This page shows what was measured, who it was measured in, and what that does not settle.
What Tenofovir Disoproxil does in the body
HIV-1 infection, HIV prevention, and chronic hepatitis B
The active drug, tenofovir, is an impostor version of one of the four chemical letters that DNA is built from. The copying enzymes of HIV and of hepatitis B both pick it up and stitch it into the growing chain, and then discover there is nowhere to attach the next letter, so the copy stops dead. Tenofovir on its own cannot get into a cell, so it is given inside a wrapper that dissolves in the bloodstream within seconds and releases it.
What happened in people
84% against 73% below 400 copies per millilitre at week 48 in Study 934 (95% CI for the difference 4 to 19, p=0.002), with discontinuation for adverse events of 4% against 9%
✎ 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 recorded finding that sits closest to something a person would notice. Written into the record, not signed off, and it carries no population or interval.
A first-line hepatitis B treatment with the only paired-biopsy evidence of cirrhosis regression in the class
Where it acts
Cytoplasm of CD4-positive T cells and hepatocytes, with the proximal renal tubule as the site of the characteristic toxicity
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 · F4YU4LON7I · read 2026-08-29
Its recorded molecular formula is C19H30N5O10P•C4H4O4, weighing 635.52.
US prescribing information · 67e0e1b7-6a45-4d63-b569-00826832c25a · read 2026-08-30
Where each sentence above came from
The recorded explanation names an amount, so it does not open this page. The page opens with what it is taken for instead, and the recorded explanation follows below.
Shown as the opening line on this page.
A limit recorded against this substance. Not signed off as a reviewed claim.
The four opening statements run to 126 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.
Proportion with HIV-1 RNA below 400 copies per millilitre at week 48 against stavudine, intention to treat
✗ The study did not show it
Who was studied
Study 903
How many people
602
Study design
Phase 3, randomised, double-blind, equivalence, 48-week primary with 144-week follow-up
Compared against
Not recorded for this study
Kind of result
A number that stands in for health
What was found
80% versus 84%, 95% CI -10.4% to 1.5%, exceeding the predefined -10% equivalence limit; equivalence met in the secondary analysis at 50 copies per millilitre
Repeated elsewhere
Partially 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. The result that mattered was metabolic and was a secondary endpoint: lipodystrophy in 3% against 19%, and a triglyceride rise of 1 mg/dL against 134 mg/dL at week 144.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Oral tablet and oral powder, as a single agent and in fixed-dose combinations
Interval reported. 95% CI -10
Written into the record, not signed off as a reviewed claim.
Histological improvement and fibrosis regression on paired liver biopsy at week 240
✓ The study showed what it set out to show
Who was studied
Hepatitis B open-label extension, week 240 biopsy
How many people
348
Study design
Open-label seven-year extension with prespecified repeat liver biopsy, no comparator
Compared against
Not recorded for this study
Kind of result
A number that stands in for health
What was found
87% histological improvement and 51% fibrosis regression, p<0.0001; 71 of 96 baseline cirrhotics no longer cirrhotic
Repeated elsewhere
Partially 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. Only 348 of 641 randomised patients (54%) had biopsies at both time points, and the extension had no control arm, so the comparison is with baseline rather than with untreated disease.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Oral tablet and oral powder, as a single agent and in fixed-dose combinations
Interval reported. Not recorded in this summary
Written into the record, not signed off as a reviewed claim.
Incident HIV-1 infection in HIV-negative African women
✗ The study did not show it
Who was studied
FEM-PrEP (NCT00625404)
How many people
2120
Study design
Phase 3, randomised, double-blind, placebo-controlled, stopped early for futility
Compared against
A dummy treatment
Kind of result
A number that stands in for health
What was found
Hazard ratio 0.94 (95% CI 0.59 to 1.52), p=0.81
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. Fewer than 40% of uninfected women in the active group had evidence of recent pill use at visits matched to the infection window, which is a measurement the trial made and the headline result did not carry.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Oral tablet and oral powder, as a single agent and in fixed-dose combinations
Interval reported. 95% CI 0
Written into the record, not signed off as a reviewed claim.
Incident HIV-1 infection in African women, modified intention to treat
✗ The study did not show it
Who was studied
VOICE (NCT00705679)
How many people
5029
Study design
Phase 2B, randomised, placebo-controlled, four arms, two oral and one gel
Compared against
A dummy treatment
Kind of result
A number that stands in for health
What was found
Effectiveness -49.0% for tenofovir (hazard ratio 1.49, 95% CI 0.97 to 2.29), -4.4% for tenofovir-emtricitabine and 14.5% for gel
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. Tenofovir was detected in 30%, 29% and 25% of sampled plasma across the three active arms, and detection was negatively associated with the characteristics that predicted acquisition.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Oral tablet and oral powder, as a single agent and in fixed-dose combinations
Interval reported. 95% CI 0
Written into the record, not signed off as a reviewed claim.
RNAWiki holds 8 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
Tenofovir Disoproxil
What a person takes: Oral tablet and oral powder, as a single agent and in fixed-dose combinations.
The measurement behind this step
Taken once daily. Bioavailability is around 25% fasted and rises with a high-fat meal. Ritonavir and cobicistat raise tenofovir exposure substantially, which is why the renal risk concentrates in boosted regimens. Renal dose adjustment is required below a creatinine clearance of 50 mL/min, and it is not recommended below 30 mL/min in adults.
Getting in
Swallowed as a wrapper designed to fall apart immediately
The tablet contains the active drug sealed behind two chemical groups that are stripped off by enzymes in the blood within seconds of absorption. That is deliberate: it is what lets an otherwise impermeable molecule be taken by mouth.
──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
Tenofovir disoproxil fumarate carries two isopropyloxycarbonyloxymethyl esters on the phosphonate. Plasma and intestinal esterases cleave them almost immediately, releasing free tenofovir into the circulation. Oral bioavailability of tenofovir from the prodrug is roughly 25% in the fasted state and higher with a high-fat meal. The consequence of releasing free drug into plasma is the whole subject of the tenofovir alafenamide record: circulating tenofovir reaches the kidney and the skeleton.
Free drug is pulled into cells, and into the kidney tubule
Tenofovir gets into target cells slowly. It also gets pulled into the cells lining the kidney tubule by transporters that were not built with this drug in mind, which is where the known kidney side effect comes from.
╌╌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
Tenofovir is a substrate of the basolateral organic anion transporters OAT1 and OAT3, which concentrate it in proximal tubular epithelium, and is exported by MRP4 on the apical side. When uptake outpaces efflux the drug accumulates and mitochondrial DNA polymerase gamma is inhibited, which is the mechanistic account of the tubulopathy and of Fanconi syndrome. Boosting agents such as ritonavir and cobicistat raise tenofovir exposure and are the co-factor in most reported cases.
Two phosphates turn it into a counterfeit DNA letter
Inside the cell, ordinary cellular enzymes attach two phosphate groups. The finished molecule looks enough like one of the four building blocks of DNA that the viral copying machine cannot tell the difference.
╌╌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
Adenylate kinase converts tenofovir to the monophosphate and nucleoside diphosphate kinase to tenofovir diphosphate, the active species and an analogue of deoxyadenosine triphosphate. The intracellular half-life of tenofovir diphosphate in PBMCs runs to days, which supports once-daily dosing and is the basis of the dried blood spot assay used to measure adherence retrospectively in the prevention trials.
It is stitched into the chain, and the chain ends there
The viral enzyme inserts it into the DNA it is building. There is no attachment point for the next letter, so the copy stops at that spot and cannot be finished.
──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
Tenofovir diphosphate competes with dATP for the polymerase active site and is incorporated, after which the absence of a 3-prime hydroxyl on the acyclic linker enforces obligate chain termination. The same chemistry works on HIV-1 reverse transcriptase and on the reverse transcriptase domain of the hepatitis B polymerase. The signature HIV resistance mutation is K65R, which discriminates against the analogue at incorporation and costs the virus replicative fitness; it emerged in 8 of 299 patients over 144 weeks in Study 903 and in none in Study 934.
Virus falls, and in hepatitis B the liver scar reverses
HIV drops below detection and stays there while the drug is taken. In hepatitis B, sustained suppression does something no viral load number can show on its own: repeat biopsies after five years found scarring reversed in most patients who started with cirrhosis.
──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
In HIV the effect is suppression, not clearance, because integrated provirus is untouched. In hepatitis B, five years of open-label treatment with a prespecified repeat biopsy at week 240 produced histological improvement in 304 of 348 patients (87%) and loss of the cirrhosis threshold in 71 of 96 who met it at baseline (74%). Covalently closed circular DNA persists in the hepatocyte nucleus, so hepatitis B is suppressed rather than cured too, which is why stopping causes the severe flare that carries the boxed warning.
No suggested links are held for this record, so nothing is hidden from this path.
What we know
The record describes 5 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 taking generic tenofovir-lamivudine-dolutegravir, the WHO first-line regimen; people taking emtricitabine-tenofovir disoproxil for pre-exposure prophylaxis; and adults and children with chronic hepatitis B.
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: “Five additional subjects over the age of 12 were enrolled and randomized (tenofovir disoproxil fumarate tablets N=4, original regimen N=1) but are not included in the efficacy analysis.”
US prescribing information · 67e0e1b7-6a45-4d63-b569-00826832c25a · read 2026-08-30
On older people, the label states: “Clinical trials of tenofovir disoproxil fumarate tablets did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects.”
US prescribing information · 67e0e1b7-6a45-4d63-b569-00826832c25a · read 2026-08-30
On people who are pregnant, the label states: “Category B There are no adequate and well-controlled studies in pregnant women.”
US prescribing information · 67e0e1b7-6a45-4d63-b569-00826832c25a · read 2026-08-30
On people who are breastfeeding, the label states: “The Centers for Disease Control and Prevention recommend that HIV-1 infected mothers not breastfeed their infants to avoid risking postnatal transmission of HIV-1.”
US prescribing information · 67e0e1b7-6a45-4d63-b569-00826832c25a · read 2026-08-30
Where the result stopped carrying
Study 903 missed its primary equivalence margin at week 48, with a confidence interval reaching -10.4% against a -10% limit
FEM-PrEP was stopped early for lack of efficacy after a hazard ratio of 0.94, and VOICE reported a point estimate of -49.0% effectiveness for oral tenofovir
The initial reading of those two trials, that oral prevention does not protect African women, was retired once the drug concentration data from inside them were analysed
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 and oral powder, as a single agent and in fixed-dose combinations
✎ 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
Taken once daily. Bioavailability is around 25% fasted and rises with a high-fat meal. Ritonavir and cobicistat raise tenofovir exposure substantially, which is why the renal risk concentrates in boosted regimens. Renal dose adjustment is required below a creatinine clearance of 50 mL/min, and it is not recommended below 30 mL/min in adults.
✎ 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
Severe acute exacerbation of hepatitis B on discontinuation is a boxed warning; hepatic function must be monitored for months after stopping in anyone with hepatitis B. Renal impairment including acute renal failure, proximal tubulopathy and Fanconi syndrome is labelled, with the risk concentrated in patients with pre-existing renal disease and those on boosted regimens. Bone mineral density falls in the first six months and then stabilises. Lactic acidosis and severe hepatomegaly with steatosis are labelled class effects. Relative to the successor prodrug it lowers LDL cholesterol and suppresses weight gain, which are effects rather than absences of effect and complicate every comparison between the two.
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 and oral powder, as a single agent and in fixed-dose combinations
✎ 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
Bioavailability is around 25% fasted and rises with a high-fat meal. Ritonavir and cobicistat raise tenofovir exposure substantially, which is why the renal risk concentrates in boosted regimens. Renal dose adjustment is required below a creatinine clearance of 50 mL/min, and it is not recommended below 30 mL/min in adults.
✎ 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
135 products list this as an active ingredient in the United States drug directory. 53 of them contain it and nothing else.
FDA National Drug Code directory · 50683-0289 · read 2026-08-29
They are sold as powder, tablet, tablet, coated and tablet, film coated, taken oral.
FDA National Drug Code directory · 50683-0289 · read 2026-08-29
The regulator's established pharmacologic class for it is hepatitis b virus nucleoside analog reverse transcriptase inhibitor [epc], human immunodeficiency virus nucleoside analog reverse transcriptase inhibitor [epc] and nucleoside reverse transcriptase inhibitors [moa].
FDA National Drug Code directory · 50683-0289 · read 2026-08-29
69 published labels name it as an active ingredient. 18 of them describe this substance alone, which is where its own label text on this page comes from.
US prescribing information · 54e82b13-a037-49ed-b4b3-030b37c0ecdd · read 2026-08-29
Those labels are classed as human prescription drug.
US prescribing information · 54e82b13-a037-49ed-b4b3-030b37c0ecdd · read 2026-08-29
Tenofovir Disoproxil Fumarate is oral at 3 DOSAGE FORMS & STRENGTHS Tenofovir disoproxil fumarate is available as tablets., recorded as fda label in effect 2024-08-05 in the United States.
US prescribing information · 67e0e1b7-6a45-4d63-b569-00826832c25a · read 2026-08-30
Recorded price in US: 0.31102 USD per one unit as the pricing file counts it — a tablet, capsule, patch or single item, across 12 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 Tenofovir Disoproxil 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 FEM-PrEP and VOICE would have shown efficacy at high adherence — supported by measured drug concentrations, but a counterfactual no randomised comparison in either trial tested
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 small, non-progressive eGFR and bone density changes measured in HIV-negative prevention cohorts describe the risk after decades of treatment exposure
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 Study 903 demonstrated equivalence to stavudine at its primary endpoint, which its own confidence interval says it did not
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 Tenofovir Disoproxil 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.
Study 934: 84% against 73%, and superior rather than merely non-inferior
In plain words
Against the zidovudine-based regimen that was standard at the time, tenofovir with emtricitabine and efavirenz suppressed more people, raised CD4 counts more, and drove fewer people off treatment with side effects. It was designed to prove it was no worse and it proved it was better.
What was measured
Proportion with HIV-1 RNA below 400 copies per millilitre at week 48 without baseline efavirenz resistance
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
Study 934 (NCT00112047) was an open-label non-inferiority trial in 517 treatment-naive patients randomised to tenofovir disoproxil fumarate with emtricitabine and efavirenz once daily, or to fixed-dose zidovudine-lamivudine twice daily with efavirenz. At week 48, 84% against 73% had HIV-1 RNA below 400 copies per millilitre (95% CI for the difference 4 to 19, p=0.002), crossing from non-inferiority into superiority. Below 50 copies per millilitre the figures were 80% against 70% (95% CI 2 to 17, p=0.02). Mean CD4 increase was 190 against 158 cells per cubic millimetre (95% CI 9 to 55, p=0.002). Adverse events causing discontinuation occurred in 4% against 9% (p=0.02). The K65R mutation, the signature tenofovir resistance change, developed in no patient in either arm.
Written into the record, not signed off as a reviewed claim
Study 903 missed its own primary equivalence margin, and was rescued by a secondary
In plain words
The three-year trial against stavudine set an equivalence limit of ten percentage points and then produced a confidence interval running to minus 10.4. It failed its primary analysis. Equivalence was then demonstrated on the secondary analysis at a stricter viral load threshold, and that is the result everyone quotes.
What was measured
Proportion below 400 copies per millilitre at week 48, 95% CI -10.4% to 1.5% against a -10% equivalence limit
Effect estimate
No reviewed effect estimate exists for this record.
Limits
This entry records a failure.
From the source
Study 903 randomised 602 antiretroviral-naive patients at 81 centres to tenofovir disoproxil fumarate or stavudine, each with lamivudine and efavirenz, double-blind. In the primary intention-to-treat analysis at week 48, 239 of 299 (80%) on tenofovir against 253 of 301 (84%) on stavudine had HIV-1 RNA below 400 copies per millilitre, 95% CI -10.4% to 1.5%, which the paper states exceeded the predefined -10% equivalence limit. Equivalence was demonstrated in the secondary analyses at the 50 copies per millilitre threshold at week 48 and through 144 weeks. Through 144 weeks the K65R mutation emerged in 8 tenofovir patients against 2 on stavudine (p=0.06). The trial produced the finding that made tenofovir the backbone drug it became, and it was a metabolic one: triglycerides rose 1 mg/dL against 134 mg/dL, total cholesterol 30 against 58 mg/dL, and investigator-reported lipodystrophy occurred in 9 of 299 (3%) against 58 of 301 (19%), p<0.001. Fracture counts and renal safety were similar between arms.
Written into the record, not signed off as a reviewed claim
Hepatitis B: 76% suppressed against 13% on the drug it replaced
In plain words
In hepatitis B patients carrying the e antigen, tenofovir drove three quarters below the detection threshold at 48 weeks against one in eight on adefovir. That is one of the largest margins any antiviral has produced against an active comparator.
What was measured
Proportion with HBV DNA below 400 copies per millilitre at week 48, and histological improvement on paired biopsy
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
Two double-blind phase 3 trials (NCT00116805 in HBeAg-negative disease, NCT00117676 in HBeAg-positive disease) randomised patients 2:1 to tenofovir disoproxil fumarate 300 mg or adefovir dipivoxil 10 mg for 48 weeks. The composite primary endpoint of HBV DNA below 400 copies per millilitre with histological improvement favoured tenofovir in both studies (p<0.001). Viral suppression alone was 93% against 63% in HBeAg-negative patients (p<0.001) and 76% against 13% in HBeAg-positive patients (p<0.001). Alanine aminotransferase normalised in 68% against 54% of HBeAg-positive patients (p=0.03) and hepatitis B surface antigen was lost in 3% against 0% (p=0.02). No amino acid substitution conferring phenotypic resistance to tenofovir developed in any patient at week 48, and the response was the same in lamivudine-experienced patients as in lamivudine-naive ones.
Written into the record, not signed off as a reviewed claim
Cirrhosis reversed on repeat biopsy in 74% of those who had it at baseline
In plain words
This is the rarest kind of evidence in this repository: not a blood marker but a piece of liver, taken twice, five years apart, and read for scarring. Of 96 patients who had cirrhosis at the start, 71 no longer did. Three of 252 without cirrhosis developed it.
What was measured
Paired liver biopsy at baseline and week 240: Knodell necroinflammatory score and Ishak fibrosis stage
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
Patients from the two 48-week randomised hepatitis B trials entered a seven-year open-label extension with a prespecified repeat liver biopsy at week 240. Of 641 who received randomised treatment, 585 (91%) entered the open-label phase and 489 (76%) completed 240 weeks; 348 (54%) had biopsy results at both baseline and week 240. Histological improvement, defined as a reduction of at least 2 points in the Knodell necroinflammatory score without worsening fibrosis, occurred in 304 of 348 (87%), and fibrosis regression of at least 1 Ishak unit in 176 of 348 (51%), p<0.0001. Of the 96 patients (28%) with Ishak score 5 or 6 at baseline, 71 (74%) no longer met the cirrhosis threshold, while 3 of 252 without baseline cirrhosis progressed to it, p<0.0001. Virological breakthrough was infrequent and was not attributable to tenofovir resistance. The honest limit on this result is that the 348 patients biopsied twice are a little over half of those randomised, and the extension arm was open-label with no comparator.
Written into the record, not signed off as a reviewed claim
Prevention where it was taken: 44% in iPrEx, 67% and 75% in Partners PrEP
In plain words
Two placebo-controlled trials established that a daily tablet stops HIV being acquired. In men who have sex with men and transgender women the reduction was 44%. In heterosexual serodiscordant couples in Kenya and Uganda it was 67% for tenofovir alone and 75% with emtricitabine added.
What was measured
Incident HIV-1 infection against placebo: 44% (95% CI 15 to 63), 67% (44 to 81) and 75% (55 to 87)
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
iPrEx (NCT00458393) randomised 2,499 HIV-seronegative men and transgender women who have sex with men to daily emtricitabine-tenofovir disoproxil or placebo, followed for 3,324 person-years. 100 infections occurred during follow-up, 36 in the active group against 64 on placebo, a 44% reduction (95% CI 15 to 63, p=0.005). Partners PrEP (NCT00557245) enrolled 4,758 serodiscordant heterosexual couples and followed 4,747; 82 infections occurred, 17 on tenofovir (0.65 per 100 person-years), 13 on tenofovir-emtricitabine (0.50) and 52 on placebo (1.99), relative reductions of 67% (95% CI 44 to 81, p<0.001) and 75% (95% CI 55 to 87, p<0.001). The difference between the two active arms was not significant (p=0.23), and both reduced incidence in men and in women.
Written into the record, not signed off as a reviewed claim
Two large prevention trials in African women reported no effect at all
In plain words
FEM-PrEP randomised 2,120 women and found no difference. VOICE randomised 5,029 and produced a point estimate of minus 49% for tenofovir alone, meaning the drug arm did numerically worse than placebo. Both trials stopped early. In both, the drug was measured in blood and found in fewer than a third of samples.
What was measured
Incident HIV-1 infection by intention to treat: hazard ratio 0.94 (95% CI 0.59 to 1.52) and 1.49 (0.97 to 2.29)
Effect estimate
No reviewed effect estimate exists for this record.
Limits
This entry records a failure.
From the source
FEM-PrEP (NCT00625404) randomised 2,120 HIV-negative women in Kenya, South Africa and Tanzania to daily emtricitabine-tenofovir disoproxil or placebo. 33 infections occurred in the active group (4.7 per 100 person-years) against 35 on placebo (5.0), hazard ratio 0.94 (95% CI 0.59 to 1.52, p=0.81). The trial was stopped on 18 April 2011 for lack of efficacy. Fewer than 40% of uninfected women in the active group had evidence of recent pill use at visits matched to the infection window. VOICE (NCT00705679) randomised 5,029 women in South Africa, Uganda and Zimbabwe to oral tenofovir, oral tenofovir-emtricitabine, tenofovir vaginal gel or placebo, with 312 infections over 5,509 person-years. Modified intention-to-treat effectiveness was -49.0% for tenofovir (hazard ratio 1.49, 95% CI 0.97 to 2.29), -4.4% for tenofovir-emtricitabine (1.04, 0.73 to 1.49) and 14.5% for the gel (0.85, 0.61 to 1.21). Tenofovir was detected in 30%, 29% and 25% of sampled plasma. Detection was negatively associated with the characteristics that predicted acquisition, meaning the women at highest risk were the least likely to have drug on board.
Written into the record, not signed off as a reviewed claim
The field read those failures as "the drug does not work in women", then re-read them as "the pills were not taken"
In plain words
For a period after FEM-PrEP and VOICE, the working conclusion was that oral prevention did not protect African women, and biological explanations were proposed for why. The re-reading came from the drug concentrations measured inside the same trials, and from Partners PrEP, which ran in the same region, enrolled women, and worked.
What was measured
That FEM-PrEP and VOICE would have demonstrated efficacy if participants had taken the tablets — supported by measured drug concentrations, but a counterfactual that no randomised comparison in those trials tested
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
The two failures are intention-to-treat results and are correct as such: randomised to the drug, those women were not protected. The re-reading rests on measured quantities rather than on argument. VOICE detected tenofovir in 30% or fewer of plasma samples in each active arm. FEM-PrEP found recent pill use in fewer than 40%. iPrEx found study drug in 51% of seronegative participants against 9% of those who acquired HIV (p<0.001), which is the same relationship measured in the trial that succeeded. Partners PrEP, in the same geography with a couples-based design and high adherence, produced 67% and 75% reductions and reduced incidence in women specifically. What is measured, then, is that protection tracks drug concentration. What remains an inference is the counterfactual: that these particular trials would have shown efficacy had adherence been high, which no analysis of an unrandomised subgroup can establish. Both statements need to be on the page. Retiring the first conclusion was right; treating the adherence account as though it were a randomised finding is a second mistake in the opposite direction.
Written into the record, not signed off as a reviewed claim
The renal and bone toxicity is real, labelled, and smaller than the reputation
In plain words
Tenofovir disoproxil damages the kidney tubule in some people and that is on the label. But when it was given to thousands of HIV-negative adults with normal kidneys and measured properly, the average kidney function loss was about 1.2 mL/min and the proportion with a serious drop was no higher than on placebo.
What was measured
That the small, non-progressive renal and bone changes measured in HIV-negative prevention populations describe the risk in people treated for HIV for decades
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
A per-protocol safety analysis of 4,640 Partners PrEP participants found mean eGFR change attributable to the drug of -1.23 mL/min/1.73 m2 (95% CI -2.06 to -0.40, p=0.004) for tenofovir alone and -1.59 (95% CI -2.44 to -0.74, p<0.001) with emtricitabine, appearing by one month, stable to twelve months, and waning thereafter. Confirmed declines of 25% or more occurred in 1.8% and 2.5% by 24 months against 1.3% on placebo, which was not statistically different. In the iPrEx bone substudy of 498 participants, spine bone mineral density fell by a net 0.91% (95% CI -1.44 to -0.38, p=0.001) and hip by 0.61% (-0.96 to -0.27, p=0.001) by week 24, with no further significant change afterwards, with the loss correlating inversely with intracellular tenofovir diphosphate, no difference in fractures (p=0.62), and a tendency to rebound after discontinuation. The measured harm is therefore small, front-loaded and partly reversible in people with normal renal function. Extrapolating from that to the treated HIV population with decades of exposure, lower baseline renal reserve and concomitant boosters is an inference, and it runs in the direction of underestimating harm rather than overestimating it. Proximal tubulopathy and Fanconi syndrome are labelled and do occur; what is not established is how often.
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What is not here
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Felt, measured, or meaningful — found nothing in the sources checked.
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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 prodrug of tenofovir that terminates the DNA chain of both HIV-1 and hepatitis B; it drove 84% of treatment-naive patients below 400 copies per millilitre against 73% on the zidovudine regimen it replaced, reversed cirrhosis on repeat biopsy in 74 of 96 hepatitis B patients who had it at baseline, and cut HIV acquisition by 67% in serodiscordant couples who took it — and by nothing at all in two large trials where blood levels showed most participants did not.
Recorded evidence blocks (11)
Q1
On the Tenofovir Disoproxil label: indicated for what?
"Tenofovir disoproxil fumarate is a nucleotide analog HIV-1 reverse transcriptase inhibitor and an HBV reverse transcriptase inhibitor and is indicated: in combination with other antiretroviral agents for the treatment of HIV-1 infection in adults and pediatric patients 2 years of age and older weighing at least 35 kg.…": indications and usage on Tenofovir Disoproxil's label. DailyMed label · e0ae0aa2-3baa-4b75-9e85-68b5338c3c14 · 2026-07-13
Q2
238 registered trials of Tenofovir Disoproxil — at which phases?
Registered studies posting no result
167 of 238
238 registered studies of Tenofovir Disoproxil: 58 phase2, 56 phase4, 48 phase3, 32 phase1, 27 na, 25 na or unstated, 3 early phase1. CLINICALTRIALS_SNAPSHOT · 2026-09-01
"study was withdrawn before any participants were recruited and enrolled"; 18 of 238 registered studies
Show the evidence
Trial
NCT00087464
withdrawn; "study was withdrawn before any participants were recruited and enrolled"
NCT00679926
terminated; "Lack of enrollment"
NCT00998582
terminated; "Low enrollment"
NCT01528865
withdrawn; "Funding was removed."
NCT01872988
terminated; "Difficult in patient enrollment"
NCT02322099
terminated; "Due to the COVID-19 pandemic the study was terminated prematurely"
12 further recorded trials
NCT02452528
terminated; "Company decision to discontinue trial"
NCT02454764
withdrawn; "lack of funds"
NCT02577029
terminated; "Company decision to discontinue trial"
NCT03032536
terminated; "Sponsor decision."
NCT03304717
withdrawn; "Results from other clinical trials on AGS established baricitinib as standard of care treatment. Thanks to the knowledge gained in the clinical treatment of AGS, a clinical trial around the effects of RTI in AGS is no longer relevant at…"
NCT03887702
terminated; "inability to accrue"
NCT04820686
terminated; "Sponsor decision"
NCT04847440
terminated; "Terminated by the Sponsor"
NCT05005507
terminated; "A strategic decision was made to not further execute the study. This decision was not based on a safety concern."
NCT05238844
terminated; "Sponsor stopped due to partner collaboration ending"
NCT05423106
terminated; "Strategic business decision, not due to safety concerns"
NCT05550519
withdrawn; "Sponsor Decision after re-evaluation of strategy in the context of recruitment timelines projection"
recorded 2026-09-01 · last checked 2026-09-04
Q4
Human studies of Tenofovir Disoproxil used Tenofovir disoproxil fumarate (TDF) 300 mg — over how long?
Human studies of Tenofovir Disoproxil used "Tenofovir disoproxil fumarate (TDF) 300 mg". ClinicalTrials.gov · 2026-09-01
16 recorded entries; human; tablet, oral; also "GSK548470 300 mg tablet", "tenofovir disoproxil fumarate 300mg per day", "Viread 300mg"
Tenofovir Disoproxil's half-life is 17 hours — which schedules were studied?
17 hours, the half-life Tenofovir Disoproxil's label states: "Following single dose, oral administration of tenofovir disoproxil fumarate, the terminal elimination half-life of tenofovir is approximately 17 hours." DailyMed label · e0ae0aa2-3baa-4b75-9e85-68b5338c3c14 · 2026-07-13
bioavailability 25 %.
Show the evidence
half lifepharmacokinetics
17 hours; Following single dose, oral administration of tenofovir disoproxil fumarate, the terminal elimination half-life of tenofovir is approximately 17 hours.
bioavailabilitypharmacokinetics
25 %; The oral bioavailability of tenofovir from tenofovir disoproxil fumarate in fasted subjects is approximately 25%.
metabolismpharmacokinetics
Metabolism and Elimination In vitro studies indicate that neither tenofovir disoproxil nor tenofovir are substrates of CYP enzymes.
recorded 2026-07-13 · last checked 2026-09-04
Q6
Which running trial of Tenofovir Disoproxil could settle lifespan?
NCT03920618 measures Survival rate in the follow-up, reading out 2024-12-31.
1 open trial; n 150; "Three Types of Nucleotide/Nucleoside Analogues Treatment in HBV Related ACLF"
Show the evidence
TrialNCT03920618
"Three Types of Nucleotide/Nucleoside Analogues Treatment in HBV Related ACLF"; n 150; "Survival rate in the follow-up"; 2024-12-31
Q7
Which 80 trials of Tenofovir Disoproxil posted no result?
Posted no result
80 of 80 completed trials
Registrations
NCT00036634, NCT00270556, NCT00033163, NCT00027339, NCT00028366 and NCT00050895, and 74 more
Completion dates
oldest 2003-02; newest 2024-06-26
Show the evidence
Trial
NCT00036634
2003-02
NCT00270556
2004-10
NCT00033163
2005-05
NCT00027339
2005-06
NCT00028366
2005-07
NCT00050895
2006-03
14 further recorded trials
NCT00122486
2006-03
NCT00034086
2006-06
NCT00324688
2006-06
NCT00344981
2006-11
NCT00100581
2007-01
NCT00106379
2007-01
NCT00102206
2007-05
NCT00109603
2007-11
NCT00648817
2007-12
NCT00051831
2008-05
NCT00260078
2009-04
NCT01074645
2009-10
NCT00115609
2009-11
NCT00903084
2010-06
Q8
At the median, Tenofovir Disoproxil's trials enrolled 104 people — anything larger?
Median enrolment
104
Largest enrolment
7350
Registered trials counted
234
Q9
What do 5568 spontaneous reports say about Tenofovir Disoproxil — 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.
Tenofovir Disoproxil appears in spontaneous reports to regulators. Across the 10 most-reported reaction terms, 5568 reaction mentions were counted: drug resistance 802; virologic failure 802; abortion spontaneous 592; osteoporosis 559. FAERS via Open Targets · CHEMBL1486 · 2026-06-24
Show the evidence
drug resistance
802
virologic failure
802
abortion spontaneous
592
osteoporosis
559
blood creatinine increased
541
pathogen resistance
518
4 more recorded rows
viral mutation identified
513
renal failure
454
renal failure acute
414
immune reconstitution inflammatory syndrome
373
recorded 2026-06-24 · last checked 2026-09-04
Q10
Which 10 reactions does Tenofovir Disoproxil's label not list?
Assessment of Drug Interactions At concentrations substantially higher (~300-fold) than those observed in vivo, tenofovir did not inhibit in vitro drug metabolism mediated by any of the following human CYP isoforms: CYP3A4, CYP2D6, CYP2C9, or CYP2E1.
pharmacokinetics
However, a small (6%) but statistically significant reduction in metabolism of CYP1A substrate was observed.
pharmacokinetics
TDF is a substrate of P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) transporters.
clinical_pharmacology
Assessment of Drug Interactions At concentrations substantially higher (~300-fold) than those observed in vivo, tenofovir did not inhibit in vitro drug metabolism mediated by any of the following human CYP isoforms: CYP3A4, CYP2D6, CYP2C9, or CYP2E1.
clinical_pharmacology
However, a small (6%) but statistically significant reduction in metabolism of CYP1A substrate was observed.
clinical_pharmacology
TDF is a substrate of P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) transporters.
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
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