A nucleoside analog antiviral that is the prototype agent for herpes virus infections. Active against herpes simplex virus types 1 and 2 (HSV-1, HSV-2) and varicella-zoster virus (VZV). Used for genital herpes (initial and recurrent episodes, chronic suppression), herpes zoster (shingles), varicella (chickenpox), herpes encephalitis (IV), and neonatal herpes (IV). Requires conversion to the active form by viral thymidine kinase, providing selective toxicity.
Evidence rating strong. Most-documented uses: treats primary and recurrent genital herpes (hsv-1, hsv-2), chronic suppressive therapy for recurrent genital herpes, treats herpes zoster (shingles). 10 sources indexed (1987–2025), with 5 interaction records on file.
The science
How it works, mechanistically.
Core mechanism
A prodrug (acyclic guanosine analog) that requires three phosphorylation steps for activation. Viral thymidine kinase (encoded by HSV/VZV) performs the first phosphorylation to acyclovir monophosphate, this step is ~3000x more efficient in virus-infected cells, providing selectivity. Cellular kinases then convert it to the active triphosphate form. Acyclovir triphosphate competitively inhibits viral DNA polymerase and, once incorporated into the growing DNA chain, acts as a chain terminator because it lacks the 3'-hydroxyl group needed for subsequent nucleotide addition.
Class
Nucleoside Analog Antiviral
Dosing
Dosing & protocol.
Common range
Genital herpes initial: 400 mg TID or 200 mg 5x/day x 7-10 days; suppressive: 400 mg BID; herpes zoster: 800 mg 5x/day x 7-10 days; IV encephalitis: 10 mg/kg every 8 hours x 14-21 days (as prescribed by your physician)
Recommended form
Oral capsules, tablets, suspension; IV for severe/CNS infections; topical cream
Oral bioavailability is low (15-30%) and decreases with increasing dose. Requires frequent dosing (3-5 times daily for oral). Can be taken with or without food. Maintain adequate hydration to prevent crystalluria, especially with IV formulation.4
Safety
Full safety detail.
Side effects
Nausea and vomiting
Diarrhea
Headache
Malaise
Renal toxicity/crystalluria (especially IV, ensure adequate hydration and slow infusion)
Neurotoxicity (tremor, confusion, especially in renal impairment)
Contraindications
Known hypersensitivity to acyclovir or valacyclovir10,1
L-lysine is used by some patients as adjunctive prophylaxis against herpes simplex recurrences, working by a different mechanism than acyclovir. Evidence is mixed and modest, but daily doses above 1-3 g have shown subjective benefit in some trials, with no known pharmacokinetic interaction with acyclovir or valacyclovir.
Recommendation: Lysine is reasonable as a complement to acyclovir for recurrent oral or genital HSV, typically at 1-3 g per day. Do not use it as a substitute for prescribed antivirals during an active outbreak.
Topical zinc sulfate has shown benefit for recurrent herpes labialis in small placebo-controlled trials, and zinc has well-documented immunomodulatory effects. Oral zinc is plausibly additive when combined with acyclovir for recurrent HSV, although high-quality combination trials are lacking. There is no known systemic pharmacokinetic interaction with acyclovir.
Recommendation: Modest oral zinc (15-25 mg/day with food) is reasonable as adjunctive support during recurrent HSV outbreaks while taking acyclovir. Do not exceed 40 mg elemental zinc daily long-term; chronic high-dose zinc causes copper deficiency.
Quercetin has demonstrated antiviral activity against HSV-1 in vitro and in animal models, primarily by interfering with viral attachment and replication. While clinical trials in HSV are lacking, the mechanism is non-overlapping with acyclovir, and combination use during recurrent outbreaks is biologically plausible and low-risk at typical supplement doses.
Recommendation: Quercetin 250-500 mg/day is reasonable as an adjunct during HSV outbreaks while taking acyclovir. Do not use quercetin as a substitute for prescribed antiviral therapy.
Ganoderma lucidum (Reishi) polysaccharides have antiviral activity against HSV-1 and HSV-2 in vitro, and a small clinical study reported faster recovery of herpes labialis and genitalis with reishi-containing formulas. Evidence for additive benefit with acyclovir is preliminary, but no pharmacokinetic interaction is established, and the combination is biologically plausible.
Recommendation: Reishi may be used as a low-risk adjunct during HSV outbreaks while taking acyclovir, but it should not replace antiviral therapy. Be aware reishi has mild antiplatelet activity at high doses; stop before surgery.
Vitamin C has in vitro antiviral activity against HSV and supports immune function, and a topical ascorbate solution showed modest benefit in recurrent mucocutaneous herpes. Evidence for additive benefit when combined with acyclovir is limited but the combination is low risk and may modestly support immune-mediated viral clearance.
Recommendation: Standard-dose vitamin C (500-1000 mg/day) is a reasonable adjunct during HSV outbreaks while taking acyclovir. Do not use high-dose vitamin C as a substitute for prescribed antivirals.
Kably B, Briard M, Francoz C et al.. Population pharmacokinetics of aciclovir and its major metabolite 9-carboxymethoxymethylguanine and safety profile of valaciclovir in early liver transplant recipients. The Journal of antimicrobial chemotherapy. 2025
Wakelin A, Wolff A, Angus-Leppan H. Is intravenous aciclovir overused in possible viral encephalitis? a retrospective review. Journal of neurology. 2025
Kabut T, Weinbergerová B, Folber F et al.. High-dose aciclovir in CMV infection prophylaxis after allogeneic HSCT: a single-center long-term experience. Bone marrow transplantation. 2023
Keller MJ, Malone AM, Carpenter CA et al.. Safety and pharmacokinetics of aciclovir in women following release from a silicone elastomer vaginal ring. The Journal of antimicrobial chemotherapy. 2012
This page is educational. Do not start, stop, or change a supplement or medication based on it without checking with a qualified healthcare professional.
Use this with your stack
Acyclovir in NutriStack.
Add it to your stack, see how it interacts with everything else you take, and get a Stack Score that updates the moment it does.
NutriStack is an informational and organizational tool, not a medical service, and not a substitute for professional advice. Always consult a qualified healthcare professional before starting, stopping, or changing any supplement or medication.
NutriStack