Genital herpes can reactivate despite high-dose antiviral therapy

A study of antiviral therapy to treat herpes simplex virus type 2 (HSV-2) demonstrated that the virus can reactivate in “breakthrough episodes” even when doses of antiviral therapy are high.

The study, published last month in The Lancet, combined three trials:

• In Trial 1, participants were randomized to standard-dose aciclovir (Zovirax, Zovir, etc.) (400 mg twice daily) or no medication for 4 weeks, followed by a 1-week wash-out period and crossover to the opposite group for another 4 weeks.
• In Trial 2, participants were randomized to standard-dose valaciclovir (Valtrex) (500 mg daily) or high-dose aciclovir (800 mg three times daily) for 7 weeks, followed by a 1-week wash-out period and crossover to the opposite group for 7 additional weeks.
• In Trial 3, subjects were randomized to standard-dose valaciclovir or high-dose valaciclovir (1 g three times daily) for 5 weeks, followed by a 1-week wash-out period and crossover to the opposite group for 5 additional weeks.¹

All three trials demonstrated that short episodes of subclinical shedding persist with both standard-dose and high-dose aciclovir and valaciclovir. Although shedding of HSV-2 decreased 50% in participants who took the highest dose of valaciclovir, compared with standard-dose valaciclovir, the rate of breakthrough shedding did not change—about 16 to 20 episodes every year.

“Despite the increased use of antiviral therapy in the past two decades,” the authors observe, “the prevalence of, and complications from, HSV-2 infection have changed little.”

“Daily antiviral therapy,” they go on to say, “reduces genital lesions and suppresses detection of HSV on genital mucosal surfaces (shedding),” but daily valaciclovir reduces the risk of sexual transmission by only 48%. Furthermore, aciclovir does not reduce the risk of HIV transmission or acquisition, which is heightened in people who have HSV-2.

“The discrepancy between potent suppression of clinical symptoms and failure of antiviral agents to fully prevent HSV transmission is not well understood. Intensive genital secretion collection shows that HSV shedding episodes are three times more frequent than was previously realized.”

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A study of antiviral therapy to treat herpes simplex virus type 2 (HSV-2) demonstrated that the virus can reactivate in “breakthrough episodes” even when doses of antiviral therapy are high.

The study, published last month in The Lancet, combined three trials:

• In Trial 1, participants were randomized to standard-dose aciclovir (Zovirax, Zovir, etc.) (400 mg twice daily) or no medication for 4 weeks, followed by a 1-week wash-out period and crossover to the opposite group for another 4 weeks.
• In Trial 2, participants were randomized to standard-dose valaciclovir (Valtrex) (500 mg daily) or high-dose aciclovir (800 mg three times daily) for 7 weeks, followed by a 1-week wash-out period and crossover to the opposite group for 7 additional weeks.
• In Trial 3, subjects were randomized to standard-dose valaciclovir or high-dose valaciclovir (1 g three times daily) for 5 weeks, followed by a 1-week wash-out period and crossover to the opposite group for 5 additional weeks.¹

All three trials demonstrated that short episodes of subclinical shedding persist with both standard-dose and high-dose aciclovir and valaciclovir. Although shedding of HSV-2 decreased 50% in participants who took the highest dose of valaciclovir, compared with standard-dose valaciclovir, the rate of breakthrough shedding did not change—about 16 to 20 episodes every year.

“Despite the increased use of antiviral therapy in the past two decades,” the authors observe, “the prevalence of, and complications from, HSV-2 infection have changed little.”

“Daily antiviral therapy,” they go on to say, “reduces genital lesions and suppresses detection of HSV on genital mucosal surfaces (shedding),” but daily valaciclovir reduces the risk of sexual transmission by only 48%. Furthermore, aciclovir does not reduce the risk of HIV transmission or acquisition, which is heightened in people who have HSV-2.

“The discrepancy between potent suppression of clinical symptoms and failure of antiviral agents to fully prevent HSV transmission is not well understood. Intensive genital secretion collection shows that HSV shedding episodes are three times more frequent than was previously realized.”

We want to hear from you! Tell us what you think.

A study of antiviral therapy to treat herpes simplex virus type 2 (HSV-2) demonstrated that the virus can reactivate in “breakthrough episodes” even when doses of antiviral therapy are high.

The study, published last month in The Lancet, combined three trials:

• In Trial 1, participants were randomized to standard-dose aciclovir (Zovirax, Zovir, etc.) (400 mg twice daily) or no medication for 4 weeks, followed by a 1-week wash-out period and crossover to the opposite group for another 4 weeks.
• In Trial 2, participants were randomized to standard-dose valaciclovir (Valtrex) (500 mg daily) or high-dose aciclovir (800 mg three times daily) for 7 weeks, followed by a 1-week wash-out period and crossover to the opposite group for 7 additional weeks.
• In Trial 3, subjects were randomized to standard-dose valaciclovir or high-dose valaciclovir (1 g three times daily) for 5 weeks, followed by a 1-week wash-out period and crossover to the opposite group for 5 additional weeks.¹

All three trials demonstrated that short episodes of subclinical shedding persist with both standard-dose and high-dose aciclovir and valaciclovir. Although shedding of HSV-2 decreased 50% in participants who took the highest dose of valaciclovir, compared with standard-dose valaciclovir, the rate of breakthrough shedding did not change—about 16 to 20 episodes every year.

“Despite the increased use of antiviral therapy in the past two decades,” the authors observe, “the prevalence of, and complications from, HSV-2 infection have changed little.”

“Daily antiviral therapy,” they go on to say, “reduces genital lesions and suppresses detection of HSV on genital mucosal surfaces (shedding),” but daily valaciclovir reduces the risk of sexual transmission by only 48%. Furthermore, aciclovir does not reduce the risk of HIV transmission or acquisition, which is heightened in people who have HSV-2.

“The discrepancy between potent suppression of clinical symptoms and failure of antiviral agents to fully prevent HSV transmission is not well understood. Intensive genital secretion collection shows that HSV shedding episodes are three times more frequent than was previously realized.”

We want to hear from you! Tell us what you think.