Breakthrough herpes episodes occur even with high-dose antivirals

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Shedding Persists in Herpes Even With High-Dose Antivirals
Shedding Persists in Herpes Even With High-Dose Antivirals

HealthDay News -- Patients with herpes simplex virus type 2 (HSV-2) taking high doses of antiviral therapy to control the disease continue to experience short episodes of subclinical shedding or reactivation, researchers reported online in Lancet.

The findings help explain why even high-doses of antiherpetic drugs do not prevent HSV transmission, according to Christine Johnston, MD, of the University of Washington in Seattle, and colleagues.

They conducted three randomized open-label cross-over studies involving 113 patients, that compared no medication with the following herpes treatment regimens:

  • Standard-dose 400 mg acyclovir (Zovirax) twice daily
  • Standard-dose 500 mg valacyclovir (Valtrex) daily with high-dose 800 mg acyclovir three times daily
  • Standard-dose valacyclovir with high-dose 1 g valacyclovir three times daily

Participants were assigned to a treatment arm for four to seven weeks and had one week of wash-out without treatment before being switched over to the other arm. Participants collected genital swabs four times daily for quantitative HSV DNA polymerase chain reaction (PCR). Ninety patients were eligible for analysis of the primary endpoint

Overall, 5.4% percent of the 23,605 collected swabs were HSV-positive, data indicated. Among the 2,123 swabs obtained by 23 participants who were not receiving treatment the virus was found in 384 (or 18%) of them.

The frequency of viral shedding varied by therapy type, with patients in the standard-dose aciclovir group experienced significantly less HSV shedding than those in the no-medication group (1.2% vs. 18.1%), whereas patients taking high-dose valacyclovir experienced slightly less shedding than those on standard-dose valacyclovir (3.3% vs. 5.8%), and similar shedding rates among patients taking high-dose acyclovir and standard dose valacyclovir (4.2% vs. 4.5%).

Although high-dose valcyclovir reduced HSV shedding 50%, the rate of breakthrough shedding episodes did not change among groups.

The number of such episodes per person year ranged from a high of 28.7 for no medication to a low of 10 for standard-dose acyclovir, while in the other four treatment groups the rates ranged from 14.9 to 22.6.

The number of episodes per person-year did not differ significantly for standard-dose valacyclovir versus high-dose acyclovir (22.6 versus 20.2, P=0.54), and standard-dose valacyclovir versus high-dose valacyclovir (14.9 vs. 16.5; P=0.34), but did for no medication and standard-dose aciclovir (28.7 vs. 10, P=0.001)

Median episode duration was significantly longer for no medication compared with standard-dose acyclovir (13 hours vs. seven hours) and for standard-dose valacyclovir compared with high-dose valacyclovir (10 hours vs. seven hours), but did not differ between standard-dose valacyclovir and high-dose acyclovir (eight hours for both).

"That we could not eliminate or even alter the frequency of shedding episodes with high-dose valacylovir suggests that the maximum benefit of shedding reduction has probably been reached for currently available antiviral drugs," the researchers wrote.

In an accompanying editorial Philippe Van de Perre, MD, PhD, and Nicolas Nagot, MD, both of Université Montpellier in Montpellier, France, wrote that new classes of drugs, such as helicase-primase inhibitors, could help, but they would need good long-term coverage and adherence to prevent HSV-2 transmission.

"These needs are unlikely to be met because about 20% of the general population is infected with HSV-2 in the U.S. and Europe, most of whom have no clinical need for antiherpetic therapy," Van de Perre and Nagot wrote.

Other potential HSV control tools, such as vaccines, lack adequate animal models and commitment from pharmaceutical companies and the public sector to support their development, they added.

Several of the study researchers disclosed financial ties to pharmaceutical companies and companies developing HSV vaccines. GlaxoSmithKline provided free drugs for this trial.

Johnston C et al. Lancet. 2012; doi:10.1016/S0140-6736(11)61750-9.

Van de Perre P, Nagot N. Lancet. 2012; doi:10.1016/S0140-6736(11)61614-0.

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