Peter Ackerman1, Melanie Thompson2, Jean-Michel Molina3, Judith Aberg4, Isabel Cassetti5, Michael Kozal6, Antonella Castagna7, Marcelo Martins8, Moti Ramgopal9, Eduardo Sprinz10, Sandra Treviño-Pérez11, Adrian Streinu-Cercel12, Gulam H Latiff13, Gilles Pialoux14, Princy N Kumar15, Marcia Wang16, Shiven Chabria1, Amy Pierce17, Cyril Llamoso1, Max Lataillade1. 1. ViiV Healthcare, Branford, Connecticut. 2. AIDS Research Consortium of Atlanta, Atlanta, Georgia, USA. 3. Hospital Saint-Louis/Lariboisière, Assistance Publique hopitaux de Paris, Université de Paris, INSERM U944, Paris, France. 4. Icahn School of Medicine at Mount Sinai, New York, New York, USA. 5. Helios Salud, AIDS Care Center Infectious Diseases, Buenos Aires, Argentina. 6. Yale University School of Medicine and VA Connecticut Healthcare System, New Haven, Connecticut, USA. 7. IRCCS San Raffaele Hospital and Vita-Salute San Raffaele University, Milan, Italy. 8. Instituto Oulton, Cordoba, Argentina. 9. Midway Specialty Care Center, Fort Pierce, Florida, USA. 10. Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil. 11. Mexico Centre for Clinical Research, Mexico City, Mexico. 12. National Institute of Infectious Diseases 'Prof. Dr. Matei Balş,' Bucharest, Romania. 13. Maxwell Centre, Durban, South Africa. 14. Hôpital Tenon, Assistance Publique Hôpitaux de Paris, Paris, France. 15. Georgetown University School of Medicine, Washington, District of Columbia. 16. GlaxoSmithKline, Upper Providence, Pennsylvania. 17. ViiV Healthcare, Research Triangle Park, North Carolina, USA.
Abstract
OBJECTIVES: The aim of this study was to understand how demographic and treatment-related factors impact responses to fostemsavir-based regimens. DESIGN: BRIGHTE is an ongoing phase 3 study evaluating twice-daily fostemsavir 600 mg and optimized background therapy (OBT) in heavily treatment-experienced individuals failing antiretroviral therapy with limited treatment options (Randomized Cohort 1-2 and Nonrandomized Cohort 0 fully active antiretroviral classes). METHODS: Virologic response rates (HIV-1 RNA <40 copies/ml, Snapshot analysis) and CD4+ T-cell count increases in the Randomized Cohort were analysed by prespecified baseline characteristics (age, race, sex, region, HIV-1 RNA, CD4+ T-cell count) and viral susceptibility to OBT. Safety results were analysed by baseline characteristics for combined cohorts (post hoc). RESULTS: In the Randomized Cohort, virologic response rates increased between Weeks 24 and 96 across most subgroups. Virologic response rates over time were most clearly associated with overall susceptibility scores for new OBT agents (OSS-new). CD4+ T-cell count increases were comparable across subgroups. Participants with baseline CD4+ T-cell counts less than 20 cells/μl had a mean increase of 240 cells/μl. In the safety population, more participants with baseline CD4+ T-cell counts less than 20 vs. at least 200 cells/μl had grade 3/4 adverse events [53/107 (50%) vs. 24/96 (25%)], serious adverse events [58/107 (54%) vs. 25/96 (26%)] and deaths [16/107 (15%) vs. 2/96 (2%)]. There were no safety differences by other subgroups. CONCLUSION: Week 96 results for BRIGHTE demonstrate comparable rates of virologic and immunologic response (Randomized Cohort) and safety (combined cohorts) across subgroups. OSS-new is an important consideration when constructing optimized antiretroviral regimens for heavily treatment-experienced individuals with limited remaining treatment options.
OBJECTIVES: The aim of this study was to understand how demographic and treatment-related factors impact responses to fostemsavir-based regimens. DESIGN: BRIGHTE is an ongoing phase 3 study evaluating twice-daily fostemsavir 600 mg and optimized background therapy (OBT) in heavily treatment-experienced individuals failing antiretroviral therapy with limited treatment options (Randomized Cohort 1-2 and Nonrandomized Cohort 0 fully active antiretroviral classes). METHODS: Virologic response rates (HIV-1 RNA <40 copies/ml, Snapshot analysis) and CD4+ T-cell count increases in the Randomized Cohort were analysed by prespecified baseline characteristics (age, race, sex, region, HIV-1 RNA, CD4+ T-cell count) and viral susceptibility to OBT. Safety results were analysed by baseline characteristics for combined cohorts (post hoc). RESULTS: In the Randomized Cohort, virologic response rates increased between Weeks 24 and 96 across most subgroups. Virologic response rates over time were most clearly associated with overall susceptibility scores for new OBT agents (OSS-new). CD4+ T-cell count increases were comparable across subgroups. Participants with baseline CD4+ T-cell counts less than 20 cells/μl had a mean increase of 240 cells/μl. In the safety population, more participants with baseline CD4+ T-cell counts less than 20 vs. at least 200 cells/μl had grade 3/4 adverse events [53/107 (50%) vs. 24/96 (25%)], serious adverse events [58/107 (54%) vs. 25/96 (26%)] and deaths [16/107 (15%) vs. 2/96 (2%)]. There were no safety differences by other subgroups. CONCLUSION: Week 96 results for BRIGHTE demonstrate comparable rates of virologic and immunologic response (Randomized Cohort) and safety (combined cohorts) across subgroups. OSS-new is an important consideration when constructing optimized antiretroviral regimens for heavily treatment-experienced individuals with limited remaining treatment options.
Authors: Margaret Gartland; Pedro Cahn; Edwin DeJesus; Ricardo Sobhie Diaz; Robert Grossberg; Michael Kozal; Princy Kumar; Jean-Michel Molina; Fernando Mendo Urbina; Marcia Wang; Fangfang Du; Shiven Chabria; Andrew Clark; Louise Garside; Mark Krystal; Frank Mannino; Amy Pierce; Peter Ackerman; Max Lataillade Journal: Antimicrob Agents Chemother Date: 2022-05-03 Impact factor: 5.938