Is pre-exposure prophylaxis (PrEP) with antiviral medications, such as valacyclovir (valacyclovir hydrochloride) or acyclovir, effective for primary prevention against herpes?

Pre-exposure Prophylaxis Against Herpes Simplex Virus

Pre-exposure prophylaxis (PrEP) with antiviral medications such as valacyclovir or acyclovir is not recommended for primary prevention of herpes simplex virus (HSV) acquisition. 1

Evidence Against HSV PrEP

• There are no data to indicate that antiherpesvirus medications (acyclovir, famciclovir, or valacyclovir) can be taken as PrEP to prevent HSV-2 acquisition 1
• The CDC explicitly states that prophylaxis of initial episodes of HSV disease is not recommended 1
• Current guidelines from infectious disease societies do not support the use of antiviral medications for primary prevention in individuals without HSV infection 1

Alternative Prevention Strategies

• Consistent and correct use of latex condoms during every act of sexual intercourse is recommended to reduce the risk of exposure to HSV and other sexually transmitted infections 1
• Avoiding sexual contact when herpetic lesions (genital or orolabial) are evident is strongly advised 1
• Being aware that asymptomatic viral shedding can occur and lead to transmission even in the absence of visible lesions 1

Special Considerations for HIV PrEP and HSV Prevention

• Among HIV/HSV-2-seronegative individuals in heterosexual discordant partnerships, daily tenofovir disoproxil fumarate (TDF) was associated with a 30% reduced risk of HSV-2 seroconversion 1
• Daily TDF/emtricitabine (FTC) was not associated with decreased risk of HSV-2 acquisition among men who have sex with men and transgender women, but showed lower risk of moderate to severe genital ulcers 1
• On-demand PrEP with TDF/FTC did not show decreased risk for HSV-2 acquisition 1
• While oral TDF/FTC when used for HIV prevention may decrease the risk of HSV-2 acquisition in heterosexual populations, there is insufficient evidence to recommend it solely for HSV prevention 1

Prevention of HSV Transmission in Discordant Couples

• For individuals already infected with HSV-2 who wish to prevent transmission to uninfected partners, suppressive therapy with valacyclovir 500 mg daily has been shown to reduce the risk of transmission 2
• Valacyclovir demonstrated a 75% reduction in symptomatic HSV-2 acquisition and a 48% reduction in overall HSV-2 acquisition in susceptible partners of infected individuals 2
• Both partners should be counseled on safer sex practices and advised to use condoms throughout any sexual activity 2

Suppressive Therapy for Recurrent HSV Infections

• Daily suppressive therapy is indicated for individuals with frequent recurrences (six or more per year) but not for primary prevention 1
• Recommended regimens for daily suppressive therapy include:
  • Acyclovir 400 mg orally twice a day 1
  • Famciclovir 250 mg orally twice a day 1
  • Valacyclovir 250 mg orally twice a day, 500 mg once daily, or 1,000 mg once daily 1
• Valacyclovir appears to be somewhat better than famciclovir for suppression of genital herpes and associated viral shedding 3

Common Pitfalls and Caveats

• Despite the ability of suppressive therapy to reduce viral shedding, it does not completely eliminate asymptomatic viral shedding, so transmission risk remains 1
• Patients should be informed that even with suppressive therapy and condom use, there is still a risk of HSV transmission 2
• Valacyclovir 500 mg twice daily has not been shown to prevent recurrent HSV-2 meningitis and is not recommended for this purpose 1, 4
• The safety of systemic acyclovir and valacyclovir therapy in pregnant women has not been fully established, though current registry findings do not indicate an increased risk for major birth defects 1

In conclusion, while antiviral medications are effective for treating active HSV infections and preventing recurrences in infected individuals, they are not recommended for primary prevention (PrEP) in uninfected individuals.