsored by Gilead, GSK, Janssen, MSD, Pfizer, Sanofi, and ViiV Healthcare. Fernando Mendo Urbina has received honoraria from Johnson and Johnson. Christine Katlama has received grants and/or personal fees from ViiV Healthcare, Gilead, and MSD. Shannon Schrader has received honoraria from Gilead and Janssen. Joseph J. Eron has received grants from Gilead, Janssen, and ViiV Healthcare, which were paid to his institution, and consultant fees from Gilead, Merck, and ViiV Healthcare. Princy N. Kumar has received grants from Eli Lilly, GSK, Merck, Gilead, Regeneron, American Gene Technologies, and BioHaven, which were paid to her institution; participated in data safety monitoring/advisory boards for Johnson & Johnson, ViiV Healthcare, Gilead, TheraTechnologies, and Merck; and holds stock/stock options in Merck, Johnson & Johnson, GSK, Gilead, Pfizer, and Moderna. Eduardo Sprinz has received grants for participation in scientific advisory boards from Abbott, Gilead, GSK, Janssen, MSD, Roche, and ViiV Healthcare. Margaret Gartland, Shiven Chabria, Andrew Clark, Amy Pierce, Max Lataillade, and Allan R. Tenorio are employees of ViiV Healthcare and may own stock in GSK.

Figures

Fig. 1
Fig. 1
Study design. ARV antiretroviral, BID twice daily, FTR fostemsavir, HTE heavily treatment-experienced, OBT optimized background therapy. aThere were no screening temsavir susceptibility criteria. bFully active is based on susceptibility (current or historical resistance measures) and availability [the participant is tolerant of, eligible for, and willing to take (in the case of enfuvirtide only) the ARV]. cUse of investigational agents as part of OBT was permitted in the non-randomized cohort only. dSubsequent time points were measured from the start of open-label FTR 600 mg BID + OBT. eThe study is expected to be conducted until participants can access FTR through other means (e.g., marketing approval). fLast study participant first dose. gDatabase lock June 2021
Fig. 2
Fig. 2
Virologic response (HIV-1 RNA < 40 copies/mL) through Week 240 by Snapshot analysis (ITT-E) and observed analysis. ITT-E participants without an HIV-1 RNA value at the relevant time point or those who changed OBT due to lack of efficacy up to each time point counted as failures. ITT-E intention-to-treat exposed, OBT optimized background therapy. aITT-E population, N = 267. bITT-E population, N = 92
Fig. 3
Fig. 3
a Change in CD4+ T-cell count from baseline to Week 240 and b CD4+/CD8+ ratio through Week 240 (observed analysis). Baseline mean (SD): CD4+ T-cell count, RC 152.5 (182.0) and NRC 99.4 (130.8) cells/mm3; CD4+/CD8+ ratio, RC 0.20 (0.24) and 0.12 (0.12). Error bars represent standard deviation
See this image and copyright information in PMC

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