All three FDA-approved antivirals for HSV-2 work well. Valacyclovir is the most commonly prescribed because it requires fewer daily doses. Acyclovir is the oldest and often cheapest. Famciclovir is a solid alternative if the others cause issues. None eliminate HSV-2 from your body, but all dramatically reduce outbreaks and transmission risk.
Full comparison table
| Drug | Suppressive dose | Episodic dose | Doses/day (suppressive) | Est. monthly cost (generic) | Main advantage |
|---|---|---|---|---|---|
| Valacyclovir | 500mg or 1g once daily | 1g twice daily x5 days | 1 | $15-30 | Once-daily dosing, high bioavailability |
| Acyclovir | 400mg twice daily | 400mg 3x daily x5 days | 2 | $10-20 | Oldest, most studied, often cheapest |
| Famciclovir | 250mg twice daily | 1g twice daily x1 day | 2 | $20-40 | Single-day episodic treatment option |
How do they all work?
All three drugs target the same thing: an enzyme called thymidine kinase that the herpes virus needs to replicate its DNA. When you take these medications, the drug gets converted inside virus-infected cells into a compound that jams this enzyme. The virus can't copy itself, the outbreak stops or never fully develops, and your immune system clears up the mess.
Valacyclovir is a "prodrug" of acyclovir, meaning your body converts it into acyclovir after you swallow it. The advantage is that oral valacyclovir achieves about 3-5x higher blood levels of active acyclovir than taking acyclovir directly. This is why you can take valacyclovir just once a day rather than twice.
Famciclovir works the same way but gets converted to penciclovir instead. It stays active in infected cells longer, which is why there's a single-day episodic treatment option.
Which should you ask for?
If you want the simplest regimen with once-daily dosing, valacyclovir is the usual first choice. The majority of people who take it report no side effects at all.
If cost is the primary concern, acyclovir is often the cheapest option. The twice-daily suppressive dosing is easy to build into a routine.
Famciclovir is a good alternative if someone doesn't tolerate valacyclovir or acyclovir for some reason. It's also useful if you want a single-day episodic option rather than taking pills for five days.
Bottom line: any of these three is a reasonable starting point. If the first one you try has side effects or doesn't feel like a good fit, you can switch. They're all well-tolerated and have decades of safety data.
Side effects: what to actually expect
The side effect profiles for all three drugs are quite mild. The most common issues, when they happen at all, are headache and mild nausea, especially in the first few days as your body adjusts.
Serious side effects are rare but exist. At high doses (much higher than what's used for HSV-2), valacyclovir and acyclovir can potentially affect kidney function. This is not a concern at standard suppressive doses for healthy adults, but if you have kidney disease, your doctor will adjust the dose accordingly.
These medications have been used for decades and have excellent safety records. Many people take suppressive therapy for years without issues.
Valacyclovir
The most popular choice. Once-daily dosing, excellent effectiveness, well-studied. Generic is affordable.
Full guide →Acyclovir
The original. In use since 1982, extremely well-studied, often the cheapest option.
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Frequently asked questions
Which antiviral is best for HSV-2?
Valacyclovir is most commonly prescribed because it requires fewer daily doses while achieving similar effectiveness. All three approved antivirals work well; the best choice depends on your dosing preferences and cost considerations. Your doctor can help make that call.
How much do HSV-2 antivirals cost?
Generic valacyclovir runs about $15-30/month for suppressive therapy. Generic acyclovir is often slightly cheaper. With GoodRx or similar discount programs, costs can be reduced further. Brand-name versions cost significantly more but offer no benefit over generics.
Can I take antivirals long-term?
Yes. People take suppressive antiviral therapy for HSV-2 for years or even decades with good safety profiles. Long-term studies show no significant safety concerns at standard doses. Some people choose to take a break after several years to see if outbreaks have naturally reduced.
Related: Treatment overview | Valacyclovir guide | Acyclovir guide