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Home Treatment Options Treatment Options The Treatment Landscape: What's Now, What's Next

The Treatment Landscape: What's Now, What's Next

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In 1981, the New England Journal of Medicine published an article on a research study on the effectiveness of the then-experimental herpes drug acyclovir in bone-marrow-transplant recipients. While the study was small and focused on a specific subset of patients, the news that acyclovir was capable of preventing HSV reactivation caught the attention of several major media outlets. As The Helper reported at the time, most news organizations covered this new development accurately. Others, however, interpreted the results with . . . well, a less than critical eye. The perceived broader implications of the study led one newscaster to proclaim this bit of hyperbole: “The cure for herpes is here.”

Flash forward to today, more than 25 years later. A great deal more research has been done, clinical trials have been completed, and new antiviral treatments have been developed. While you won’t be hearing proclamations of a herpes “cure” (well, aside from spam e-mails, fly-by-night websites or other such less-than-reputable sources), we are today at a point where a number of options are available to effectively treat and manage genital herpes infection. Current antiviral therapies may not be a full-fledged “cure,” but for many they offer significant promise in limiting recurrences, reducing the risk of transmission, and improving quality of life. Pills

We aim here to examine recent research and recommendations on the three FDA-approved antiviral treatments—acyclovir, valacyclovir, and famciclovir—currently available, as well as take a look at future options currently under development, including vaccines and microbicides. Certainly, some may prefer alternative approaches, such as traditional Chinese medicine, homeopathy, or acupuncture, for either financial or philosophical reasons, or perhaps both. Yet while we’ve explored complementary and alternative therapies a number of times in previous issues of The Helper (and see our piece on page 3 for a discussion on exploring and evaluating alternative approaches for managing herpes), our focus here lies with therapies proven effective through well-designed clinical trials. Treatment— according to a recent meta-analysis—that works.

No hyperbole here. This was indeed the news reported in the Journal of the American Academy of Dermatology in August 2007. Researchers in France conducted the first meta-analysis* on the effectiveness of prophylactic oral antiviral treatment (acyclovir, valacyclovir, and famciclovir) to prevent recurrent genital herpes. They examined 14 studies of randomized clinical trials, involving a total of 6158 participants, published over a twenty-year period (1984 to 2004). The analysis led to the conclusion that all three antiviral therapies were highly effective compared with a placebo and reduced the global relative risk of recurrence by nearly 50 percent.

While the researchers acknowledge some limitations in their analysis, their results show that suppressive treatment was effective in not only reducing recurrences, but produced additional benefits as well. While acknowledging some “community level” benefits of suppressive therapy, such as the economic benefit of fewer physician visits and greater workplace productivity (due to fewer recurrences), they also note a reduced transmission risk. Research has demonstrated that suppressive therapy can reduce asymptomatic viral shedding and, in the case of valacyclovir, reduce the risk of transmission to an uninfected partner. In the case of valacyclovir, this particular study, conducted by some of the most noted HSV researchers in the field, demonstrated that daily therapy with valacyclovir could cut the risk of transmission to an uninfected partner in half. The study followed 1,484 heterosexual couples in which one partner was seropositive for genital HSV2 and had a history of recurrences, while the other was uninfected with genital herpes. These participating couples, who were counseled on prevention and condom use, were followed for 8 months. In each case, the HSV-2 positive partner took either a 500mg daily dose of valacyclovir or a placebo. The result—a 50 percent reduced rate of transmission for those treated with valacyclovir.

The valacyclovir study was an important one for a number of reasons. Certainly, it demonstrated that couples can take clear steps to reduce the risk of transmission with daily therapy and safer sex practices. Additionally, though, this study demonstrated that an antiviral drug can be used to effectively prevent transmission of a sexually transmitted infection—opening the door to the possibility that antiviral treatment might be studied as a means to prevent the transmission of other STIs, such as HIV.

Yet while the benefit and effectiveness of suppressive therapy seems evident, daily treatment isn’t necessarily for everyone. It can be expensive, perhaps difficult to manage, and for those with infrequent outbreaks, perhaps unnecessary. For some, treatment of outbreaks as they occur (otherwise known as “episodic” therapy) may be the better option. For those that choose this route, the good news in recent years has been fewer days of treatment, with comparable results.

*A meta-analysis is a statistical practice combining the results from a number of studies that address the same hypotheses, in an attempt to summarize all of the findings relating to a particular issue.

The Long and Short of Episodic Therapy
Until quite recently, the standard for episodic treatment was a 5-day course of medication. A number of studies in recent years have shown, however, that shorter courses of antiviral treatment— as short as one day—are just as effective, in addition to being less expensive and easier to follow.

The International Herpes Management Forum (IHMF), publisher of the journal Herpes, held a workshop in June 2006 to develop practical recommendations for episodic therapies for both genital and oral herpes. They reported on the conclusions of the meeting in the June 2007 issue of Herpes, offering new recommendations for short-course antiviral therapy as the new “standard” of care.

Given new research into ever-shorter treatment regimens to manage outbreaks, workshop participants reviewed and revised existing recommendations. Among the recommendations ratified by workshop participants was the following: “Healing rates for short-course (1-, 2- or 3-day) therapy of oral and labial HSV are equal to those of 5-day courses. These newer, shorter course regimens are both more convenient and economical and can be utilized.” Specific recommendations for treatment include 1-and 2 day treatment with famciclovir (either 1000mg twice daily; and 500mg initially followed by 250mg 12-hourly for 2 days), 3-day treatment with valacyclovir (500mg twice daily) and 2-day treatment with acyclovir (800mg three times daily).

In a nutshell, treatment of outbreaks has become faster and cheaper, while remaining just as effective as before. Short-course, high dose treatment regimens are not only effective, but appear to be safe and well tolerated. But what about that elusive “cure” then? What’s looming ahead in the field of herpes research? One potentially powerful new tool in herpes prevention that isn’t far off—a herpes vaccine.

An Ounce of Prevention
Perhaps one of the most anticipated outcomes in the field of herpes research is the development of a herpes vaccine. Perhaps the most promising vaccine currently in development is the investigational HSV-2 glycoprotein-D– subunit vaccine with alum and 3-Odeacylated-monophosphoryl lipid A, currently in its final phase of clinical trials—the HerpeVac trial for women.

The result of a partnership between the National Institute of Allergy and Infectious Diseases and the vaccine’s manufacturer, GlaxoSmithKline, the HerpeVac clinical trial is recruiting 7,550 women in 40 states to test the effectiveness of the investigational vaccine. In earlier testing among 7,400 men and women, the vaccine was proven to be effective in women who were not previously infected with HSV (1 or 2). In these women, the risk of contracting symptomatic genital herpes was reduced by approximately 75 percent. The risk of developing herpes antibodies was reduced nearly 40 percent.

Promising results to be sure, but within limits. These earlier clinical trials did not show any benefit from vaccination for women who were previously infected with HSV, or in men, regardless of HSV status. Nevertheless, the vaccine was shown to be safe, well tolerated with few side effects reported, and effective in at least one subset of the population— uninfected females.

What about a therapeutic vaccine for those already infected with HSV? To this point, many of the therapeutic vaccines in development have not proven successful in early testing. However, one particular trial (of the gD2-alum vaccine) in 98 individuals with recurrent genital herpes showed promise. In this double-blind, placebo-controlled trial, participants who received the vaccine reported 24% fewer recurrences per month than the control group, and 36% fewer culture-proven recurrences per month. While much more work remains in the development of therapeutic vaccine, the trial did provide a “proof of principle” that such vaccines can impact the history of HSV infection.

As we await the development of a safe and effective vaccine, what else lies ahead in the field of treatment and transmission prevention? One area that is drawing attention—topical microbicides.

The Promise of Microbicides
A number of topical products are currently being studied for effectiveness in preventing both transmission and recurrences of genital herpes. While no topical microbicide has been approved for use in the prevention of genital herpes or other STIs, and early studies have shown limited effectiveness for therapeutic use, the development of a safe and effective product could provide another tool for prevention.

One microbicide, SPL7013 (the active ingredient in VivaGel®, a vaginal microbicide gel) has successfully completed Phase I safety trials and recently commenced enrollment for Phase II clinical trials of young women in San Francisco and Kenya, supported by funding from the National Institutes of Health. While SPL7013 has been studied in the prevention of HIV, it has also demonstrated activity against HSV2 and is being investigated as a means to prevent transmission of genital herpes as well. A safety trial is also underway at the Melbourne Sexual Health Centre in Melbourne, Australia with male participants.

There are of course other experimental microbicides in various stages of development at the moment, including additional agents that have shown activity against HSV. Whether or not microbicides will prove to have any therapeutic effect remains to be seen in future clinical trials. But while promising for the prevention of not just genital herpes but also HIV and other STIs, what of further advances in treatment, or better yet, the elusive cure?

Again, no hyperbole here. However, none is needed to extol the advancements that have been made in treatment and prevention during the last twenty-five years. Far from the days when antivirals were just a concept showing promise in animal studies—a wide range of options for managing genital herpes and stopping the spread of HSV infection is now available. Still, no claims that “the cure is here” . . .yet. But keep your eyes in these pages.

Want to learn more?
For those looking for more in-depth information on recent developments and recommendations in the treatment of genital herpes, check out the following articles and websites:

“Recommendations for Short-course Therapies in Herpes Genitalis and Herpes Labialis” Herpes June 2007; Volume 14, Supplement 1

“A meta-analysis to assess the efficacy of oral antiviral treatment to prevent genital herpes outbreaks.” Lebrun-Vignes, B., et al. Journal of the American Academy of Dermatology 2007; 57(2): 238-246

“Once-daily valaciclovir to reduce the risk of transmission of genital herpes” Corey L, Wald A, Patel R, Sacks SL, Tyring SK, Warren T et al. New England Journal of Medicine 2004; 350:11–20

“Glycoprotein-D-Adjuvant Vaccine to Prevent Genital Herpes.” Stanberry L, et al. New England Journal of Medicine 2002; 347:1652-61

The HerpeVac Clinical Trial for Women

 

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