This page shows what was measured, who it was measured in, and what that does not settle.
What Aciclovir does in the body
The copying stops and the polymerase is left jammed on the broken chain.
Acyclovir arrives as a dud. It has to be phosphorylated — switched on — before it can do anything, and the enzyme that performs the first switch is one the herpesvirus brings with it. An uninfected cell has no such enzyme, so the drug sits there inert. Inside an infected cell it becomes acyclovir triphosphate, which the viral DNA-copying machine mistakes for a normal building block, incorporates, and then cannot continue past, because the molecule is missing the chemical hook the next letter would attach to.
Why people take it. Used for shingles, genital herpes, chickenpox and severe herpes infections.
What happened in people
For herpes infection of the brain, deaths fell from 54% with the older treatment to 28% with acyclovir.
✓ Reviewed first-read answer
Where this came from
A person wrote this and a reviewer approved it against this exact record. It carries no effect size.
A reviewer approved this against this record. The reviewed-claim record carrying the exact population and effect size does not exist yet.
No source is stored against this line.
The limit that matters most
It did not clearly prevent long-lasting pain after shingles.
Where it acts
Inside an infected cell only — the drug is switched on by a viral enzyme that uninfected cells do not have
Kind of result
The kind of result is not recorded
Supervision
RNAWiki has not recorded a supervision or regulatory status for this substance.
What the registries record it as
The substance registry classes this as chemical.
FDA substance registry · X4HES1O11F · read 2026-08-29
Its recorded molecular formula is C8H11N5O3, weighing 225.
US prescribing information · 103f29b8-2c13-4917-a446-59d3246d48d1 · read 2026-08-30
Where each sentence above came from
A person wrote this explanation into the record, with the studies named in the path below.
A reviewer approved this sentence against this exact record and its sources.
The limit a reviewer approved as the one that matters most here.
The four opening statements run to 125 words.
Words this page uses
Four words worth knowing first
Chosen from what this page shows, with each one explained before the word it depends on.
Comparator
A comparator is whatever the treatment was measured against.
A picture of it, and where the picture fails
It is like the other runner in a race.
Where that stops being true. A race has one winner. A study can show both arms improved.
What people get wrong. Results are read without asking what the other group got. Beating nothing is not beating a treatment.
The control condition against which the experimental intervention is assessed.
Randomisation
Randomisation means chance decides who gets which treatment.
A picture of it, and where the picture fails
It is like a coin toss deciding the groups.
Where that stops being true. A coin toss is fair once. Fairness here comes from doing it for everyone.
What people get wrong. It is thought to make groups identical. It makes them similar on average, including on things nobody measured.
Allocation of participants to arms by a chance process, so that unmeasured factors are balanced in expectation.
Absolute difference
An absolute difference is how many more people in a hundred were affected.
A picture of it, and where the picture fails
It is like counting heads in two rooms of a hundred.
Where that stops being true. Heads are easy to count. Study results carry a margin of error too.
What people get wrong. It is confused with a percentage change, which can look far larger.
The arithmetic difference in event rates between arms.
Confidence interval
A confidence interval is the range the true answer is likely to sit in.
A picture of it, and where the picture fails
It is like a weather forecast giving a range rather than one number.
Where that stops being true. A forecast range covers tomorrow. This one covers what the study could resolve.
What people get wrong. The middle number is read as the answer. A range crossing zero means no change is still possible.
An interval estimate that would contain the true parameter in a stated proportion of repeated studies.
What happened in people◇Read from sources, not yet reviewed
What happened in people
Each card is one study: the exact question it asked, who was in it, and whether it showed what it set out to show.
Mortality and functional outcome at six months in biopsy-proven herpes simplex encephalitis
✓ The study showed what it set out to show
Who was studied
Whitley RJ et al., N Engl J Med 1986;314:144-149 (NIAID Collaborative Antiviral Study Group)
How many people
208
Study design
Randomised, active-controlled trial against vidarabine
Compared against
Not recorded for this study
Kind of result
Living longer, or avoiding a major event
What was found
Mortality 28% on acyclovir against 54% on vidarabine (p=0.008) among 69 biopsy-proven cases; normal function at six months 38% against 14% (p=0.021)
Repeated elsewhere
Unreplicated
What this does not prove. Meeting one endpoint in one population does not carry to other goals or other people.
The limits of this study, and where it came from
Main limit. Only 69 of the 208 randomised patients (33%) had biopsy-proven disease, so the mortality comparison rests on 32 and 37 patients respectively. The result is large and the trial is small.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Oral capsule at 200 mg, tablet at 400 and 800 mg, oral suspension, intravenous infusion, topical cream and ointment, and a buccal tablet — oral dosing ranges from twice to five times daily depending on indication
Interval reported. Not recorded in this summary
Written into the record, not signed off as a reviewed claim.
Acyclovir capsules and tablets United States prescribing information — Description, Mechanism of Antiviral Action, Drug Resistance, Clinical Pharmacology, Cl… · a recorded source, not a stored snapshot
41 linked transmissions on acyclovir against 43 on placebo; hazard ratio 0.92 (95% CI 0.60 to 1.41), p=0.69
Repeated elsewhere
Replicated
What this does not prove. A study that did not show an effect does not show that no effect exists anywhere.
The limits of this study, and where it came from
Main limit. Every intermediate measure moved as predicted — HSV-2-positive genital ulcers fell 73% (RR 0.27, 95% CI 0.20 to 0.36) and mean plasma HIV-1 fell 0.25 log10 copies/mL — with 96% adherence and 92% retention at 24 months. The null result is a mechanism result, not an execution failure.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Oral capsule at 200 mg, tablet at 400 and 800 mg, oral suspension, intravenous infusion, topical cream and ointment, and a buccal tablet — oral dosing ranges from twice to five times daily depending on indication
Interval reported. 95% CI 0
Written into the record, not signed off as a reviewed claim.
Acyclovir capsules and tablets United States prescribing information — Description, Mechanism of Antiviral Action, Drug Resistance, Clinical Pharmacology, Cl… · a recorded source, not a stored snapshot
HIV-1 incidence 3.9 per 100 person-years on aciclovir against 3.3 on placebo; hazard ratio 1.16 (95% CI 0.83 to 1.62)
Repeated elsewhere
Replicated
What this does not prove. A study that did not show an effect does not show that no effect exists anywhere.
The limits of this study, and where it came from
Main limit. Genital ulcers on examination fell 47% and HSV-2-positive ulcers 63%. Adherence was 94% in both arms. The point estimate favours placebo.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Oral capsule at 200 mg, tablet at 400 and 800 mg, oral suspension, intravenous infusion, topical cream and ointment, and a buccal tablet — oral dosing ranges from twice to five times daily depending on indication
Interval reported. 95% CI 0
Written into the record, not signed off as a reviewed claim.
Acyclovir capsules and tablets United States prescribing information — Description, Mechanism of Antiviral Action, Drug Resistance, Clinical Pharmacology, Cl… · a recorded source, not a stored snapshot
Acyclovir 71.2% against 75.7% at 3 months (adjusted p=0.50) and 85.4% against 90.8% at 9 months (adjusted p=0.10). Prednisolone, in the same trial, 83.0% against 63.6% (p<0.001) and 94.4% against 81.6% (p<0.001)
Repeated elsewhere
Replicated
What this does not prove. A study that did not show an effect does not show that no effect exists anywhere.
The limits of this study, and where it came from
Main limit. Both acyclovir point estimates favour the control arm. The authors report no evidence of benefit from acyclovir alone and no additional benefit when added to prednisolone.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Oral capsule at 200 mg, tablet at 400 and 800 mg, oral suspension, intravenous infusion, topical cream and ointment, and a buccal tablet — oral dosing ranges from twice to five times daily depending on indication
Interval reported. Not recorded in this summary
Written into the record, not signed off as a reviewed claim.
Acyclovir capsules and tablets United States prescribing information — Description, Mechanism of Antiviral Action, Drug Resistance, Clinical Pharmacology, Cl… · a recorded source, not a stored snapshot
RNAWiki holds 4 written-up human studies for this substance, each with the question it asked.
How we know it
Each card names the study, the number of people and what the study set out to measure.
What this does not prove
These summaries were written by a person and have not been signed off as reviewed claims.
Why it matters
A study that failed is as informative as one that worked, and both are here.
What we still do not know
No reviewed claim exists, so no exact population, effect size or interval is published yet.
What it changes in the body◇Read from sources, not yet reviewed
The path through the body
From what a person takes to what changes. A solid line is a step measured in people. A dashed line is a step nobody has measured that way.
Start
Aciclovir
What a person takes: Oral capsule at 200 mg, tablet at 400 and 800 mg, oral suspension, intravenous infusion, topical cream and ointment, and a buccal tablet — oral dosing ranges from twice to five times daily depending on indication.
The measurement behind this step
Oral absorption is incomplete and saturable: the label states plasma concentrations rise less than dose proportionally, and that the fall in bioavailability depends on the dose rather than the formulation. Food does not affect absorption. Half-life and total body clearance both depend on renal function, and plasma concentrations are higher in older people because of age-related decline in it. In children aged seven months to seven years, mean half-life after 300 to 600 mg/m² was 2.6 hours.
Getting in
A pro-drug that most of the gut ignores
Only a fraction of a swallowed dose reaches the blood, and the fraction gets smaller as the dose gets bigger. That is why the shingles regimen is five capsules a day.
──Measured in people. Written by a person from the study named beside the step. Not signed off as a reviewed claim.
The measurement behind this step
The label states that increases in plasma acyclovir concentration are less than dose proportional with increasing dose, and that the decrease in bioavailability is a function of the dose and not the dosage form. Food has no effect on absorption. The only known urinary metabolite is 9-[(carboxymethoxy)methyl]guanine; the rest is excreted unchanged by the kidney.
Acyclovir capsules and tablets United States prescribing information — Description, Mechanism of Antiviral Action, Drug Resistance, Clinical Pharmacology, Cl… · a recorded source, not a stored snapshot
The drug arrives inert. A herpes enzyme performs the first chemical step that activates it — and uninfected cells do not have that enzyme.
╌╌Described, with no measurement named. No measurement is named for this step, so it is drawn as an unconfirmed link.
The measurement behind this step
The label attributes the highly selective inhibitory activity to affinity for the thymidine kinase encoded by HSV and VZV, which converts acyclovir into acyclovir monophosphate. Greater activity against HSV than VZV reflects more efficient phosphorylation by the HSV enzyme.
Acyclovir capsules and tablets United States prescribing information — Description, Mechanism of Antiviral Action, Drug Resistance, Clinical Pharmacology, Cl… · a recorded source, not a stored snapshot
Two more phosphates are added by the cell’s own enzymes, turning the drug into a counterfeit DNA building block.
╌╌Described, with no measurement named. No measurement is named for this step, so it is drawn as an unconfirmed link.
The measurement behind this step
Cellular guanylate kinase converts the monophosphate to the diphosphate and a number of cellular enzymes complete the conversion to acyclovir triphosphate. The triphosphate accumulates selectively in infected cells because only they perform the first step.
Acyclovir capsules and tablets United States prescribing information — Description, Mechanism of Antiviral Action, Drug Resistance, Clinical Pharmacology, Cl… · a recorded source, not a stored snapshot
The virus’s DNA-copying enzyme grabs the fake letter, attaches it, and then finds there is nothing to attach the next letter to.
╌╌Described, with no measurement named. No measurement is named for this step, so it is drawn as an unconfirmed link.
The measurement behind this step
The label describes three simultaneous actions: competitive inhibition of viral DNA polymerase, incorporation into and termination of the growing viral DNA chain, and inactivation of the viral DNA polymerase. The termination is obligate because the acyclic side chain has no 3′ hydroxyl.
Acyclovir capsules and tablets United States prescribing information — Description, Mechanism of Antiviral Action, Drug Resistance, Clinical Pharmacology, Cl… · a recorded source, not a stored snapshot
Lesions scab and heal sooner and shedding stops sooner. Nothing about the treatment removes the latent virus sitting in the nerve.
╌╌Described, with no measurement named. No measurement is named for this step, so it is drawn as an unconfirmed link.
The measurement behind this step
In the zoster trials the label reports shortened times to lesion scabbing, healing and complete cessation of acute pain, reduced viral shedding and reduced new lesion formation, with treatment started within 72 hours and greatest benefit within 48. In the chickenpox trials in 993 children the drug shortened time to 50% healing and reduced maximum lesion count, and did not affect varicella-zoster-specific humoral or cellular immune responses at one month or one year.
Acyclovir capsules and tablets United States prescribing information — Description, Mechanism of Antiviral Action, Drug Resistance, Clinical Pharmacology, Cl… · a recorded source, not a stored snapshot
Two large trials showed that cutting herpes ulcers sharply had no effect on HIV transmission or acquisition. The intermediate step moved; the thing that mattered did not.
──Measured in people. Written by a person from the study named beside the step. Not signed off as a reviewed claim.
The measurement behind this step
Partners in Prevention: HSV-2-positive genital ulcers down 73% (RR 0.27) and plasma HIV-1 down 0.25 log10, with linked HIV-1 transmission hazard ratio 0.92 (95% CI 0.60 to 1.41, p=0.69) in 3,408 couples. HPTN 039: genital ulcers down 47%, HIV-1 acquisition hazard ratio 1.16 (95% CI 0.83 to 1.62) in 3,172 participants.
Acyclovir capsules and tablets United States prescribing information — Description, Mechanism of Antiviral Action, Drug Resistance, Clinical Pharmacology, Cl… · a recorded source, not a stored snapshot
No suggested links are held for this record, so nothing is hidden from this path.
What we know
The record describes 6 steps from taking it to an effect in a person.
How we know it
Each step names the study behind it in the technical detail beside it.
What this does not prove
A change inside the body is a reason to look. It is not a result in a person.
Why it matters
A reader can see exactly where the chain stops being measured in people.
What we still do not know
No reviewed claim binds any of these steps to a named population.
What is missing or unclear◇Read from sources, not yet reviewed
Were people like you studied?
RNAWiki cannot tell whether a study fits you. It can show who was in it, and where the result stops carrying.
Who was studied
People similar to this profile were included.
People with shingles, with first or recurrent genital herpes, or with chickenpox; and, by injection, people with herpes encephalitis, neonatal herpes or severe disease while immunosuppressed.
Who is missing from the studies
Which groups were under-represented in the studies has not been recorded for this substance. Pregnancy, breastfeeding, children, older adults, and people with liver or kidney conditions are commonly excluded from trials; nothing here says whether they were.
What the label states about particular groups
On pediatric, the label states: “Safety and effectiveness in pediatric patients less than 12 years of age have not been established.”
US prescribing information · 103f29b8-2c13-4917-a446-59d3246d48d1 · read 2026-08-30
On older people, the label states: “Clinical studies of acyclovir cream did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects.”
US prescribing information · 103f29b8-2c13-4917-a446-59d3246d48d1 · read 2026-08-30
On people who are pregnant, the label states: “Risk Summary Acyclovir is minimally absorbed systemically following topical route of administration, and maternal use is not expected to result in fetal exposure to the Acyclovir Cream [see Clinical Pharmacology (12.3) ] .”
US prescribing information · 103f29b8-2c13-4917-a446-59d3246d48d1 · read 2026-08-30
On people who are breastfeeding, the label states: “Risk Summary Acyclovir is minimally absorbed systemically following topical route of administration, and breastfeeding is not expected to result in exposure of the child to Acyclovir Cream [see Clinical Pharmacology (12.3) ] .”
US prescribing information · 103f29b8-2c13-4917-a446-59d3246d48d1 · read 2026-08-30
Where the result stopped carrying
HIV-1 transmission was unchanged despite a 73% reduction in the genital ulcers that were supposed to mediate it
HIV-1 acquisition was, if anything, slightly higher on aciclovir than on placebo in HPTN 039
Postherpetic neuralgia was not significantly reduced at four or six months in pooled randomised trials
Bell’s palsy recovery was not improved, with both point estimates favouring no acyclovir
This is a scope explorer, not a diagnosis engine.
It shows who was studied so you can see whether people similar to you were included.
RNAWiki cannot tell whether a study fits you. It can show who was in it.
What it would be like to take◇Read from sources, not yet reviewed
Why it might seem to do nothing
A real effect and a noticed effect are different things. These are the recorded reasons the two come apart.
It was studied in different people
The people in the studies were not much like the reader.
On this record: Which groups were under-represented in the studies has not been recorded for this substance. Pregnancy, breastfeeding, children, older adults, and people with liver or kidney conditions are commonly excluded from trials; nothing here says whether they were.
There was nothing to correct
Where a level is already normal, topping it up may change nothing.
On this record: Resistance remains concentrated in immunocompromised patients and is almost always thymidine kinase deficiency, which confers cross-resistance to famciclovir as well
The evidence may simply be wrong
Small early studies often do not hold up.
On this record: RNAWiki has not yet published a reviewed conclusion for this use.
Other reasons RNAWiki checked and found nothing for (10)
It was studied for a different goal
The studies measured something else entirely. Nothing in this record points to this reason.
A different form was studied
The studied form is not the form on the shelf. Nothing in this record points to this reason.
Something else had to happen too
In the studies it was paired with training, a diet or another treatment. Nothing in this record points to this reason.
The change is too small to feel
A real change can still sit below what a person notices. Nothing in this record points to this reason.
Day-to-day swing hides it
Sleep, food, stress and time of day move most numbers more than this would. Nothing in this record points to this reason.
Not enough time yet
The studies ran longer than the person has waited. Nothing in this record points to this reason.
It was not taken as studied
Missed days change the result, and studies count them. Nothing in this record points to this reason.
Something else changed at the same time
Two changes at once cannot be told apart afterwards. Nothing in this record points to this reason.
The product may not be what it says
Contents of a sold product are not always what the label states. Nothing in this record points to this reason.
No recorded reason
RNAWiki has nothing stored that would explain it. Nothing in this record points to this reason.
None of these is a reason to take more. Taking more is not a step this page ever suggests.
What it would be like to take◇Read from sources, not yet reviewed
What taking it involves
The recorded facts about getting hold of it and using it. Nothing here is a suggestion about what you should do.
How it is supplied
Given by a clinician
❝ Quoted from a source
Where this came from
Copied from a source RNAWiki stored, with the source named.
Read from the recorded approval status.
No source is stored against this line.
Form and route
Oral capsule at 200 mg, tablet at 400 and 800 mg, oral suspension, intravenous infusion, topical cream and ointment, and a buccal tablet — oral dosing ranges from twice to five times daily depending on indication
✎ Source-linked record
Where this came from
A person wrote this into the record with the study named beside it. No reviewer has signed it off.
The form and route recorded on this substance.
No source is stored against this line.
Who oversees it
RNAWiki has not recorded a supervision or regulatory status for this substance.
❝ Quoted from a source
Where this came from
Copied from a source RNAWiki stored, with the source named.
No register row and no identity class settled the question.
No source is stored against this line.
What is in the pack
Oral absorption is incomplete and saturable: the label states plasma concentrations rise less than dose proportionally, and that the fall in bioavailability depends on the dose rather than the formulation. Food does not affect absorption. Half-life and total body clearance both depend on renal function, and plasma concentrations are higher in older people because of age-related decline in it. 6 hours.
✎ Source-linked record
Where this came from
A person wrote this into the record with the study named beside it. No reviewer has signed it off.
Recorded notes on how this is sold and what that means for what is in the pack.
No source is stored against this line.
Where it is registered
Regulatory records are listed in the technical disclosure at the foot of this page.
# Counted from records
Where this came from
A count of rows RNAWiki holds. It describes our records, not your body.
Register entries are stored per jurisdiction and shown with their dates.
No source is stored against this line.
Why people stop
Not recorded.
∅ Nothing recorded
Where this came from
RNAWiki holds nothing here and says so rather than guessing.
No record of why people stopped taking it is stored for this substance.
No source is stored against this line.
What it would be like to take◇Read from sources, not yet reviewed
What can go wrong
Sorted by where each line came from. A regulator's label and a report somebody sent in are not the same kind of fact.
·Worth asking a clinician aboutWritten into the record from the studies named on this page
The label warns that renal failure, in some cases resulting in death, has been observed with acyclovir therapy — the drug is poorly soluble at 2.5 mg/mL in water at 37°C and can crystallise in renal tubules, particularly with rapid intravenous administration or dehydration. It also warns that thrombotic thrombocytopenic purpura and haemolytic uraemic syndrome, which have resulted in death, have occurred in immunocompromised patients receiving acyclovir. Dose reduction is required in renal impairment. Probenecid raises acyclovir exposure by reducing renal clearance. Resistant isolates, almost always thymidine kinase-deficient, are recovered from immunocompromised patients and can cause severe disease in infants and immunocompromised adults.
Nobody counted how many people took this and were fine, so this cannot be turned into a rate.
Where this came from
Acyclovir capsules and tablets United States prescribing information — Description, Mechanism of Antiviral Action, Drug Resistance, Clinical Pharmacology, Cl… · a recorded source, not a stored snapshot
Over a long time. No completed tested study window is recorded, so long-term effects are not established by the registry record.
Groups the studies covered thinly. Which groups were under-represented in the studies has not been recorded for this substance. Pregnancy, breastfeeding, children, older adults, and people with liver or kidney conditions are commonly excluded from trials; nothing here says whether they were.
What is missing or unclear◇Read from sources, not yet reviewed
Does the exact form matter?
Evidence belongs to the exact thing that was tested. A different salt, a different mixture or a different preparation is a different question.
The form that was studied
Oral capsule at 200 mg, tablet at 400 and 800 mg, oral suspension, intravenous infusion, topical cream and ointment, and a buccal tablet — oral dosing ranges from twice to five times daily depending on indication
✎ Source-linked record
Where this came from
A person wrote this into the record with the study named beside it. No reviewer has signed it off.
The form used in the studies cited on this page.
No source is stored against this line.
What is sold
Food does not affect absorption. Half-life and total body clearance both depend on renal function, and plasma concentrations are higher in older people because of age-related decline in it. 6 hours.
✎ Source-linked record
Where this came from
A person wrote this into the record with the study named beside it. No reviewer has signed it off.
Recorded notes on which forms are sold and how they compare.
No source is stored against this line.
What is recorded as being sold
232 products list this as an active ingredient in the United States drug directory. 231 of them contain it and nothing else.
FDA National Drug Code directory · 72162-1735 · read 2026-08-29
They are sold as capsule, cream, injection, powder, lyophilized, for solution, injection, solution, ointment and powder, taken cutaneous, intravenous, ophthalmic and oral.
FDA National Drug Code directory · 72162-1735 · read 2026-08-29
The regulator's established pharmacologic class for it is dna polymerase inhibitors [moa], herpes simplex virus nucleoside analog dna polymerase inhibitor [epc] and herpes zoster virus nucleoside analog dna polymerase inhibitor [epc].
FDA National Drug Code directory · 72162-1735 · read 2026-08-29
181 published labels name it as an active ingredient. 180 of them describe this substance alone, which is where its own label text on this page comes from.
US prescribing information · a1086845-ba08-4fb2-81dc-aea9c68bf2c3 · read 2026-08-29
Those labels are classed as human prescription drug.
US prescribing information · a1086845-ba08-4fb2-81dc-aea9c68bf2c3 · read 2026-08-29
Acyclovir is capsules at 200 mg, recorded as prescription product; fda label in effect 2024-09-05 in the United States.
US prescribing information · 01ae85df-d1a0-44f7-b4c0-0ac74d2216d4 · read 2026-08-27
Recorded price in US: 0.06936 USD per one millilitre, across 7 priced products whose strengths and pack forms differ, as of 2026-08-26, paid by retail pharmacies buying the product, as surveyed by the Centers for Medicare & Medicaid Services. It is not a list price, an insurance price, or what anyone pays at a counter..
Recorded source · 2026-08-26 · read 2026-08-28
Recorded price in US: 0.09733–0.1847 USD per one unit as the pricing file counts it — a tablet, capsule, patch or single item, across 49 priced products whose strengths and pack forms differ, as of 2026-08-26, paid by retail pharmacies buying the product, as surveyed by the Centers for Medicare & Medicaid Services. It is not a list price, an insurance price, or what anyone pays at a counter..
Recorded source · 2026-08-26 · read 2026-08-28
Recorded price in US: 0.34213–9.10761 USD per one gram, across 21 priced products whose strengths and pack forms differ, as of 2026-08-26, paid by retail pharmacies buying the product, as surveyed by the Centers for Medicare & Medicaid Services. It is not a list price, an insurance price, or what anyone pays at a counter..
Recorded source · 2026-08-26 · read 2026-08-28
Evidence carries across two names for one substance. It does not carry across a salt, a mirror form or a mixture.
What it would be like to take◇Read from sources, not yet reviewed
What you could measure
This one is decided with a clinician, so this section holds questions to ask rather than a plan to run.
RNAWiki could not confidently classify this substance, so no self-experiment plan is offered.
Questions worth asking
Which of the trials of Aciclovir studied people like me?
What was measured, and for how long?
Was the result a laboratory value or a health outcome?
What would we watch for, and when would we stop?
Tracking can show whether something changed for you. It cannot show what caused it.
RNAWiki records evidence. It does not say whether this substance is right for you.
What is missing or unclear◇Read from sources, not yet reviewed
Claims that go past the evidence
Things said about this substance that sound reasonable, and the exact step that is missing between the evidence and the claim.
✗Goes past the evidence
That suppressing herpes reactivation reduces HIV transmission or acquisition — two large randomised trials found hazard ratios of 0.92 and 1.16
Why it sounds right. It follows from something real on this page: a body step, an animal result or a related finding.
The missing step. Nobody measured this in people for this use, or the study that did measure it did not show it.
What would change this
A study in people, for this exact use, measuring this exact thing, that a reviewer signs off.
RNAWiki has not yet published a reviewed conclusion for this use.
✗Goes past the evidence
That treating the acute shingles rash prevents postherpetic neuralgia — pooled trials found RR 0.75 (0.51 to 1.11) at four months and 1.05 (0.87 to 1.27) at six
Why it sounds right. It follows from something real on this page: a body step, an animal result or a related finding.
The missing step. Nobody measured this in people for this use, or the study that did measure it did not show it.
What would change this
A study in people, for this exact use, measuring this exact thing, that a reviewer signs off.
RNAWiki has not yet published a reviewed conclusion for this use.
✗Goes past the evidence
That a herpesvirus aetiology for Bell’s palsy makes an antiviral useful for it — the factorial trial found no benefit alone or added to prednisolone
Why it sounds right. It follows from something real on this page: a body step, an animal result or a related finding.
The missing step. Nobody measured this in people for this use, or the study that did measure it did not show it.
What would change this
A study in people, for this exact use, measuring this exact thing, that a reviewer signs off.
RNAWiki has not yet published a reviewed conclusion for this use.
✗Goes past the evidence
That the rising year-on-year recurrence-free rates during suppression show increasing efficacy, when the study had no concurrent untreated arm and recurrence frequency falls naturally over time
Why it sounds right. It follows from something real on this page: a body step, an animal result or a related finding.
The missing step. Nobody measured this in people for this use, or the study that did measure it did not show it.
What would change this
A study in people, for this exact use, measuring this exact thing, that a reviewer signs off.
RNAWiki has not yet published a reviewed conclusion for this use.
What is missing or unclear◇Read from sources, not yet reviewed
What nobody knows yet
Open questions, each with why it is open and what would close it.
Missing populations
Which groups were under-represented in the studies has not been recorded.
Why it matters. Recorded by the evidence model as a gap on this record.
What would answer it
A study that measures it, and a reviewer to sign it off.
Last checked 2026-09-04. Searched: The sources listed in the receipts at the foot of this page.
Missing long-term data
No completed tested study window is recorded.
Why it matters. Recorded by the evidence model as a gap on this record.
What would answer it
A study that measures it, and a reviewer to sign it off.
Last checked 2026-09-04. Searched: The sources listed in the receipts at the foot of this page.
No reviewed conclusion
RNAWiki has not yet published a reviewed conclusion for this use.
Why it matters. Recorded by the evidence model as a gap on this record.
What would answer it
A study that measures it, and a reviewer to sign it off.
Last checked 2026-09-04. Searched: The sources listed in the receipts at the foot of this page.
Missing interaction studies
No interaction was found in the registers checked. Not finding one is not the same as showing there is none.
Why it matters. Recorded by the evidence model as a gap on this record.
What would answer it
A study that measures it, and a reviewer to sign it off.
Last checked 2026-09-04. Searched: The sources listed in the receipts at the foot of this page.
Formulation uncertainty
Several salts, forms or products of Aciclovir are recorded. Results from one form may not transfer to another.
Why it matters. Recorded by the evidence model as a gap on this record.
What would answer it
A study that measures it, and a reviewer to sign it off.
Last checked 2026-09-04. Searched: The sources listed in the receipts at the foot of this page.
Mechanism not reviewed
No reviewed mechanism story exists for this substance.
Why it matters. Recorded by the evidence model as a gap on this record.
What would answer it
A study that measures it, and a reviewer to sign it off.
Last checked 2026-09-04. Searched: The sources listed in the receipts at the foot of this page.
What happened in people◇Read from sources, not yet reviewed
Check any of this yourself
Every line above traced back to the study it came from. This is the technical layer, and the vocabulary changes here.
Every line above can be traced to the study named beside it. Follow the link and read it.
Halved mortality in herpes encephalitis
In plain words
In the trial that established it, people with biopsy-proven herpes encephalitis died at 28% on acyclovir against 54% on the drug it replaced. More than twice as many were functioning normally six months later.
What was measured
Six-month mortality and functional recovery in biopsy-proven herpes simplex encephalitis
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
Two hundred and eight patients undergoing brain biopsy for presumptive herpes simplex encephalitis were randomised to vidarabine 15 mg/kg/day or acyclovir 30 mg/kg/day for ten days. Sixty-nine (33%) had biopsy-proven disease: 37 on vidarabine, 32 on acyclovir. Mortality was 54% on vidarabine against 28% on acyclovir (p=0.008). Stratified by Glasgow coma score at the start of treatment — above 10, 7 to 10, and 6 or below — six-month mortality was 42%, 46% and 67% on vidarabine against 0%, 25% and 25% on acyclovir. At six months, 12 of 32 acyclovir recipients (38%) were functioning normally against 5 of 37 on vidarabine (14%), p=0.021. This is a hard-endpoint result in a small trial with an active comparator, and it is the strongest single piece of evidence the molecule has.
Written into the record, not signed off as a reviewed claim
Genital ulcers fell 73%. HIV transmission did not move.
In plain words
The reasoning was airtight: herpes sores raise HIV transmission, so suppressing herpes should lower it. In 3,408 African couples, acyclovir cut herpes ulcers by nearly three-quarters and lowered HIV levels in blood — and transmitted HIV at exactly the same rate as placebo.
What was measured
Genetically linked HIV-1 transmission within serodiscordant couples over 24 months
Effect estimate
No reviewed effect estimate exists for this record.
Limits
This entry records a failure.
From the source
A randomised placebo-controlled trial enrolled 3,408 serodiscordant couples at 14 African sites in which the HIV-1-positive partner was also HSV-2-positive, had a CD4 count of 250 or above, and was not on antiretroviral therapy. The intervention was acyclovir 400 mg twice daily. Of 132 HIV-1 seroconversions after randomisation (2.7 per 100 person-years), 84 were genetically linked within couples: 41 on acyclovir and 43 on placebo, hazard ratio 0.92 (95% CI 0.60 to 1.41, p=0.69). The drug did what it was supposed to do at every intermediate step: HSV-2-positive genital ulcers fell 73% (risk ratio 0.27, 95% CI 0.20 to 0.36, p<0.001) and mean plasma HIV-1 fell by 0.25 log10 copies/mL (95% CI 0.22 to 0.29, p<0.001). Adherence to dispensed drug was 96% and 92% of the index partners remained in the study for 24 months, so the null result cannot be explained away as a failure of execution. Both surrogates moved. The outcome did not.
Written into the record, not signed off as a reviewed claim
And it did not stop people acquiring HIV either
In plain words
The companion trial asked the other half of the question: does suppressing herpes protect an uninfected person from catching HIV? In 3,172 participants the answer was no, with the numbers pointing slightly the wrong way.
What was measured
HIV-1 acquisition over 12 to 18 months of herpes suppressive therapy
Effect estimate
No reviewed effect estimate exists for this record.
Limits
This entry records a failure.
From the source
A double-blind randomised placebo-controlled phase 3 trial in HIV-negative, HSV-2-seropositive women in Africa and men who have sex with men in Peru and the United States assigned participants to aciclovir 400 mg twice daily (n=1,637) or placebo (n=1,640) for 12 to 18 months. In the 3,172-participant primary dataset, HIV-1 incidence was 3.9 per 100 person-years on aciclovir (75 events in 1,935 person-years) against 3.3 on placebo (64 events in 1,969 person-years), hazard ratio 1.16 (95% CI 0.83 to 1.62). Genital ulcers on examination fell 47% (relative risk 0.53, 0.46 to 0.62) and HSV-2-positive ulcers 63% (0.37, 0.31 to 0.45). Adherence was 94% in both arms and retention 85% at 18 months in both. Two independently designed trials, one on transmission and one on acquisition, in different populations on two continents, both reduced the surrogate substantially and neither moved the outcome. Registered as NCT00076232.
Written into the record, not signed off as a reviewed claim
It does not prevent the nerve pain that follows shingles
In plain words
The thing people fear after shingles is the pain that outlasts the rash. Pooled randomised trials found acyclovir did not significantly reduce it at four months or at six.
What was measured
That treating the acute shingles rash with acyclovir prevents postherpetic neuralgia — an inference the pooled randomised evidence does not support at four or six months
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
A Cochrane review of randomised trials of antiviral treatment started within 72 hours of the herpes zoster rash identified six eligible trials in 1,211 participants, five of oral aciclovir and one of famciclovir. Pooling three trials in 609 participants, there was no significant difference between aciclovir and control in the incidence of postherpetic neuralgia four months after rash onset (risk ratio 0.75, 95% CI 0.51 to 1.11), and none at six months across two trials in 476 participants (risk ratio 1.05, 95% CI 0.87 to 1.27). The FDA label describes what the zoster trials did show: shortened time to lesion scabbing and healing, shortened time to complete cessation of pain during the acute episode, reduced duration of viral shedding and new lesion formation, and reduced prevalence of localised zoster-associated neurological symptoms. Faster healing of the acute episode is measured. Prevention of the chronic pain syndrome is not, and the pooled data do not support it.
Written into the record, not signed off as a reviewed claim
No benefit in Bell’s palsy, alone or added to a steroid
In plain words
Facial palsy was widely treated with acyclovir on the theory that a herpesvirus causes it. A 551-patient factorial trial found the steroid worked and the antiviral did not, either by itself or added on top.
What was measured
Complete recovery of facial function on the House-Brackmann scale at 3 and 9 months
Effect estimate
No reviewed effect estimate exists for this record.
Limits
This entry records a failure.
From the source
A double-blind placebo-controlled factorial trial randomised 551 patients with Bell’s palsy within 72 hours of symptom onset to ten days of prednisolone, acyclovir, both, or placebo, with final outcomes assessed for 496. At three months, complete recovery of facial function on the House-Brackmann scale was 83.0% with prednisolone against 63.6% without (p<0.001), and 71.2% with acyclovir against 75.7% without (adjusted p=0.50). At nine months it was 94.4% against 81.6% for prednisolone (p<0.001) and 85.4% against 90.8% for acyclovir (adjusted p=0.10). The authors conclude there is no evidence of benefit from acyclovir given alone, and no additional benefit from adding it to prednisolone. Both acyclovir point estimates favour the control arm, which is not the same as harm and is not what a widely used treatment is expected to produce.
Written into the record, not signed off as a reviewed claim
Suppression works, and the label reports it decaying over three years
In plain words
Taken daily, it keeps most people free of genital herpes recurrences. The label reports the proportion staying recurrence-free rising each year — 45%, then 52%, then 63% — which is the natural history improving, not the drug getting stronger.
What was measured
Proportion of patients free of genital herpes recurrence during each of three years of continuous suppressive therapy
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
The label states that in double-blind placebo-controlled studies in patients with six or more recurrences a year, daily oral acyclovir given for four months to ten years prevented or reduced the frequency or severity of recurrences in more than 95% of patients. In a three-year study of acyclovir 400 mg twice daily, 45%, 52% and 63% of patients remained free of recurrences in the first, second and third years respectively, and serial three-month analyses showed 71% to 87% recurrence-free in each quarter. The rising annual figures are usually read as increasing efficacy; the more defensible reading is that genital herpes recurrence frequency falls naturally over years, so the same drug in the same people produces a better-looking number each year. That is a confound the label reports and does not resolve, because the study had no concurrent untreated arm running for three years.
Source
Acyclovir capsules United States prescribing information, Clinical Trials — Recurrent Genital Herpes
Role in the trial
Not matched to a registered study
Identity check
no open identity hold
Audit mark
caution
Review state
Written into the record, not signed off as a reviewed claim
Resistance is a problem of the immunocompromised, and it is built into the mechanism
In plain words
The same feature that makes acyclovir safe — it needs a viral enzyme to switch it on — is the feature that lets the virus escape. A virus that discards that enzyme becomes untouchable by the drug.
What was measured
Thymidine kinase-deficient acyclovir-resistant clinical isolates recovered from immunocompromised patients
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
The label states that resistance can result from qualitative and quantitative changes in the viral thymidine kinase or DNA polymerase, that clinical isolates with reduced susceptibility have been recovered from immunocompromised patients especially in advanced HIV infection, and that most acyclovir-resistant mutants isolated so far are thymidine kinase-deficient. It adds that thymidine kinase-negative mutants may cause severe disease in infants and immunocompromised adults. The selectivity mechanism and the resistance mechanism are the same event viewed from two sides: the drug is inert without viral thymidine kinase, and a virus without viral thymidine kinase is invisible to the drug. It also means every drug that shares the activation step — famciclovir and penciclovir — shares the cross-resistance, and escaping it requires a molecule that does not need viral activation at all.
Source
Acyclovir capsules United States prescribing information, Mechanism of Antiviral Action and Drug Resistance
Role in the trial
Not matched to a registered study
Identity check
no open identity hold
Audit mark
caution
Review state
Written into the record, not signed off as a reviewed claim
How many documents were read
178 documents were read for this substance.
RNAWiki source record
133 of them state the same halfLife, and they agree.
RNAWiki source record
121 of them state the same bioavailability, and they agree.
RNAWiki source record
142 of them state the same proteinBinding, and they agree.
RNAWiki source record
Where else this substance is registered
FDA substance identifier (UNII)
X4HES1O11F
CAS registry number
59277-89-3
PubChem compound
135398513
RxNorm concept
281
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Trial roles classified for highlighted evidence
No registered study is classified as testing this substance.
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Safety mode resolved
No register row and no identity class settled the question.
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Canonical metadata present
slug and display name present
What is missing or unclear◇Read from sources, not yet reviewed
How this medicine reached us
Kept near the foot of the page. A historical event moves up only when it changes something about this substance today.
Withdrawn in United States, 2021, for "Crystallization: customer complaints for crystallization in finished product." (openFDA drug enforcement Class I recall)
What the approval register records
100 approved applications cover products containing this substance. The earliest was NDA018604, approved 19820329 to BAUSCH.
This order is fixed in code and does not count clicks or time on the page.
What is not here
7 questions this page could not answer
These sections were prepared and left out because there was nothing to put in them. They are listed rather than hidden, so the gaps in this record are visible.
What was measured, goal by goal — found nothing in the sources checked.
How close this is to real life — found nothing in the sources checked.
Felt, measured, or meaningful — found nothing in the sources checked.
How long anything takes — found nothing in the sources checked.
What it may clash with — found nothing in the sources checked.
Other ways to the same goal — found nothing in the sources checked.
What changed on this page — found nothing in the sources checked.
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Everything above is built from what is below. This layer keeps the technical vocabulary, record identifiers and every stored row, so a reader who wants to check the page can.
The older medicine-wide conclusion held in this record
Written for a clinical reader, and about the medicine as a whole rather than about one indication, population and set of trials. RNAWiki does not treat it as a programme conclusion and no reviewer has signed it off in that form. It is here word for word because it is what the record holds.
A nucleoside analogue that only becomes active inside a herpes-infected cell, which cut mortality in biopsy-proven herpes simplex encephalitis from 54% to 28% against the previous standard in a 208-patient trial — and which, in 3,408 African couples, reduced herpes genital ulcers by 73% while doing nothing at all to HIV transmission (hazard ratio 0.92, p=0.69).
Recorded evidence blocks (10)
Q1
On the Aciclovir label: indicated for what?
"Herpes Zoster Infections: Acyclovir is indicated for the acute treatment of herpes zoster (shingles). Genital Herpes: Acyclovir is indicated for the treatment of initial episodes and the management of recurrent episodes of genital herpes.": indications and usage on Aciclovir's label. DailyMed label · e5e99a6b-79a6-7fdb-e053-2a95a90a8563 · 2026-08-26
Q2
82 registered trials of Aciclovir — at which phases?
"Investigator relocated and study funding ended."; 3 of 82 registered studies
Show the evidence
Trial
NCT00495716
terminated; "Investigator relocated and study funding ended."
NCT02349828
withdrawn; "PI decided to stop due to divisional reorganization. No pts enrolled."
NCT03368664
terminated; "Enrolment formally closed earlier than planned due to recruitment challenges."
recorded 2026-09-01 · last checked 2026-09-04
Q4
Human studies of Aciclovir used sugar pills, manufactured to mimic the Acyclovir 400 mg tablets. — over how long?
Human studies of Aciclovir used "sugar pills, manufactured to mimic the Acyclovir 400 mg tablets." ClinicalTrials.gov · 2026-09-01
12 recorded entries; human; also "5% Zovirax® cream", "5% Aciclovir cream 1A Pharma", "5% Zovirax Cold Sore Cream"
Show the evidence
human
NCT01729767
sugar pills, manufactured to mimic the Acyclovir 400 mg tablets.
NCT02711267
5% Zovirax® cream
NCT02711267
5% Aciclovir cream 1A Pharma
NCT02711267
5% Zovirax Cold Sore Cream
NCT02711267
5% Zovirax® cream (Austria)
NCT03159845
Acyclovir 400 MG
6 more recorded rows
humanNCT03656965
Acyclovir 800 MG
humanNCT04988646
Acyclovir 200 MG
humanNCT04988646
Zovirax 200 MG Tablet
humanNCT04988646
Zovirax 400 MG Tablet
humanNCT06228430
Acyclovir 800 mg Tablet
humanNCT06228430
Zovirax™ 800 mg Tablet
recorded 2026-09-01 · last checked 2026-09-04
Q5
Aciclovir's half-life is 2.5 to 3.3 hr — which schedules were studied?
2.5 to 3.3 hr, the half-life Aciclovir's label states: "Acyclovir Pharmacokinetic Characteristics (Range) Parameter Range Plasma protein binding 9 % to 33% Plasma elimination half-life 2.5 to 3.3 hr Average oral bio availability 10 % to 20 % * * Bio availability decreases with increasing dose." DailyMed label · e5e99a6b-79a6-7fdb-e053-2a95a90a8563 · 2026-08-26
Show the evidence
half lifepharmacokinetics
2.5 to 3.3 hr; Acyclovir Pharmacokinetic Characteristics (Range) Parameter Range Plasma protein binding 9 % to 33% Plasma elimination half-life 2.5 to 3.3 hr Average oral bio availability 10 % to 20 % * * Bio availability decreases with increasing dose.
recorded 2026-08-26 · last checked 2026-09-04
Q6
Which running trial of Aciclovir could settle lifespan?
NCT06134492 measures mortality (survival status), reading out 2026-12.
1 open trial; n 616; "Acyclovir in Ventilated Patients With Pneumonia and HSV-1 in BAL"
Show the evidence
TrialNCT06134492
"Acyclovir in Ventilated Patients With Pneumonia and HSV-1 in BAL"; n 616; "mortality (survival status)"; 2026-12
Q7
Which 28 trials of Aciclovir posted no result?
Posted no result
28 of 28 completed trials
Registrations
NCT00000985, NCT00001010, NCT00000693, NCT00000712, NCT00209352 and NCT00045292, and 22 more
Completion dates
oldest 1990-10; newest 2023-04-05
Show the evidence
Trial
NCT00000985
1990-10
NCT00001010
1990-10
NCT00000693
1992-03
NCT00000712
1994-11
NCT00209352
2004-07
NCT00045292
2004-10
14 further recorded trials
NCT00001115
2005-06
NCT00362596
2005-08
NCT00158483
2005-10
NCT00209313
2007-04
NCT00076232
2007-11
NCT00371592
2009-01
NCT02053142
2009-12
NCT00330018
2010-04
NCT00491426
2010-11
NCT00164424
2011-07
NCT00495573
2012-03
NCT02711267
2015-08
NCT02282826
2016-03
NCT02205489
2016-04
Q8
At the median, Aciclovir's trials enrolled 60 people — anything larger?
Median enrolment
60
Largest enrolment
3682
Registered trials counted
74
Q9
What do 1485 spontaneous reports say about Aciclovir — and not say?
These are reports people sent to a regulator. They do not show the medicine caused the reaction. Nobody counted how many people took the medicine and reported nothing. The same event can be reported more than once, and many reports are incomplete. News coverage, lawsuits and new warnings change how often people report. A count is not a rate and not a risk.
Aciclovir appears in spontaneous reports to regulators. Across the 10 most-reported reaction terms, 1485 reaction mentions were counted: acute kidney injury 254; renal failure acute 230; neurotoxicity 228; confusional state 159. FAERS via Open Targets · CHEMBL1200380 · 2026-06-24
Show the evidence
acute kidney injury
254
renal failure acute
230
neurotoxicity
228
confusional state
159
blood creatinine increased
138
encephalopathy
114
4 more recorded rows
renal failure
110
depressed level of consciousness
92
drug resistance
80
herpes zoster
80
recorded 2026-06-24 · last checked 2026-09-04
Q10
Which 10 reactions does Aciclovir's label not list?
2 label terms; 10 reported and unlisted; e5e99a6b-79a6-7fdb-e053-2a95a90a8563
Show the evidence
acute kidney injury
count not stated
blood creatinine increased
count not stated
confusional state
count not stated
depressed level of consciousness
count not stated
drug resistance
count not stated
encephalopathy
count not stated
4 more recorded rows
herpes zoster
count not stated
neurotoxicity
count not stated
renal failure
count not stated
renal failure acute
count not stated
recorded 2026-06-24 · last checked 2026-09-04
Where it is registered
Where it’s registered
Withdrawn in United States, 2021, for "Crystallization: customer complaints for crystallization in finished product." (openFDA drug enforcement Class I recall)
ChEMBL 37 — CC BY-SA 3.0 Unported · ClinicalTrials.gov — US Government work · Open Targets 26.06 — CC0 · mixed register set; per-register licences in docs/specs/corpus-20k-sources.md · openFDA / DailyMed — US Government work · openFDA enforcement — US Government work
✗ required summary fields resolved: 4 required field(s) not terminal: Why people use it, Best-supported result, Biggest unanswered question, Human evidence
✓ public claims reviewed: 0 reviewed claim(s); drafts are never rendered
✓ source coverage passed: 7 source rows
✓ no critical contamination: no quarantine open
✓ canonical metadata passed: slug and display name present
✓ no raw internal fields: enforced by the copy-contract test over the rendered page
This is a record of evidence. It is not medical advice, and it does not say this substance suits you. Nothing here says any substance on RNAWiki is appropriate for a child.