Shedding Persists in Herpes Even With High-Dose Antivirals

Reactivation likely accounts for transmission during therapy; new treatments needed

THURSDAY, Jan. 5 (HealthDay News) -- Short episodes of subclinical shedding or reactivation persist in herpes simplex virus type 2 (HSV-2) infection, even in patients on high doses of antiviral therapy, according to a study published online Jan. 5 in The Lancet.

Christine Johnston, M.D., of the University of Washington in Seattle, and colleagues conducted three randomized, open-label, cross-over studies. They compared no medication with standard-dose acyclovir (400 mg twice daily), standard-dose valacyclovir (500 mg daily) with high-dose acyclovir (800 mg three times daily), and standard-dose valacyclovir with high-dose valacyclovir (1 g three times daily). Study periods lasted four to seven weeks, separated by one week of wash-out. A total of 113 participants (with 90 eligible for analysis of the primary end point) collected genital swabs four times daily for quantitative HSV DNA polymerase chain reaction.

The researchers found that 5.4 percent of the 23,605 collected swabs were HSV-positive. The frequency of HSV shedding was significantly less in the standard-dose acyclovir group than in the no-medication group (1.2 versus 18.1 percent). High-dose acyclovir was associated with somewhat less shedding than standard-dose valacyclovir (4.2 versus 4.5 percent), and high-dose valacyclovir was associated with less shedding than standard-dose valacyclovir (3.3 versus 5.8 percent). Although HSV shedding was reduced by 50 percent with the high-dose valacyclovir, the rate of breakthrough shedding episodes did not change. Median episode duration was significantly longer for no medication compared with standard-dose acyclovir (13 versus seven hours) and for standard-dose valacyclovir compared with high-dose valacyclovir (10 versus seven hours), but did not differ between standard-dose valacyclovir and high-dose acyclovir (eight hours for both).

"Short bursts of subclinical genital HSV reactivation are frequent, even during high-dose antiherpes therapy, and probably account for continued transmission of HSV during suppressive antiviral therapy. More potent antiviral therapy is needed to eliminate HSV transmission," write the authors.

Several authors disclosed financial ties to pharmaceutical companies and companies developing HSV vaccines. GlaxoSmithKline provided free drugs for this trial.

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