G Fätkenheuer1,2, H Jessen3, A Stoehr4, N Jung1, A B Jessen3, T Kümmerle1, M Berger5, J R Bogner6, C D Spinner7, C Stephan8, O Degen9, R Vogelmann10, P Spornraft-Ragaller11, E Schnaitmann12, B Jensen13, A Ulmer14, J M Kittner15, G Härter16, P Malfertheiner17, J Rockstroh18, G Knecht19, S Scholten20, T Harrer21, W V Kern22, B Salzberger23, D Schürmann24, B Ranneberg25. 1. Department I of Internal Medicine, University Hospital of Cologne, Cologne, Germany. 2. German Centre for Infection Research, partner site Bonn-Cologne, Cologne, Germany. 3. Praxis Jessen2 + Kollegen, Berlin, Germany. 4. ifi - Institute for Interdisciplinary Medicine, Study Centre St. Georg, Hamburg, Germany. 5. Immunology Outpatient Clinic, Vivantes Auguste Viktoria Hospital, Berlin, Germany. 6. Section Infectcious Diseases, Med IV, University Hospital of Munich, Munich, Germany. 7. Department of Medicine II, University Hospital Klinikum rechts der Isar, Munich, Germany. 8. Department of Medicine, Center for Internal Medicine, J. W. Goethe-University Frankfurt, Frankfurt am Main, Germany. 9. Outpatient Infectious Diseases Unit, University Center Hamburg Eppendorf, Hamburg, Germany. 10. Department of Internal Medicine, Medical Clinic II, Ruprecht-Karls-University Heidelberg, Mannheim, Germany. 11. University Hospital Karl Gustav Carus, Dresden, Germany. 12. Infectomed, Stuttgart, Germany. 13. Department of Gastroenterology, Hepatology and Infectiology, University Hospital Düsseldorf, Düsseldorf, Germany. 14. Group Practice Ulmer/Frietsch/Müller/Roll, Stuttgart, Germany. 15. Medical Clinic and Outpatient Clinic I, University Hospital Mainz, Mainz, Germany. 16. Clinic for Internal Medizin III, Ulm University Medical Center, Ulm, Germany. 17. Clinic for Gastroenterology, Hepatology and Infectiology, University Hospital Magdeburg, Magdeburg, Germany. 18. Internal Medicine I, Gastroenterology, Infectious Diseases, University Hospital Bonn, Bonn, Germany. 19. Internal Medicine Specialist Center Stresemannallee, Frankfurt am Main, Germany. 20. Practice Hohenstaufenring, Cologne, Germany. 21. Department of Medicine 3, University Medicine Erlangen, Erlangen, Germany. 22. Division of Infectious Diseases, University Hospital, Freiburg, Germany. 23. Department Internal Medicine I, University Regensburg, Regensburg, Germany. 24. Division of Infectiology and Pneumonology, Medical Department, Charité-University Medicine Berlin, Berlin, Germany. 25. Janssen-Cilag, Neuss, Germany.
Abstract
OBJECTIVES: PEPDar compared the tolerability and safety of ritonavir-boosted darunavir (DRV/r)-based post-exposure prophylaxis (PEP) with the tolerability and safety of standard of care (SOC). The primary endpoint was the early discontinuation rate among the per-protocol population. METHODS: PEPDar was an open-label, randomized, multicentre, prospective, noninferiority safety study. Subjects were stratified by type of event (occupational vs. nonoccupational, i.e. sexual) and were randomized to receive DRV/r plus two nucleoside reverse transcriptase inhibitors (NRTIs) or SOC PEP. Twenty-two private or university HIV clinics in Germany participated. Subjects were ≥ 18 years old and had documented or potential HIV exposure and indication for HIV PEP. They initiated PEP not later than 72 h after the event and were HIV negative. RESULTS: A total of 324 subjects were screened, the per-protocol population was 305, and 273 subjects completed the study. One hundred and fifty-five subjects received DRV/r-based PEP and 150 subjects receivedritonavir-boosted lopinavir (LPV/r)-based PEPfor 28-30 days; 298 subjects also receivedtenofovir/emtricitabine. The early discontinuation rate in the DRV/r arm was 6.5% compared with 10.0% in the SOC arm (P = 0.243). Adverse drug reactions (ADRs) were reported in 68% of DRV/r subjects and 75% of SOC subjects (P = 0.169). Fewer DRV/r subjects (16.1%) had at least one grade 2 or 3 ADR compared with SOC subjects (29.3%) (P = 0.006). All grades of diarrhoea, nausea, and sleep disorders were significantly less frequent with DRV/r, while headache was significantly more frequent. No HIV seroconversion was reported during follow-up. CONCLUSIONS: Noninferiority of DRV/r to SOC was demonstrated. DRV/r should be included as a standard component of recommended regimens in PEP guidelines.
RCT Entities:
OBJECTIVES: PEPDar compared the tolerability and safety of ritonavir-boosted darunavir (DRV/r)-based post-exposure prophylaxis (PEP) with the tolerability and safety of standard of care (SOC). The primary endpoint was the early discontinuation rate among the per-protocol population. METHODS: PEPDar was an open-label, randomized, multicentre, prospective, noninferiority safety study. Subjects were stratified by type of event (occupational vs. nonoccupational, i.e. sexual) and were randomized to receive DRV/r plus two nucleoside reverse transcriptase inhibitors (NRTIs) or SOC PEP. Twenty-two private or university HIV clinics in Germany participated. Subjects were ≥ 18 years old and had documented or potential HIV exposure and indication for HIV PEP. They initiated PEP not later than 72 h after the event and were HIV negative. RESULTS: A total of 324 subjects were screened, the per-protocol population was 305, and 273 subjects completed the study. One hundred and fifty-five subjects received DRV/r-based PEP and 150 subjects received ritonavir-boosted lopinavir (LPV/r)-based PEP for 28-30 days; 298 subjects also received tenofovir/emtricitabine. The early discontinuation rate in the DRV/r arm was 6.5% compared with 10.0% in the SOC arm (P = 0.243). Adverse drug reactions (ADRs) were reported in 68% of DRV/r subjects and 75% of SOC subjects (P = 0.169). Fewer DRV/r subjects (16.1%) had at least one grade 2 or 3 ADR compared with SOC subjects (29.3%) (P = 0.006). All grades of diarrhoea, nausea, and sleep disorders were significantly less frequent with DRV/r, while headache was significantly more frequent. No HIV seroconversion was reported during follow-up. CONCLUSIONS: Noninferiority of DRV/r to SOC was demonstrated. DRV/r should be included as a standard component of recommended regimens in PEP guidelines.
Authors: Darrell H S Tan; Mark W Hull; Deborah Yoong; Cécile Tremblay; Patrick O'Byrne; Réjean Thomas; Julie Kille; Jean-Guy Baril; Joseph Cox; Pierre Giguere; Marianne Harris; Christine Hughes; Paul MacPherson; Shannon O'Donnell; Joss Reimer; Ameeta Singh; Lisa Barrett; Isaac Bogoch; Jody Jollimore; Gilles Lambert; Bertrand Lebouche; Gila Metz; Tim Rogers; Stephen Shafran Journal: CMAJ Date: 2017-11-27 Impact factor: 8.262
Authors: Darrell H S Tan; Adrienne K Chan; Peter Jüni; George Tomlinson; Nick Daneman; Sharon Walmsley; Matthew Muller; Rob Fowler; Srinivas Murthy; Natasha Press; Curtis Cooper; Todd Lee; Tony Mazzulli; Allison McGeer Journal: Trials Date: 2021-03-22 Impact factor: 2.279