title: Effect of Pritelivir Compared With Valacyclovir on Genital HSV-2 Shedding in Patients With Frequent Recurrences: A Randomized Clinical Trial.
abstract: Current therapy of herpes infections relies on nucleoside analogues. Pritelivir is a well-tolerated novel herpes simplex virus (HSV) helicase-primase inhibitor that reduced genital shedding and lesions.
  
  
  
  To compare the efficacy of pritelivir with valacyclovir for suppression of genital HSV-2 infection.
  
  
  
  A phase 2, randomized, double-blind, crossover clinical trial at clinical research centers in 4 US cities (October 2012-July 2013) compared daily oral doses of 100 mg of pritelivir with 500 mg of valacyclovir. The planned sample size was 98 adults, allowing for detection of a 50% reduction in viral shedding between the study treatments. Healthy adults with 4 to 9 annual genital HSV-2 recurrences were eligible.  45 participants were randomized to receive pritelivir [corrected]  and 46 to receive valacyclovir first when the US Food and Drug Administration placed the trial on clinical hold based on findings in a concurrent nonclinical toxicity study, and the sponsor terminated the study.
  
  
  
  Participants took the first drug for 28 days followed by 28 days of washout before taking the second drug for 28 days. Throughout treatment, the participants collected genital swabs 4 times daily for testing by HSV polymerase chain reaction assays.
  
  
  
  The primary end point was within-participant genital HSV shedding while receiving pritelivir compared with valacyclovir. Secondary end points included the quantity of HSV in positive swabs and the frequency of genital lesions and shedding episodes.
  
  
  
  Of the 91 randomized participants (median age, 48 years; 57 women [63%]), 56 had completed both treatment periods at the time of the study's termination. In intent-to-treat analyses, HSV shedding was detected in 2.4% (173 of 7276 ) of swabs during pritelivir treatment compared with 5.3% (392 of 7453) during valacyclovir treatment (relative risk [RR], 0.42 [corrected]; 95% CI, 0.21 to 0.82; P = .01). In swabs with HSV, the mean quantity of HSV was 3.2 log10 copies/mL during pritelivir treatment vs 3.7 log10 copies/mL during valacyclovir treatment (difference, -0.1; 95% CI, -0.6 to 0.5; P = .83). Genital lesions were present on 1.9% of days in the pritelivir group vs 3.9% in the valacyclovir group (RR, 0.40; 95% CI, 0.17-0.96; P = .04). The frequency of shedding episodes did not differ by group, with 1.3 per person-month for pritelivir and 1.6 per person-month for valacyclovir (RR, 0.80; 95% CI, 0.52 to 1.22; P = .29). Treatment-emergent adverse events occurred in 62.3% of participants in the pritelivir group and 69.2% of participants in the valacyclovir group.
  
  
  
  Among adults with frequently recurring genital HSV-2, the use of pritelivir compared with valacyclovir resulted in a lower percentage of swabs with HSV detection over 28 days. Further research is needed to assess longer-term efficacy and safety.
  
  
  
  clinicaltrials.gov Identifier: NCT01658826.
authors.affiliation: University of Washington & Fred Hutchinson Cancer Research Center, Seattle.
authors.forename: Anna
authors.initials: A
authors.lastname: Wald
authors.affiliation: AiCuris Anti-infective Cures GmbH, Wuppertal, Germany.
authors.forename: Burkhard
authors.initials: B
authors.lastname: Timmler
authors.affiliation: University of Washington & Fred Hutchinson Cancer Research Center, Seattle.
authors.forename: Amalia
authors.initials: A
authors.lastname: Magaret
authors.affiliation: Westover Heights Clinic, Portland, Oregon.
authors.forename: Terri
authors.initials: T
authors.lastname: Warren
authors.affiliation: University of Texas Health Science Center & Center for Clinical Studies, Houston.
authors.forename: Stephen
authors.initials: S
authors.lastname: Tyring
authors.affiliation: University of Washington & Fred Hutchinson Cancer Research Center, Seattle.
authors.forename: Christine
authors.initials: C
authors.lastname: Johnston
authors.affiliation: Indiana University School of Medicine, Indianapolis.
authors.forename: Kenneth
authors.initials: K
authors.lastname: Fife
authors.affiliation: University of Washington & Fred Hutchinson Cancer Research Center, Seattle.
authors.forename: Stacy
authors.initials: S
authors.lastname: Selke
authors.affiliation: University of Washington & Fred Hutchinson Cancer Research Center, Seattle.
authors.forename: Meei-Li
authors.initials: ML
authors.lastname: Huang
authors.affiliation: AiCuris Anti-infective Cures GmbH, Wuppertal, Germany.
authors.forename: Hans-Peter
authors.initials: HP
authors.lastname: Stobernack
authors.affiliation: AiCuris Anti-infective Cures GmbH, Wuppertal, Germany.
authors.forename: Holger
authors.initials: H
authors.lastname: Zimmermann
authors.affiliation: University of Washington & Fred Hutchinson Cancer Research Center, Seattle.
authors.forename: Lawrence
authors.initials: L
authors.lastname: Corey
authors.affiliation: AiCuris Anti-infective Cures GmbH, Wuppertal, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Birkmann
authors.affiliation: AiCuris Anti-infective Cures GmbH, Wuppertal, Germany.
authors.forename: Helga
authors.initials: H
authors.lastname: Ruebsamen-Schaeff
mesh_terms: D000212:Acyclovir / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000009:adverse effects / Q000627:therapeutic use*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005260:Female; D006558:Herpes Genitalis / Q000188:drug therapy* / Q000821:virology; D018258:Herpesvirus 2, Human; D006801:Humans; D008297:Male; D008875:Middle Aged; D011725:Pyridines / Q000009:adverse effects / Q000627:therapeutic use*; D012008:Recurrence; D013449:Sulfonamides; D013844:Thiazoles / Q000009:adverse effects / Q000627:therapeutic use*; D000077483:Valacyclovir; D014633:Valine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D017201:Virus Shedding / Q000187:drug effects*; D055815:Young Adult
chemical_list: D000998:Antiviral Agents; D011725:Pyridines; D013449:Sulfonamides; D013844:Thiazoles; C453221:pritelivir; D014633:Valine; D000077483:Valacyclovir; D000212:Acyclovir