title: PEPDar: A randomized prospective noninferiority study of ritonavir-boosted darunavir for HIV post-exposure prophylaxis.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  Noninferiority of DRV/r to SOC was demonstrated. DRV/r should be included as a standard component of recommended regimens in PEP guidelines.
authors.affiliation: Department I of Internal Medicine, University Hospital of Cologne, Cologne, Germany.|German Centre for Infection Research, partner site Bonn-Cologne, Cologne, Germany.
authors.forename: G
authors.initials: G
authors.lastname: Fätkenheuer
authors.affiliation: Praxis Jessen2 + Kollegen, Berlin, Germany.
authors.forename: H
authors.initials: H
authors.lastname: Jessen
authors.affiliation: ifi - Institute for Interdisciplinary Medicine, Study Centre St. Georg, Hamburg, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Stoehr
authors.affiliation: Department I of Internal Medicine, University Hospital of Cologne, Cologne, Germany.
authors.forename: N
authors.initials: N
authors.lastname: Jung
authors.affiliation: Praxis Jessen2 + Kollegen, Berlin, Germany.
authors.forename: A B
authors.initials: AB
authors.lastname: Jessen
authors.affiliation: Department I of Internal Medicine, University Hospital of Cologne, Cologne, Germany.
authors.forename: T
authors.initials: T
authors.lastname: Kümmerle
authors.affiliation: Immunology Outpatient Clinic, Vivantes Auguste Viktoria Hospital, Berlin, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Berger
authors.affiliation: Section Infectcious Diseases, Med IV, University Hospital of Munich, Munich, Germany.
authors.forename: J R
authors.initials: JR
authors.lastname: Bogner
authors.affiliation: Department of Medicine II, University Hospital Klinikum rechts der Isar, Munich, Germany.
authors.forename: C D
authors.initials: CD
authors.lastname: Spinner
authors.affiliation: Department of Medicine, Center for Internal Medicine, J. W. Goethe-University Frankfurt, Frankfurt am Main, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Stephan
authors.affiliation: Outpatient Infectious Diseases Unit, University Center Hamburg Eppendorf, Hamburg, Germany.
authors.forename: O
authors.initials: O
authors.lastname: Degen
authors.affiliation: Department of Internal Medicine, Medical Clinic II, Ruprecht-Karls-University Heidelberg, Mannheim, Germany.
authors.forename: R
authors.initials: R
authors.lastname: Vogelmann
authors.affiliation: University Hospital Karl Gustav Carus, Dresden, Germany.
authors.forename: P
authors.initials: P
authors.lastname: Spornraft-Ragaller
authors.affiliation: Infectomed, Stuttgart, Germany.
authors.forename: E
authors.initials: E
authors.lastname: Schnaitmann
authors.affiliation: Department of Gastroenterology, Hepatology and Infectiology, University Hospital Düsseldorf, Düsseldorf, Germany.
authors.forename: B
authors.initials: B
authors.lastname: Jensen
authors.affiliation: Group Practice Ulmer/Frietsch/Müller/Roll, Stuttgart, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Ulmer
authors.affiliation: Medical Clinic and Outpatient Clinic I, University Hospital Mainz, Mainz, Germany.
authors.forename: J M
authors.initials: JM
authors.lastname: Kittner
authors.affiliation: Clinic for Internal Medizin III, Ulm University Medical Center, Ulm, Germany.
authors.forename: G
authors.initials: G
authors.lastname: Härter
authors.affiliation: Clinic for Gastroenterology, Hepatology and Infectiology, University Hospital Magdeburg, Magdeburg, Germany.
authors.forename: P
authors.initials: P
authors.lastname: Malfertheiner
authors.affiliation: Internal Medicine I, Gastroenterology, Infectious Diseases, University Hospital Bonn, Bonn, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Rockstroh
authors.affiliation: Internal Medicine Specialist Center Stresemannallee, Frankfurt am Main, Germany.
authors.forename: G
authors.initials: G
authors.lastname: Knecht
authors.affiliation: Practice Hohenstaufenring, Cologne, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Scholten
authors.affiliation: Department of Medicine 3, University Medicine Erlangen, Erlangen, Germany.
authors.forename: T
authors.initials: T
authors.lastname: Harrer
authors.affiliation: Division of Infectious Diseases, University Hospital, Freiburg, Germany.
authors.forename: W V
authors.initials: WV
authors.lastname: Kern
authors.affiliation: Department Internal Medicine I, University Regensburg, Regensburg, Germany.
authors.forename: B
authors.initials: B
authors.lastname: Salzberger
authors.affiliation: Division of Infectiology and Pneumonology, Medical Department, Charité-University Medicine Berlin, Berlin, Germany.
authors.forename: D
authors.initials: D
authors.lastname: Schürmann
authors.affiliation: Janssen-Cilag, Neuss, Germany.
authors.forename: B
authors.initials: B
authors.lastname: Ranneberg
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage* / Q000009:adverse effects*; D000069454:Darunavir / Q000008:administration & dosage* / Q000009:adverse effects*; D005260:Female; D005858:Germany; D006801:Humans; D008297:Male; D056990:Post-Exposure Prophylaxis / Q000379:methods*; D011446:Prospective Studies; D019438:Ritonavir / Q000008:administration & dosage* / Q000009:adverse effects*; D016896:Treatment Outcome; D028761:Withholding Treatment
chemical_list: D019380:Anti-HIV Agents; D019438:Ritonavir; D000069454:Darunavir
keywords: darunavir; lopinavir; occupational exposure; post-exposure prophylaxis; sexual exposure