STD Quarterly: Herpes numbers rise — you must know your options
It’s back to the research drawing board in the search for more treatment options for genital herpes. A clinical trial of an experimental drug, resiquimod, has been suspended since preliminary data showed it was not as effective as expected.
Clinicians need more tools to fight the swell of genital herpes infections. According to the Atlanta-based Centers for Disease Control and Prevention (CDC), 45 million Americans ages 12 and older, or one out of five of the total adolescent and adult population, are infected with the herpes simplex virus-2 (HSV-2).1 Since the late 1970s, the number of Americans with genital herpes infection has increased 30%, with the largest increase occurring in young white teens. HSV-2 infection is now five times more common in 12- to 19-year-old whites, and it is twice as common in young adults ages 20-29 than it was 20 years ago, says the CDC.1
The two companies involved in the research of resiquimod, Eli Lilly & Co. of Indianapolis and 3M Pharmaceuticals of St. Paul, MN, are evaluating the recent Phase III trials results and the more positive results seen in earlier Phase II trials to determine whether to conduct additional clinical trials of resiquimod for the treatment of genital herpes, says Terra Fox, Eli Lilly spokeswoman. It is premature to comment on the timing of determining whether the companies will pursue further research of the drug as a potential treatment for the sexually transmitted disease (STD), says Fox.
Initial research of the drug, part of a new class of drugs known as immune response modifiers, had been promising. Results of a pilot study indicated that application of resiquimod to genital herpes lesions appeared to reduce the frequency of recurrences.2 In that study, 52 patients were randomized to receive the drug in one of four dosing regimens. Patients, whose ages ranged from 18 to 60, had a history of recurrent genital herpes, with an average of 10 episodes per year. Patients applied the drug within 24 hours of the onset of symptoms for three weeks and were observed for six months after treatment. The median time to recurrence was 57 days for patients treated with vehicle alone vs. 169 days for those who received the drug. Patients who received placebo had a median of 5.5 recurrences during the six-month observation period, compared with one recurrence among those who received resiquimod.3
In the study, scientists noted that the delay to develop the next herpes lesion recurrence continued long after applications of the topical gel ended, which suggested that the treatment is similar to a vaccination, prompting levels of interferon a, interleukin 12, and other cytokines that boost cell-mediated immunity.
Three options available
Herpes is not curable, but it can be managed with antiviral medications that are used in episodic therapy, which speeds healing when outbreaks occur, or suppressive therapy, where drugs are taken as a preventive measure to reduce the number and severity of outbreaks. Three drugs are available for herpes treatment: acyclovir (Zovirax, GlaxoSmithKline, Research Triangle Park, NC), famciclovir (Famvir, Novartis Pharmaceuticals, East Hanover, NJ), and valacyclovir (Valtrex, GlaxoSmithKline).
According to the CDC, clinicians can choose from one of the following regimens for treatment of the first clinical episode of herpes:
- acyclovir 400 mg orally three times a day for seven to 10 days, or acyclovir 200 mg orally five times a day for seven to 10 days;
- famciclovir 250 mg orally three times a day for seven to 10 days;
- valacyclovir 1 g orally twice a day for seven to 10 days.
For episodic treatment of recurrent genital herpes, the CDC recommends clinicians choose one of the following approaches:
- acyclovir 400 mg orally three times a day for five days, or acyclovir 200 mg orally five times a day for five days, or acyclovir 800 mg orally twice a day for five days;
- famciclovir 125 mg orally twice a day for five days;
- valacyclovir 500 mg orally twice a day for three to five days, or valacyclovir 1 g orally once a day for five days.
For suppressive therapy of recurrent genital herpes, choose from one of the following treatment regimens, advises the CDC:
- acyclovir 400 mg orally twice a day;
- famciclovir 250 mg orally twice a day;
- valacyclovir 500 mg orally once a day, or valacyclovir 1 g orally once a day.4
Reduce HSV transmission
Results of a randomized, double-blind, placebo-controlled trial of valacyclovir, which enrolled 1,494 monogamous, heterosexual couples in which one partner had serologically documented infection with HSV-2 and the other was HSV-2-seronegative, suggest that the drug reduces the likelihood of sexual transmission to the uninfected partner.5
Since suppressive therapy does not entirely prevent clinical recurrences of genital herpes or subclinical viral shedding, patients who use this drug regimen for HSV transmission also should be counseled on consistent use of condoms and abstinence during symptom flare-ups.
Researchers are beginning a new clinical study to examine the use of Famvir in daily treatment vs. treatment only at the time of outbreaks. This study may help providers optimize their management of genital herpes.
"Our goal as physicians is to help patients feel better and to reinforce the need to practice safer sex," states Jennifer Berman, MD, co-director of the Female Sexual Medicine Center at the University of California, Los Angeles. "For those already infected, the study will provide guidance on how better manage patients with genital herpes."
References
1. Centers for Disease Control and Prevention. Genital Herpes. Atlanta: June 2001. Accessed at www.cdc.gov/nchstp/dstd/Fact_Sheets/facts_Genital_Herpes.htm.
2. Spruance SL, Tyring SK, Smith MH, et al. Application of a topical immune response modifier, resiquimod gel, to modify the recurrence rate of recurrent genital herpes: A pilot study. Infect Dis 2001; 184:196-200.
3. Stephenson J. New therapy promising for genital herpes. JAMA 2001; 285:2,182-2,183.
4. Centers for Disease Control and Prevention. Sexually transmitted diseases treatment guidelines 2002. MMWR 2002; 51(RR-6). Accessed at www.cdc.gov/mmwr/PDF/rr/rr5106.pdf.
5. Corey L, Tyring S, Beutner K, et al. Once-daily valaciclovir reduces transmission of genital herpes. Presented at the 42nd Annual Interscience Conference on Antimicrobial Agents and Chemotherapy. San Diego; September 2002.
Its back to the research drawing board in the search for more treatment options for genital herpes. A clinical trial of an experimental drug, resiquimod, has been suspended since preliminary data showed it was not as effective as expected.You have reached your article limit for the month. Subscribe now to access this article plus other member-only content.
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