EXECUTIVE SUMMARY

The U.S. Preventive Services Task Force has published a final recommendation against using current blood tests to screen for genital herpes in people with no signs or symptoms of infection, including adolescents and adults, as well as pregnant women.

  • Although genital herpes is common — the CDC estimates about one out of every six people ages 14-49 in the United States is infected — testing is not generally helpful for people without symptoms, in part because early identification does not improve a person’s health, as there is no cure for the infection.
  • Because of the inaccuracy of current screening methods, harms of screening include high false-positive rates and potential anxiety and disruption of personal relationships related to diagnosis.

Genital herpes is a common sexually transmitted infection (STI) in the United States for which there is no cure nor effective screening tests. The U.S. Preventive Services Task Force (USPSTF) has just published a final recommendation against using current blood tests to screen for genital herpes in patients with no signs or symptoms of infection, including adolescents and adults, as well as pregnant women.1

While genital herpes is common — the CDC estimates about one out of every six people ages 14-49 in the United States is infected — testing is not generally helpful for people without symptoms, in part because early identification does not improve a person’s health, as there is no cure for the infection, says USPSTF member Ann Kurth, PhD, CNM, MSN, MPH, Dean and Linda Koch Lorimer Professor of Nursing at the Yale University School of Nursing.2

“In addition, because current screening methods are often inaccurate, harms of screening include high false-positive rates and potential anxiety and disruption of personal relationships related to diagnosis,” Kurth noted in a statement accompanying the recommendation.

Genital herpes infection is caused by two subtypes of herpes simplex virus (HSV), HSV-1 and HSV-2. Unlike other infections for which screening is recommended, HSV infection may not demonstrate a long asymptomatic period during which screening, early identification, and treatment may alter its course. Randomized trials have indicated that three antiviral medications provide clinical benefit for genital herpes: acyclovir, valacyclovir, and famciclovir.3-6 Although these medications may provide symptomatic relief from outbreaks, they do not cure HSV infection. These systemic antiviral drugs can partially control the signs and symptoms of genital herpes when used to treat first clinical and recurrent episodes or when used as daily suppressive therapy, but do not eradicate latent virus nor affect the risk, frequency, or severity of recurrences after discontinuing the drug.

To update its 2005 recommendation on screening, the USPSTF reviewed evidence on the accuracy, benefits, and harms of serologic screening for HSV-2 infection in asymptomatic persons, including those who are pregnant, as well as the effectiveness and harms of preventive medications and behavioral counseling interventions to reduce future symptomatic episodes and transmission to others. The panel found that serologic screening for genital herpes is associated with a high rate of false-positive test results and potential psychosocial harms. Evidence from randomized, controlled trials does not establish whether preventive antiviral medication for asymptomatic HSV-2 infection has benefit, the panel concluded.1

“People who are concerned about their personal risk or are experiencing signs and symptoms of genital herpes should talk to their primary care clinician,” says USPSTF member Maureen Phipps, MD, MPH, department chair and Chace-Joukowsky professor of obstetrics and gynecology and assistant dean for teaching and research on women’s health at the Warren Alpert Medical School of Brown University. “This is especially true for women who are pregnant because clinicians can help women who have genital herpes minimize the chance of passing this on to their babies.”

New Drug in Research Focus

In related news, results of a small-scale, Phase II trial indicate a new medication may provide greater virus suppression and reduction in lesions for patients with genital herpes.7 In the study, researchers with the University of Washington and Fred Hutchinson Cancer Research Center compared the medications pritelivir and valacyclovir for reducing genital herpes simplex virus shedding and lesions in persons with recurrent genital herpes.

For the crossover study, 91 participants (adults with four to nine annual genital HSV-2 recurrences) were randomly assigned to two groups: 45 to receive pritelivir first, and 46 to receive valacyclovir first. Participants took the first drug for 28 days, followed by 28 days of washout before taking the second drug for 28 days. Throughout treatment, the participants collected genital swabs four times daily for HSV testing. The FDA placed the trial on clinical hold based on findings in a concurrent nonclinical toxicity study, and the sponsor terminated the study.

Of the 91 randomized participants, 56 had completed both treatment periods at the time of the study’s termination. In intent-to-treat analyses, HSV shedding was detected in 2.4% of swabs during pritelivir treatment, compared with 5.3% during valacyclovir treatment. Genital lesions were present on 1.9% of days in the pritelivir group vs. 3.9% in the valacyclovir group. Researchers note the frequency of shedding episodes did not differ by group. Quantity of virus shed decreased significantly during pritelivir treatment compared with valacyclovir treatment. The frequency of pain was lower in the pritelivir group compared to the valacyclovir group. Treatment-emergent adverse events occurred in 62% of participants in the pritelivir group and 69% of participants in the valacyclovir group.7

Although clinical trials conducted so far in humans have shown no serious side effects, the FDA put a hold on the drug’s clinical use in 2013 because of skin and blood abnormalities shown in a concurrent animal trial. The hold came while the University of Washington study was underway, forcing it to end early.

The German drug maker AiCuris is working with the FDA to partially lift the hold so that pritelivir can be tested in a new clinical trial on patients who are resistant to drugs in the acyclovir family, which includes acyclovir, famciclovir, and valacyclovir.

“I hope that if the trial for acyclovir-resistant HSV goes well, we would be able to go back to the general population with further trials,” said lead author Anna Wald, MD, MPH, University of Washington and Fred Hutchinson Cancer Research Center researcher. “It’s important to develop new drugs for this incredibly common infection.”

REFERENCES

  1. Feltner C, Grodensky C, Ebel C, et al. Serologic screening for genital herpes: An updated evidence report and systematic review for the US Preventive Services Task Force. JAMA 2016;316:2531-2543.
  2. Centers for Disease Control and Prevention. Sexually Transmitted Disease Surveillance, 2014. Atlanta, GA: Department of Health and Human Services; December 2014.
  3. Diaz-Mitoma F, Sibbald RG, Shafran SD, et al. Collaborative Famciclovir Genital Herpes Research Group. Oral famciclovir for the suppression of recurrent genital herpes: A randomized controlled trial. JAMA 1998;280:887-892.
  4. Mertz GJ, Loveless MO, Levin MJ, et al. Collaborative Famciclovir Genital Herpes Research Group. Oral famciclovir for suppression of recurrent genital herpes simplex virus infection in women: A multicenter, double-blind, placebo-controlled trial. Arch Intern Med 1997;157:343-349.
  5. Reitano M, Tyring S, Lang W, et al. International Valaciclovir HSV Study Group. Valaciclovir for the suppression of recurrent genital herpes simplex virus infection: A large-scale dose range-finding study. J Infect Dis 1998;178:603-610.
  6. Romanowski B, Marina RB, Roberts JN; Valtrex HS230017 Study Group. Patients’ preference of valacyclovir once-daily suppressive therapy versus twice-daily episodic therapy for recurrent genital herpes: A randomized study. Sex Transm Dis 2003;30:226-231.
  7. Wald A, Timmler B, Magaret A, et al. Effect of pritelivir compared with valacyclovir on Genital HSV-2 shedding in patients with frequent recurrences: A randomized clinical trial. JAMA 2016;316:2495-2503.