Is aciclovir (antiviral medication) effective for preexposure prophylaxis (PrEP) for HIV (Human Immunodeficiency Virus) or other sexually transmitted infections (STIs)?

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Last updated: October 10, 2025View editorial policy

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Aciclovir Is Not Recommended for HIV Pre-Exposure Prophylaxis

Aciclovir is not recommended for pre-exposure prophylaxis (PrEP) against HIV or other sexually transmitted infections. The current evidence does not support its use for this purpose, and tenofovir disoproxil fumarate with emtricitabine (TDF/FTC) remains the recommended regimen for HIV PrEP.

Evidence Against Aciclovir for HIV PrEP

  • A randomized, double-blind, placebo-controlled trial specifically evaluated aciclovir for HIV prevention in HSV-2 seropositive individuals and found no reduction in HIV acquisition (hazard ratio 1.16 [95% CI 0.83-1.62]) despite good medication adherence 1.

  • Current guidelines explicitly state that there are no data to indicate that antiherpetic medications (aciclovir, famciclovir, or valacyclovir) can be taken as PrEP to prevent HSV-2 acquisition, let alone HIV acquisition 2.

  • Aciclovir is not mentioned as a potential PrEP agent in any of the HIV prevention guidelines, which focus exclusively on antiretroviral medications 2.

Recommended HIV PrEP Regimens

  • TDF/FTC (tenofovir disoproxil fumarate/emtricitabine) is the recommended PrEP agent for HIV prevention (evidence rating BIII) 2.

  • Daily TDF/FTC is recommended for persons at risk of HIV through sexual exposure (evidence rating AIa) and for people who inject drugs (evidence rating BIa) 2.

  • For men who have sex with men with infrequent sexual exposures, on-demand or event-driven PrEP with TDF/FTC using the "2-1-1" dosing regimen (2 doses 2-24 hours before sex, 1 dose 24 hours after the first dose, and 1 dose 24 hours later) is an effective alternative to daily dosing 2, 3.

Appropriate Uses of Aciclovir

While aciclovir is not recommended for HIV PrEP, it does have established roles in other contexts:

  • Aciclovir is effective for treating and suppressing herpes simplex virus (HSV) infections 2.

  • For patients who have frequent or severe recurrences of genital HSV disease, daily suppressive therapy with oral aciclovir may be indicated (AI) 2.

  • Data are lacking on the effectiveness of acyclovir for preventing chickenpox in susceptible HIV-infected children or adults, although such an approach would be logical (CIII) 2.

Monitoring and Safety Considerations for HIV PrEP

When prescribing appropriate HIV PrEP (TDF/FTC):

  • Regular monitoring is required every 3 months for HIV testing, STI screening, and assessment of renal function 4.

  • TDF-based PrEP is not recommended for persons with creatinine clearance below 60 mL/min/1.73 m² (evidence rating AIIa) 2.

  • Potential side effects of TDF/FTC include gastrointestinal symptoms (14% vs. 5% with placebo) and renal adverse events (18% vs. 10% with placebo) 3.

Common Pitfalls to Avoid

  • Don't confuse HSV and HIV prevention strategies: While aciclovir is effective for HSV treatment and suppression, it does not prevent HIV acquisition 1.

  • Don't assume cross-effectiveness: Medications effective against one virus (like HSV) should not be assumed to work against unrelated viruses (like HIV) without specific evidence.

  • Don't delay appropriate PrEP: Using ineffective agents like aciclovir instead of proven PrEP regimens could leave individuals vulnerable to HIV infection.

  • Don't overlook comprehensive prevention: PrEP should be part of a comprehensive prevention strategy that includes regular HIV/STI testing and condom use 2, 4.

In conclusion, healthcare providers should recommend TDF/FTC-based regimens for HIV PrEP and reserve aciclovir for its approved indications in treating and suppressing herpes virus infections.

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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