JAMA: In a study appearing in the December 20 issue of JAMA, Anna Wald, M.D., M.P.H., of the University of Washington & Fred Hutchinson Cancer Research Center, Seattle, and colleagues compared the medications pritelivir and valacyclovir for reducing genital herpes simplex virus shedding and lesions in persons with recurrent genital herpes. The treatment for genital herpes simplex virus (HSV) infections relies on the nucleoside analogues acyclovir, valacyclovir, or famciclovir administered either for each recurrence or daily to prevent recurrences. In addition, valacyclovir, when taken daily has been shown to reduce the risk of HSV-2 transmission to susceptible partners. However, the protection is only partial (approximately 50 percent), likely because these drugs neither completely inhibit genital viral shedding (when the virus is active and potentially transmissible to sexual partners). Alternative agents to treat HSV infections are needed.
For this crossover study, 91 participants (adults with 4 to 9 annual
genital HSV-2 recurrences) were randomly assigned, 45 to receive
pritelivir first, a different class of medication for genital herpes,
and 46 to receive valacyclovir first. 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 HSV testing. The U.S. Food and Drug
Administration placed the trial on clinical hold based on findings in a
concurrent nonclinical toxicity study, and the sponsor terminated the
Of the 91 randomized participants, 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 percent of swabs during
pritelivir treatment compared with 5.3 percent during valacyclovir
treatment. Genital lesions were present on 1.9 percent of days in the
pritelivir group vs 3.9 percent in the valacyclovir group. The frequency
of shedding episodes did not differ by group. Quantity of virus shed
was decreased significantly during pritelivir treatment compared with
valacyclovir treatment. The frequency of pain was reduced in the
pritelivir group compared to the valacyclovir group.
Treatment-emergent adverse events occurred in 62 percent of
participants in the pritelivir group and 69 percent of participants in
the valacyclovir group.
“Further research is needed to assess longer-term efficacy and safety,” the authors write.
(doi:10.1001/jama.2016.18189; the study is available pre-embargo at the For the Media website)