Patients burdened with genital herpes often desire treatments to reduce the frequency of viral shedding, hoping to reduce the rate of transmission. Several antivirals are currently available to reduce viral shedding, each of which has demonstrated some efficacy, but none of which totally eliminates viral shedding.
Herpes simplex virus type 2 (HSV-2) comprises a substantial share of the causes of genital herpes infection. Although two decades ago HSV-2 was responsible for the vast majority of genital herpes infections, the prominent role of HSV-1 in genital herpes has been increasingly recognized since 2006. Clinically, outbreaks are indistinguishable, although nuances of difference between HSV-1 and HSV-2 do exist (e.g., frequency of outbreaks and severity of outbreaks being modestly less with the former).
Pritelivir (PRT) is the first member of a new class of antiviral agents active against both HSV-1 and HSV-2. The mechanism of action — inhibition of the viral helicase-primase complex — differs from currently available nucleosidase analogues.
Wald et al performed a double-blind, placebo-controlled trial among adults (n = 156) with a clinical history of genital herpes and confirmed HSV-2 seropositivity. Subjects performed daily self-swabbing for HSV PCR testing, as well as reporting on occurrences of HSV outbreaks (which had to be confirmed within 24 hours by clinic personnel).
Over the 28-day duration of the study, study subjects who received daily doses of PRT of 25-400 mg/day experienced a significant reduction in the number of days of viral shedding (43-87% reduction, depending on dose). Clinical outbreaks were also dramatically reduced (87% reduction). PRT was well tolerated, with no serious drug-attributable adverse effects. It is uncertain if and when PRT will find clinical utility because animal trials disclosed skin and hematologic abnormalities, albeit at much larger relative doses than used in humans.
Source: Wald A, et al. N Engl J Med 2014;370:201-210.