This page shows what was measured, who it was measured in, and what that does not settle.
What Adefovir Dipivoxil does in the body
Adefovir is a counterfeit version of one of the four DNA building blocks, wrapped in two chemical groups that let it be swallowed.
The gut and blood strip those groups off, cells add two phosphates, and the resulting molecule is picked up by the hepatitis B copying enzyme instead of the real building block. Once it is inserted, the chain cannot be extended and copying stops. The problem is that the kidney’s proximal tubule concentrates this class of molecule, and at the doses that would suppress the virus completely, it damages that tubule.
Why people take it. Long-standing hepatitis B infection.
What happened in people
Liver inflammation improved in 53 in 100 versus 25 without treatment, but only 21 in 100 fully suppressed the virus.
✓ 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
Studies examined liver samples after one year, not deaths, liver cancer or transplants.
Where it acts
Hepatocyte cytoplasm for the antiviral effect — and the proximal tubule of the kidney, which is where the dose-limiting damage happens
Kind of result
The kind of result is not recorded
Supervision
Professional supervision is normally required. A regulator classifies this substance in a way that restricts how it is supplied.
What the registries record it as
The substance registry classes this as chemical.
FDA substance registry · U6Q8Z01514 · read 2026-08-29
Its recorded molecular formula is C20H32N5O8P, weighing 501.47 g/mol.
US prescribing information · 08e07fae-3191-b6a3-c894-d3a8cc53923f · 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 117 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.
Placebo
A placebo is a dummy treatment given so the real one can be compared with it.
A picture of it, and where the picture fails
A placebo is like a blank control in an experiment.
Where that stops being true. A blank does nothing. People given a placebo often do get better.
What people get wrong. A placebo effect is read as imaginary. The improvement is measured and real.
An inactive intervention matched in appearance to the test intervention, used to control for non-specific effects.
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.
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.
Histologic improvement at week 48 in the 10 mg group compared with placebo, HBeAg-positive chronic hepatitis B
53% at 10 mg and 59% at 30 mg against 25% on placebo, both P<0.001; undetectable HBV DNA 21%, 39% and 0%
Repeated elsewhere
Replicated
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. The 30 mg arm was more effective on every virologic measure and produced a higher frequency of adverse events and renal laboratory abnormalities. The approved dose is therefore the less effective of the two the trial tested.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Oral tablet, once daily, with or without food
Interval reported. Not recorded in this summary
Written into the record, not signed off as a reviewed claim.
64% (77/121) against 33% (19/57), P<0.001; HBV DNA below 400 copies/mL in 51% (63/123) against 0% (0/61)
Repeated elsewhere
Replicated
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. Long-term follow-up of this same cohort produced the cumulative resistance figures of 3%, 11%, 19% and 30% at years two through five, which the 48-week report could not show.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Oral tablet, once daily, with or without food
Interval reported. Not recorded in this summary
Written into the record, not signed off as a reviewed claim.
17 deaths against 16 (P=0.88); mean log10 HIV RNA change +0.09 against -0.03 at 6 months (P=0.22); proximal renal tubular dysfunction 17% against 0.4% at 12 months (P<0.0001)
Repeated elsewhere
Failed to Replicate
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. Median time to resolution of renal tubular dysfunction was 15 weeks and 16% of affected patients had not fully resolved 41 weeks after onset. The authors concluded the study did not support use of adefovir in advanced HIV disease.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Oral tablet, once daily, with or without food
Interval reported. Not recorded in this summary
Written into the record, not signed off as a reviewed claim.
RNAWiki holds 3 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
Adefovir Dipivoxil
What a person takes: Oral tablet, once daily, with or without food.
The measurement behind this step
One 10 mg tablet once daily, taken indefinitely. The dosing interval must be lengthened as creatinine clearance falls, and renal function is monitored throughout because the dose sits close to the threshold at which this chemical class damages the proximal tubule.
Getting in
One 10 mg tablet a day — a dose set by the kidney
The approved dose is a twelfth of what was tested in HIV. The trial that approved it also tested triple this dose, which worked better and caused more kidney abnormalities.
╌╌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
Adefovir dipivoxil 10 mg once daily. In study 437 the 30 mg arm reached 39% undetectable HBV DNA against 21% at 10 mg, with a higher frequency of adverse events and renal laboratory abnormalities. Dose interval must be extended as creatinine clearance falls.
The molecule that works cannot be absorbed from the gut, so it is given wrapped in two ester groups that are stripped off after absorption.
╌╌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
Adefovir dipivoxil is the bis(pivaloyloxymethyl) prodrug of adefovir, an acyclic nucleotide phosphonate whose permanent negative charge prevents oral absorption. Each ester cleaved releases a molecule of pivalic acid, which depletes carnitine — the reason the HIV trials at 120 mg co-administered L-carnitine.
Phosphorylated twice and inserted into the growing viral DNA
Cells add two phosphates. The result looks enough like a real DNA building block that the viral copying enzyme picks it up.
╌╌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
Adefovir is converted to adefovir diphosphate, which competes with deoxyadenosine triphosphate at the HBV reverse transcriptase. Because the molecule is acyclic and lacks a 3-hydroxyl, incorporation terminates the chain.
Viral DNA falls sharply but reaches undetectable in only a minority: one in five HBeAg-positive patients and half of HBeAg-negative ones after a year.
──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
Median HBV DNA reduction 3.52 log copies/mL at 10 mg, with 21% below 400 copies/mL in HBeAg-positive and 51% in HBeAg-negative patients at week 48. For comparison, entecavir reached 67% and 90% in the same populations.
The endpoint the trials were built on was what the liver looked like under a microscope, and on that measure it clearly beat placebo.
╌╌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
Histologic improvement in 53% against 25% on placebo in HBeAg-positive disease and 64% against 33% in HBeAg-negative disease, both at week 48 and both P<0.001. ALT normalised in 48% and 72%.
Because the dose is capped by kidney safety, there is very little margin. By five years, three in ten patients had resistant virus — twenty-five times the rate of the drug that replaced it.
╌╌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
Cumulative resistance probability 0%, 3%, 11%, 19% and 30% at weeks 48 to 240, driven by rtN236T and rtA181T/V, which confer only 1.3- to 14-fold reductions in susceptibility. Small fold-changes suffice when there is no exposure headroom.
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.
Very few people now. It has been superseded by entecavir and tenofovir, which suppress the virus far more completely and select resistance far less often. Anyone taking it needs renal monitoring, and anyone stopping it needs hepatic monitoring.
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: “Pediatric patients 12 to less than 18 years : The safety, efficacy, and pharmacokinetics of adefovir dipivoxil in pediatric patients (aged 12 to less than 18 years) were evaluated in a double-blind, randomized, placebo-controlled study (GS-US-103-518, Study 518) in 83 pediatric patients with chronic hepatitis B and compensated liver disease.”
US prescribing information · 08e07fae-3191-b6a3-c894-d3a8cc53923f · read 2026-08-30
On older people, the label states: “Clinical studies of adefovir dipivoxil did not include sufficient numbers of patients aged 65 and over to determine whether they respond differently from younger patients.”
US prescribing information · 08e07fae-3191-b6a3-c894-d3a8cc53923f · read 2026-08-30
On people who are pregnant, the label states: “Adefovir disoproxil (ADV) use during pregnancy has been evaluated in a limited number of individuals reported to the APR and the number of exposures to adefovir is insufficient to make a risk assessment compared to a reference population.”
US prescribing information · 08e07fae-3191-b6a3-c894-d3a8cc53923f · read 2026-08-30
On people who are breastfeeding, the label states: “Risk Summary It is not known whether adefovir is present in human breast milk, affects human milk production, or has effects on the breastfed infant.”
US prescribing information · 08e07fae-3191-b6a3-c894-d3a8cc53923f · read 2026-08-30
Where the result stopped carrying
Rejected in HIV: no survival, CD4 or viral load benefit at 120 mg, with 17% proximal renal tubular dysfunction
Kidney toxicity capped the hepatitis B dose below the dose the same trial showed to be more effective
Undetectable HBV DNA in only 21% of HBeAg-positive patients at a year, against 67% for entecavir
Cumulative resistance of 30% at five years, twenty-five times the entecavir figure measured the same way
Four boxed warnings, including nephrotoxicity and severe hepatitis flares on discontinuation
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.
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 (11)
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.
There was nothing to correct
Where a level is already normal, topping it up may change nothing. 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
Prescription only
❝ 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 tablet, once daily, with or without food
✎ 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
Professional supervision is normally required. A regulator classifies this substance in a way that restricts how it is supplied.
❝ Quoted from a source
Where this came from
Copied from a source RNAWiki stored, with the source named.
Suppression classes recorded: S6.
No source is stored against this line.
What is in the pack
One 10 mg tablet once daily, taken indefinitely.
✎ 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. The rest of the recorded wording: The dosing interval must be lengthened as creatinine clearance falls, and renal function is monitored throughout because the dose sits close to the threshold at which this chemical class damages the proximal tubule.
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
Four boxed warnings: severe acute exacerbations of hepatitis after discontinuation, requiring hepatic monitoring for at least several months; nephrotoxicity with chronic administration in patients at risk of or with underlying renal dysfunction; emergence of HIV resistance if given to someone with unrecognised or untreated HIV; and lactic acidosis with severe hepatomegaly and steatosis as a nucleoside analogue class effect. At the approved 10 mg dose the trial safety profile was similar to placebo over 48 weeks; the renal signal is a long-term and dose-related one, established at 120 mg in the HIV programme where 17% developed proximal renal tubular dysfunction within a year.
Nobody counted how many people took this and were fine, so this cannot be turned into a rate.
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 tablet, once daily, with or without food
✎ 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
A recorded note compares this form with the others that are sold. It is kept below, word for word.
§ A fixed RNAWiki sentence
Where this came from
Wording RNAWiki always uses, not a finding about this substance.
The recorded note, unchanged: The dosing interval must be lengthened as creatinine clearance falls, and renal function is monitored throughout because the dose sits close to the threshold at which this chemical class damages the proximal tubule.
No source is stored against this line.
What is recorded as being sold
3 products list this as an active ingredient in the United States drug directory. 3 of them contain it and nothing else.
FDA National Drug Code directory · 42794-003 · read 2026-08-29
They are sold as powder and tablet, taken oral.
FDA National Drug Code directory · 42794-003 · read 2026-08-29
The regulator's established pharmacologic class for it is hepatitis b virus nucleoside analog reverse transcriptase inhibitor [epc], nucleoside analog [ext] and nucleoside reverse transcriptase inhibitors [moa].
FDA National Drug Code directory · 42794-003 · read 2026-08-29
2 published labels name it as an active ingredient. 2 of them describe this substance alone, which is where its own label text on this page comes from.
US prescribing information · 08e07fae-3191-b6a3-c894-d3a8cc53923f · read 2026-08-29
Those labels are classed as human prescription drug.
US prescribing information · 08e07fae-3191-b6a3-c894-d3a8cc53923f · read 2026-08-29
Adefovir dipivoxil is oral at 3 DOSAGE FORMS AND STRENGTHS Adefovir Dipivoxil Tablets are white to off-white, round, flat-faced bevelled edge tablets, engraved “APO” on one side, “A10” on the other side., recorded as fda label in effect 2025-07-22 in the United States.
US prescribing information · 08e07fae-3191-b6a3-c894-d3a8cc53923f · read 2026-08-30
Recorded price in US: 21.73128 USD per one unit as the pricing file counts it — a tablet, capsule, patch or single item, across 2 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.
Self-experiment planning is not offered for a prescription or clinician-supervised medicine. The questions below are for a clinician or pharmacist.
Questions worth asking
Which of the trials of Adefovir Dipivoxil 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 adefovir reduces hepatocellular carcinoma or decompensation; the randomised outcome evidence in hepatitis B belongs to lamivudine
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 histologic improvement at 48 weeks predicts the five-year course, when 30% of the same cohort had developed resistance by then
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 10 mg is the effective dose rather than the tolerable one — the trial’s own 30 mg arm suppressed nearly twice as many patients
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 modest resistance fold-change implies a modest clinical problem; with no exposure headroom, fourfold was enough
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 Adefovir Dipivoxil 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.
It failed in HIV first: no benefit, and renal tubular damage in 17%
In plain words
Before it was a hepatitis B drug, adefovir was tested for HIV at twelve times the dose. In 505 patients with advanced disease it produced no survival benefit, no CD4 benefit and no measurable fall in HIV levels — and damaged the kidney tubules of 17% of them within a year.
What was measured
Proximal renal tubular dysfunction 17% against 0.4% at 12 months at the 120 mg HIV dose, with no virologic or immunologic benefit
Effect estimate
No reviewed effect estimate exists for this record.
Limits
This entry records a failure.
From the source
A randomised, double-blind, placebo-controlled trial assigned 253 patients with advanced HIV to adefovir dipivoxil 120 mg daily and 252 to placebo, added to background antiretroviral therapy. Deaths were 17 and 16 (P=0.88) and cytomegalovirus disease 4 and 8 (P=0.25). Mean change in log10 plasma HIV RNA was +0.09 with adefovir against -0.03 with placebo at 6 months (P=0.22) and +0.06 against -0.02 at 12 months (P=0.87). CD4 changes did not differ. Cumulative proximal renal tubular dysfunction at 12 months was 17% with adefovir against 0.4% with placebo (P<0.0001, log rank). Median time to resolution was 15 weeks and 16% of affected patients had not fully resolved 41 weeks after onset. The authors concluded the study did not support the use of adefovir for advanced HIV disease. A separate 442-patient trial at the same dose found a 0.4 log10 HIV RNA decline with no CD4 change, alongside elevated hepatic enzymes, gastrointestinal complaints and weight loss — and every patient in it received supplementary L-carnitine, because the prodrug releases pivalic acid.
Written into the record, not signed off as a reviewed claim
At 10 mg in hepatitis B it beat placebo on liver biopsy, 53% against 25%
In plain words
Five hundred and fifteen patients were randomly assigned adefovir or a dummy tablet for a year. Just over half the treated patients had measurably less inflammation on biopsy, against a quarter on placebo.
What was measured
Histologic improvement at week 48: 53% at 10 mg and 59% at 30 mg against 25% on placebo
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
Study GS-98-437 randomised 515 HBeAg-positive patients to adefovir dipivoxil 10 mg (n=172), 30 mg (n=173) or placebo (n=170) daily for 48 weeks, with histologic improvement in the 10 mg group against placebo as the primary endpoint. Histologic improvement occurred in 53%, 59% and 25% (both P<0.001). Median HBV DNA reduction was 3.52, 4.76 and 0.55 log copies/mL. Undetectable HBV DNA below 400 copies/mL was 21%, 39% and 0%. ALT normalisation was 48%, 55% and 16%. HBeAg seroconversion was 12%, 14% and 6% (P=0.049 and P=0.01). No adefovir resistance mutations were identified at week 48. A placebo-controlled trial with a liver biopsy endpoint is a stronger design than most hepatitis B evidence, and it is worth crediting.
Written into the record, not signed off as a reviewed claim
The same trial shows exactly what the higher dose bought, and what it cost
In plain words
The trial tested two doses. The triple dose suppressed nearly twice as many patients’ virus below detection — and produced more side effects and more kidney abnormalities. The lower dose was the one approved.
What was measured
Undetectable HBV DNA 39% at 30 mg against 21% at 10 mg, with more adverse events and renal laboratory abnormalities at 30 mg
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
Within study 437, the 30 mg arm reached 39% undetectable HBV DNA against 21% at 10 mg, a median 4.76 against 3.52 log reduction, and 59% against 53% histologic improvement. The authors record that the safety profile of the 10 mg dose was similar to placebo, whereas there was a higher frequency of adverse events and renal laboratory abnormalities at 30 mg, and they conclude that the 10 mg dose has a favourable risk-benefit profile for long-term treatment. This is unusually explicit: a registrational trial that measured its own dose-response for both efficacy and toxicity and published the trade-off rather than presenting only the chosen dose. It also explains everything downstream — the incomplete suppression and the resistance rate are consequences of a dose set by the kidney rather than by the virus.
Written into the record, not signed off as a reviewed claim
Replicated in HBeAg-negative disease, also against placebo
In plain words
A second placebo-controlled trial in a different form of hepatitis B found the same pattern: 64% improved on biopsy against 33%, and half the treated patients had undetectable virus against none on placebo.
What was measured
Histologic improvement 64% against 33% and undetectable HBV DNA 51% against 0% at week 48
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
Study GS-98-438 randomised 185 HBeAg-negative patients 2:1 to adefovir dipivoxil 10 mg or placebo for 48 weeks, double-blind, with histologic improvement as the primary endpoint. Improvement occurred in 64% (77/121 evaluable) against 33% (19/57), P<0.001. HBV DNA fell below 400 copies/mL in 51% (63/123) against 0% (0/61), P<0.001, and ALT normalised in 72% (84/116) against 29%. The safety profile was similar to placebo and no adefovir resistance mutations were identified at 48 weeks. Placed beside the entecavir programme, which reached 90% undetectable in the same population, the gap in antiviral potency between the two drugs is visible in the same units.
Written into the record, not signed off as a reviewed claim
Cumulative resistance of 30% at five years, against 1.2% for entecavir
In plain words
By the fifth year of continuous treatment, three in ten patients had developed resistance. The drug that replaced it reaches just over one in a hundred over the same period, measured the same way.
What was measured
Cumulative resistance probability 0%, 3%, 11%, 19%, 30% at weeks 48 to 240, against 0.2% to 1.2% for entecavir
Effect estimate
No reviewed effect estimate exists for this record.
Limits
This entry records a failure.
From the source
In HBeAg-negative nucleoside-naive patients in study GS-98-438, isolates from 30 patients carried adefovir resistance-associated substitutions with a cumulative probability of 0%, 3%, 11%, 19% and 30% at weeks 48, 96, 144, 192 and 240. Twenty-two of those 30 had confirmed virologic failure and eight had substitutions without failure. In HBeAg-positive patients continuing long term after a median 235 weeks, 16 of 38 (42%) developed resistance substitutions in the setting of virologic failure. The substitutions are rtN236T and rtA181T/V, conferring only 4- to 14-fold, 1.3- to 1.9-fold and 2.5- to 4.2-fold reductions in susceptibility respectively. The entecavir label, using the same cumulative-probability method over identical weeks, reports 0.2%, 0.5%, 1.2%, 1.2% and 1.2%. The two figures are directly comparable and differ by a factor of twenty-five at five years.
Source
Adefovir dipivoxil United States prescribing information, Microbiology, resistance (openFDA); entecavir comparison from BARACLUDE United States prescribing information, Clinical Pharmacology
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
Four boxed warnings, one of them about the kidney the drug was already known to damage
In plain words
The label carries four boxed warnings: hepatitis flares on stopping, kidney toxicity with long-term use, HIV resistance if HIV is present but untreated, and a rare metabolic complication shared by the whole drug class.
What was measured
Not recorded
Effect estimate
No reviewed effect estimate exists for this record.
Limits
This entry records a failure.
From the source
The boxed warning covers severe acute exacerbations of hepatitis after discontinuation, requiring hepatic monitoring for at least several months; nephrotoxicity from chronic administration in patients at risk of or with underlying renal dysfunction, requiring close renal monitoring and dose adjustment; emergence of HIV resistance in patients with unrecognised or untreated HIV infection given a hepatitis B therapy with anti-HIV activity; and lactic acidosis with severe hepatomegaly and steatosis, including fatal cases, as a nucleoside analogue class effect. The nephrotoxicity warning is the one worth reading against the history: the renal signal was established in the HIV programme years before this indication existed, and the hepatitis B dose was chosen to stay under it rather than to eliminate it.
Source
Adefovir dipivoxil United States prescribing information, boxed warning and Warnings and Precautions 5.1 to 5.4 (openFDA drug label endpoint)
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
A drug rejected at one dose, approved at a twelfth of it, then superseded by its own relative
In plain words
Adefovir failed in HIV at 120 mg, was approved for hepatitis B at 10 mg, and was then displaced by tenofovir — a chemically similar nucleotide that could safely be given at 300 mg because its delivery chemistry was better.
What was measured
Not recorded
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
The three facts in sequence tell one story about therapeutic index rather than three separate stories. At 120 mg adefovir produced 17% proximal renal tubular dysfunction with no HIV benefit. At 10 mg it produced 21% and 51% undetectable HBV DNA in the two hepatitis B populations — real efficacy, incompletely delivered, because the dose was capped by the kidney. Tenofovir disoproxil fumarate, the same acyclic nucleotide phosphonate class with a different oral prodrug, is given at 300 mg and suppresses hepatitis B far more completely with no clinically significant resistance pathway identified. Tenofovir alafenamide went further, delivering the same active molecule at roughly a tenth of the plasma exposure. Adefovir is not a failed molecule; it is a molecule whose delivery chemistry was solved by its successors, and it retains a niche only where lamivudine resistance rules out entecavir.
Written into the record, not signed off as a reviewed claim
The endpoint was a biopsy score, and the outcome evidence belongs to lamivudine
In plain words
Both approval trials measured what the liver looked like under a microscope after a year. Neither counted deaths, cancers or transplants — and the only hepatitis B trial that did tested a different drug.
What was measured
That adefovir reduces hepatocellular carcinoma or decompensation — demonstrated by randomisation for lamivudine, extrapolated to adefovir from a biopsy score and a partial viral suppression
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
Studies 437 and 438 used histologic improvement at week 48 as the primary endpoint, with viral load, ALT and seroconversion as secondary measures. The single randomised placebo-controlled trial in hepatitis B that measured clinical outcomes — hepatic decompensation, hepatocellular carcinoma, death — randomised 651 patients with cirrhosis or advanced fibrosis to lamivudine or placebo and found progression in 7.8% against 17.7% and cancer in 3.9% against 7.4%. Adefovir has never been randomised against placebo for those endpoints, and after that lamivudine result a placebo arm in hepatitis B became indefensible. The inference that better histology and lower viral load on adefovir translate into fewer cancers is reasonable and untested by randomisation — and it is a weaker inference here than for entecavir, because adefovir suppresses so much less completely.
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What is not here
7 questions this page could not answer
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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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The full record, for auditing
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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 nucleotide analogue that failed in HIV at 120 mg — no virologic or immunologic benefit against placebo in 505 patients with advanced disease, and proximal renal tubular dysfunction in 17% against 0.4% — and was then approved for hepatitis B at 10 mg, where it produced histologic improvement in 53% against 25% on placebo but suppressed HBV DNA below detection in only 21% of patients and reached a cumulative 30% resistance by five years.
Recorded evidence blocks (11)
Q2
On the Adefovir Dipivoxil label: indicated for what?
"Adefovir dipivoxil tablets are indicated for the treatment of chronic hepatitis B in patients 12 years of age and older with evidence of active viral replication and either evidence of persistent elevations in serum aminotransferases (ALT or AST) or histologically active disease. This indication is based on…": indications and usage on Adefovir Dipivoxil's label. DailyMed label · 08e07fae-3191-b6a3-c894-d3a8cc53923f · 2025-07-22
Q3
64 registered trials of Adefovir Dipivoxil — at which phases?
Registered studies posting no result
49 of 64
64 registered studies of Adefovir Dipivoxil: 20 phase4, 15 phase3, 14 phase2, 7 na, 7 phase1, 3 na or unstated. CLINICALTRIALS_SNAPSHOT · 2026-09-01
190 with a PubMed record
Show the evidence
phase4
20
phase3
15
phase2
14
na
7
phase1
7
na or unstated
3
5 more recorded rows
completed
48
unknown
8
withdrawn
4
terminated
3
approved for marketing
1
recorded 2026-09-01 · last checked 2026-09-04
Q4
6 of Adefovir Dipivoxil's trials stopped: accrual/recruitment, funding/business, other?
7.48 ± 1.65 hours; Plasma adefovir concentrations declined in a biexponential manner with a terminal elimination half-life of 7.48 ± 1.65 hours.
bioavailabilitypharmacokinetics
59 %; Based on a cross study comparison, the approximate oral bioavailability of adefovir from adefovir dipivoxil is 59%.
metabolismpharmacokinetics
Metabolism and Elimination Following oral administration, adefovir dipivoxil is rapidly converted to adefovir.
recorded 2025-07-22 · last checked 2026-09-04
Q7
Which 21 trials of Adefovir Dipivoxil posted no result?
Posted no result
21 of 21 completed trials
Registrations
NCT00000892, NCT00001082, NCT00000912, NCT00001087, NCT00000885 and NCT00645294, and 15 more
Completion dates
oldest 1999-08; newest 2019-10
Show the evidence
Trial
NCT00000892
1999-08
NCT00001082
1999-08
NCT00000912
2000-05
NCT00001087
2000-07
NCT00000885
2003-06
NCT00645294
2003-08
14 further recorded trials
NCT00023153
2004-10
NCT00033163
2005-05
NCT00644761
2005-05
NCT00158717
2006-04
NCT00115245
2006-08
NCT00230477
2007-08
NCT00307242
2009-02-05
NCT02598063
2009-04
NCT00640588
2009-12
NCT01353742
2011-04-12
NCT00661076
2011-05
NCT00672867
2014-09
NCT01732367
2016-04
NCT02743260
2017-12
Q8
At the median, Adefovir Dipivoxil's trials enrolled 100 people — anything larger?
Median enrolment
100
Largest enrolment
4393
Registered trials counted
61
Q9
What do 2347 spontaneous reports say about Adefovir Dipivoxil — 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.
Adefovir Dipivoxil appears in spontaneous reports to regulators. Across the 10 most-reported reaction terms, 2347 reaction mentions were counted: osteomalacia 412; drug resistance 357; hypophosphataemia 345; fanconi syndrome acquired 244. FAERS via Open Targets · CHEMBL922 · 2026-06-24
Show the evidence
osteomalacia
412
drug resistance
357
hypophosphataemia
345
fanconi syndrome acquired
244
osteoporosis
217
bone pain
186
4 more recorded rows
arthralgia
172
renal impairment
143
viral mutation identified
137
blood phosphorus decreased
134
recorded 2026-06-24 · last checked 2026-09-04
Q10
Which 10 reactions does Adefovir Dipivoxil's label not list?
At concentrations substantially higher (greater than 4000-fold) than those observed in vivo , adefovir did not inhibit any of the common human CYP450 enzymes, CYP1A2, CYP2C9, CYP2C19, CYP2D6, and CYP3A4.
clinical_pharmacology
At concentrations substantially higher (greater than 4000-fold) than those observed in vivo , adefovir did not inhibit any of the common human CYP450 enzymes, CYP1A2, CYP2C9, CYP2C19, CYP2D6, and CYP3A4.
ChEMBL 37 — CC BY-SA 3.0 Unported · ChEMBL ATC CC BY-SA · ClinicalTrials.gov — US Government work · EMA medicine register · Open Targets 26.06 — CC0 · mixed register set; per-register licences in docs/specs/corpus-20k-sources.md · openFDA / DailyMed — US Government work
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