Giuliano Rizzardini1,2, Andrea Gori3, Celia Miralles4, Julián Olalla5, Jean-Michel Molina6, François Raffi7, Princy Kumar8, Andrea Antinori9, Moti Ramgopal10, Hans-Jürgen Stellbrink11, Moupali Das12, Hoa Chu12, Renee Ram12, Will Garner12, Yongwu Shao12, Susan K Chuck12, David Piontkowsky12, Richard H Haubrich12. 1. ASST Fatebenefratelli-Sacco, Milan, Italy. 2. School of Clinical Medicine, Faculty of Health Science University of the Witwatersrand, Johannesburg, South Africa. 3. Infectious Diseases Unit, San Gerardo Hospital, Monza, Italy. 4. Complejo Hospitalario Universitario de Vigo, Vigo. 5. Hospital Universitario Cruces, Bilbao, Spain. 6. Department of Infectious Diseases, Saint Louis Hospital, Assistance Publique Hôpitaux de Paris, University Paris Diderot. 7. Department of Infectious Diseases, University Hospital of Nantes and CIC 1413, INSERM, Nantes, France. 8. Division of Infectious Diseases, Georgetown University, Washington, DC, USA. 9. HIV/AIDS Department, National Institute for Infectious Diseases Lazzaro Spallanzani IRCCS, Rome, Italy. 10. Midway Immunology and Research Center, Fort Pierce, Florida, USA. 11. ICH Study Center, Hamburg, Germany. 12. Gilead Sciences, Inc., Foster City, California, USA.
Abstract
OBJECTIVE: To evaluate the efficacy and safety of switching from an abacavir/lamivudine (ABC/3TC)-based regimen to an elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF) single-tablet regimen in virologically suppressed, HIV-1-infected adults. DESIGN: Randomized, open-label, noninferiority study. METHODS:Participants with HIV-1 RNA levels less than 50 copies/ml receiving ABC/3TC plus a third agent for at least 6 months were randomized 2 : 1 to switch immediately to E/C/F/TAF (immediate-switch group) for 48 weeks or to continue receiving ABC/3TC plus a third agent for 24 weeks followed by E/C/F/TAF for 24 weeks (delayed-switch group). The primary endpoint was HIV-1 RNA less than 50 copies/ml at Week 24 by Food and Drug Administration Snapshot algorithm (-12% noninferiority margin). RESULTS: Baseline characteristics of 274 participants (183 in immediate-switch group and 91 in delayed-switch group) were similar. Virologic response was maintained at Week 24 by 93.4 and 97.8% of participants in the immediate-switch and delayed-switch groups, respectively, with a treatment difference of -4.4% (95% confidence interval: -9.4 to 1.9%), confirming noninferiority. Adverse events of any grade were similar between groups through Week 24 (66% E/C/F/TAF, 64% ABC/3TC); adverse event-related drug discontinuations occurred in 4% of participants switching to E/C/F/TAF (no discontinuations because of renal events) and no participants continuing ABC/3TC. Renal biomarkers of urine albumin:creatinine and beta-2-microglobulin:creatinine ratios significantly improved on E/C/F/TAF. Self-reported treatment satisfaction was significantly higher with E/C/F/TAF. CONCLUSION: Switching to E/C/F/TAF was noninferior to continuing ABC/3TC plus a third agent for maintenance of HIV RNA suppression at Week 24. This study supports E/C/F/TAF as an efficacious and well tolerated option for participants switching from ABC/3TC-based regimens.
RCT Entities:
OBJECTIVE: To evaluate the efficacy and safety of switching from an abacavir/lamivudine (ABC/3TC)-based regimen to an elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF) single-tablet regimen in virologically suppressed, HIV-1-infected adults. DESIGN: Randomized, open-label, noninferiority study. METHODS:Participants with HIV-1 RNA levels less than 50 copies/ml receiving ABC/3TC plus a third agent for at least 6 months were randomized 2 : 1 to switch immediately to E/C/F/TAF (immediate-switch group) for 48 weeks or to continue receiving ABC/3TC plus a third agent for 24 weeks followed by E/C/F/TAF for 24 weeks (delayed-switch group). The primary endpoint was HIV-1 RNA less than 50 copies/ml at Week 24 by Food and Drug Administration Snapshot algorithm (-12% noninferiority margin). RESULTS: Baseline characteristics of 274 participants (183 in immediate-switch group and 91 in delayed-switch group) were similar. Virologic response was maintained at Week 24 by 93.4 and 97.8% of participants in the immediate-switch and delayed-switch groups, respectively, with a treatment difference of -4.4% (95% confidence interval: -9.4 to 1.9%), confirming noninferiority. Adverse events of any grade were similar between groups through Week 24 (66% E/C/F/TAF, 64% ABC/3TC); adverse event-related drug discontinuations occurred in 4% of participants switching to E/C/F/TAF (no discontinuations because of renal events) and no participants continuing ABC/3TC. Renal biomarkers of urine albumin:creatinine and beta-2-microglobulin:creatinine ratios significantly improved on E/C/F/TAF. Self-reported treatment satisfaction was significantly higher with E/C/F/TAF. CONCLUSION: Switching to E/C/F/TAF was noninferior to continuing ABC/3TC plus a third agent for maintenance of HIV RNA suppression at Week 24. This study supports E/C/F/TAF as an efficacious and well tolerated option for participants switching from ABC/3TC-based regimens.
Authors: Ignacio Perez Valero; Alfonso Cabello; Pablo Ryan; Sara De La Fuente-Moral; Ignacio Santos; Maria Jesus Vivancos; Alicia Gonzalez; Miguel Gorgolas; Guillermo Cuevas; Alberto Diaz De Santiago; Joanna Cano; Guadalupe Rua; Maria Yllescas; Juan Julian González García Journal: Open Forum Infect Dis Date: 2020-10-18 Impact factor: 3.835