What is the recommended diagnostic work‑up and management—including antiviral therapy, suppressive therapy, pregnancy considerations, and options for resistant infection—in an adult presenting with recurrent painful genital vesicles or ulcers suggestive of herpes simplex virus type 2?

Management of Recurrent Genital HSV-2 Infection

For adults with recurrent painful genital vesicles or ulcers suggestive of HSV-2, initiate oral antiviral therapy immediately—either episodic treatment at first symptom onset or daily suppressive therapy if experiencing ≥6 recurrences per year—and counsel patients about transmission risk, natural history, and pregnancy implications. 1

Diagnostic Work-Up

Laboratory Confirmation

• Obtain PCR from active genital lesions as the preferred diagnostic method due to its superior sensitivity, especially for suboptimal specimens or non-vesicular presentations 2
• Perform viral typing on all positive specimens to distinguish HSV-1 from HSV-2, as this fundamentally changes prognosis and counseling—genital HSV-1 recurs in only 55% of patients at 12 months versus 90% for HSV-2 2
• Consider type-specific serologic testing (glycoprotein G-based assays) to diagnose unrecognized infections or confirm HSV-2 status in patients with atypical presentations 2
• Do not delay treatment awaiting laboratory results—initiate antiviral therapy based on clinical presentation alone 1

Clinical Assessment

• Examine for characteristic grouped vesicles on an erythematous base, painful shallow ulcers, or crusted lesions in the genital, perigenital, or anal regions 3
• Ask specifically about prodromal symptoms (tingling, burning, itching) that precede lesion appearance, as this guides episodic therapy timing 1
• Document recurrence frequency over the past year to determine candidacy for suppressive therapy 1

Antiviral Therapy

Episodic Treatment for Recurrent Episodes

• Prescribe one of three equivalent regimens for 5 days:
  • Valacyclovir 1 g orally twice daily, OR
  • Acyclovir 400 mg orally three times daily, OR
  • Famciclovir 250 mg orally three times daily 1
• Provide patients with a prescription or medication supply for self-initiation at the first prodromal sign or within 24 hours of lesion appearance to achieve maximal benefit 1
• Initiate treatment as early as possible, ideally within 72 hours, though clinical benefit may still occur with later initiation 1

Daily Suppressive Therapy

Offer suppressive therapy to patients with ≥6 recurrences per year or those experiencing significant psychological distress from genital HSV. 1

• Recommended suppressive regimens (choose one):
  • Valacyclovir 500 mg once daily (most convenient option), OR
  • Valacyclovir 1000 mg once daily, OR
  • Acyclovir 400 mg twice daily, OR
  • Famciclovir 250 mg twice daily 1
• Use valacyclovir 1000 mg daily or alternative agents for patients with ≥10 recurrences per year, as 500 mg once daily may be insufficient 1
• Suppressive therapy reduces recurrence frequency by ≥75% and has documented safety for continuous use up to 6 years with acyclovir and up to 1 year with valacyclovir or famciclovir 1
• For HIV-infected patients, use valacyclovir 500 mg twice daily (not once daily) or twice-daily regimens with acyclovir or famciclovir 4

Adjunctive Symptomatic Care

• Recommend oral analgesics (acetaminophen or NSAIDs) for pain relief 1
• Suggest sitz baths or topical ice application to reduce discomfort 1
• Avoid topical antivirals—they are substantially less effective than systemic oral therapy 1

Management of Resistant Infection

Acyclovir-Resistant HSV

• Acyclovir resistance is not a cause of clinical failure in immunocompetent patients and occurs almost exclusively in immunocompromised individuals 1
• For confirmed acyclovir-resistant HSV (primarily in HIV-infected patients), administer IV foscarnet as the treatment of choice 4
• Consider topical trifluridine, cidofovir, or imiquimod for external lesions in resistant cases, though prolonged application for 21–28 days or longer may be required 4
• Perform susceptibility testing to confirm drug resistance before switching to alternative agents 4

Pregnancy Considerations

Antiviral Management During Pregnancy

• Acyclovir is the first-choice antiviral for HSV infections in pregnancy due to the most extensive safety data 4
• Offer episodic therapy for first-episode HSV disease and recurrences during pregnancy, but suppressive therapy is not used routinely except in late pregnancy 4
• Initiate suppressive-dose acyclovir 400 mg three times daily starting at week 36 of gestation to prevent HSV recurrences requiring cesarean delivery at term 4, 5

Delivery Management

• Recommend cesarean delivery for women with genital herpes prodrome or visible HSV genital lesions at the onset of labor to prevent neonatal transmission 4
• The risk of neonatal HSV transmission is highest when maternal acquisition occurs in late pregnancy (third trimester), with rates substantially lower in women with recurrent infection 6
• Counsel uninfected pregnant women to avoid sexual contact during the third trimester if their partner has genital herpes 6

Counseling for Women of Childbearing Age

• Women of childbearing age should inform their obstetric providers of genital HSV infection in any pregnancy because of neonatal transmission risk 1

Patient Counseling

Natural History and Transmission

• Most individuals with first-episode genital HSV-2 infection will experience subsequent recurrences, which tend to be milder and more localized 1
• Recurrence frequency generally declines over time, and asymptomatic viral shedding is most common during the first 12 months after infection 1
• Approximately 60% of individuals exposed to HSV-2 do not develop symptoms, yet can still transmit the virus through asymptomatic shedding 5
• Counsel patients about asymptomatic shedding and transmission risk, emphasizing that transmission can occur even without visible lesions 4

Prevention Strategies

• Discuss suppressive antiviral therapy as a method to reduce transmission to serodiscordant partners 5
• Recommend abstaining from sexual activity during prodromal symptoms or when lesions are present 4
• Advise consistent condom use, which reduces HSV transmission risk by approximately 70% when used correctly 5
• Encourage disclosure to sexual partners as part of comprehensive prevention counseling 4

HSV-1 vs. HSV-2 Counseling Differences

• Genital HSV-1 is associated with markedly lower viral shedding and fewer recurrences than HSV-2, especially after the first year of infection 1
• Transmission to sexual partners is less likely with genital HSV-1 due to reduced shedding frequency 1
• Episodic antiviral therapy is the recommended approach for genital HSV-1 recurrences; daily suppressive therapy has not demonstrated reduction in transmission risk and its risk-benefit profile is uncertain 1, 5

Severe Disease Requiring Hospitalization

• Administer intravenous acyclovir 5–10 mg/kg every 8 hours for 5–7 days (or until clinical resolution) in cases of disseminated infection, pneumonitis, hepatitis, or CNS involvement (meningitis, encephalitis) 1

Common Pitfalls to Avoid

• Do not rely on topical antivirals—they are substantially less effective than systemic oral therapy 1
• Do not delay treatment awaiting laboratory confirmation—initiate antiviral therapy based on clinical presentation 1
• Do not assume treatment failure in immunocompetent patients is due to acyclovir resistance—this occurs almost exclusively in immunocompromised individuals 1
• Do not use valacyclovir 500 mg once daily for HIV-infected patients—use 500 mg twice daily instead 4
• Do not recommend routine serologic screening in asymptomatic individuals with low pretest probability—it is not indicated 5