This page shows what was measured, who it was measured in, and what that does not settle.
What Tenofovir alafenamide does in the body
HIV-1 infection, HIV prevention, and chronic hepatitis B
Tenofovir is the molecule that does the work, and on its own it barely gets into a cell. Both tenofovir products are wrappers built to smuggle it in, and they differ only in where the wrapper comes off. The older one falls apart within minutes in the bloodstream, so most of the dose travels as free tenofovir past the kidney and the skeleton. This one holds together in plasma and is cut open by an enzyme inside the cells the virus infects, so a much smaller dose puts more drug where the virus is and much less everywhere else.
What happened in people
Hip bone mineral density change of -0.29% against -2.16% and proteinuria change of -3% against +20%, consistently across four randomised trials
✎ 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.
That the bone-density and renal-biomarker differences translate into fewer fractures or fewer cases of renal failure — the registration paper states in its own Interpretation that it was not powered to assess either
Where it acts
Cytoplasm of CD4-positive T cells and of hepatocytes, where the prodrug is unwrapped and phosphorylated
Kind of result
A number that stands in for health
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 · FWF6Q91TZO · read 2026-08-29
Its recorded molecular formula is C21H29O5N6P.
US prescribing information · 72e6b33c-0351-4070-9172-eeaa186c01d2 · read 2026-08-30
Where each sentence above came from
No recorded sentence describes the change this makes in a way that stands on its own. 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 132 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.
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.
Formulation
A formulation is the exact made-up form a substance comes in.
A picture of it, and where the picture fails
It is like the difference between a whole bean and instant coffee.
Where that stops being true. Coffee tastes different. A formulation can change how much reaches the blood.
What people get wrong. Two products with the same name are assumed to behave the same. They often do not.
The specific composition and physical form of a product, including salt, excipients and release profile.
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 HBV DNA below 29 IU/mL at week 48 in HBeAg-negative chronic hepatitis B
64% versus 67%, adjusted difference -3.6% (95% CI -9.8 to 2.6), p=0.25, within the 10% margin
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 point estimate favours the comparator. Non-inferiority was met, which is a different statement from equivalence, and the difference is reported here because rounding it away is how a non-inferiority result becomes a marketing claim.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Oral film-coated tablet, as a single agent and as a component of fixed-dose combinations
Interval reported. 95% CI -9
Written into the record, not signed off as a reviewed claim.
IRR 0.47 (95% CI 0.19 to 1.15) against a non-inferiority margin of 1.62; superiority not established
Repeated elsewhere
Unreplicated
What this does not prove. Meeting one endpoint in one population does not carry to other goals or other people.
The limits of this study, and where it came from
Main limit. No cisgender women were enrolled. The resulting FDA indication excludes individuals at risk from receptive vaginal sex, in the label text itself.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Oral film-coated tablet, as a single agent and as a component of fixed-dose combinations
Interval reported. 95% CI 0
Written into the record, not signed off as a reviewed claim.
Percentage change in body weight at 48 weeks after switching off an integrase inhibitor, off tenofovir alafenamide, or both, in people with HIV and obesity
Between-arm difference 1.36 percentage points (97.5% CI -1.20 to 3.92) and -0.89 (-3.34 to 1.57); no arm showed a clinically meaningful change
Repeated elsewhere
Unreplicated
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 trial also found no treatment differences in fasting lipids, insulin resistance, fat mass or bone mineral density, which is a null result on bone in a head-to-head prodrug comparison and sits awkwardly beside the registration data.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Oral film-coated tablet, as a single agent and as a component of fixed-dose combinations
Interval reported. Not recorded in this summary
Written into the record, not signed off as a reviewed claim.
RNAWiki holds 5 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 alafenamide
What a person takes: Oral film-coated tablet, as a single agent and as a component of fixed-dose combinations.
The measurement behind this step
Taken once daily. Absorption depends on P-glycoprotein, so strong inducers such as rifampicin, rifabutin, carbamazepine and St John wort lower exposure enough that co-administration is contraindicated or not recommended on the label. Unlike tenofovir disoproxil it is used down to a creatinine clearance of 15 mL/min in the approved combinations.
Getting in
Swallowed as a wrapper that does not fall apart on the way
A small tablet, once a day. The active drug is sealed inside a chemical wrapper that is built to stay closed while it is in the bloodstream, which is the whole point of the molecule.
──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 alafenamide is a phosphonoamidate prodrug: a phenol ester and an L-alanine isopropyl ester amidate mask the phosphonate that would otherwise keep the molecule out of cells. Plasma half-life of the intact prodrug is on the order of tens of minutes rather than the seconds that tenofovir disoproxil survives, and the practical consequence is that plasma tenofovir exposure falls by roughly 90% while the dose falls from 300 mg to 25 mg.
It is opened by an enzyme that only lives inside the target cell
Once inside a T cell or a liver cell, a resident enzyme cuts the wrapper off and releases the drug where it is needed. Cells that are not targets never open 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
Cathepsin A performs the first hydrolysis in lymphoid cells and carboxylesterase 1 does it in hepatocytes, removing the alaninyl ester and triggering spontaneous loss of the phenol to give tenofovir monophosphate directly. The cell-type distribution of those two hydrolases is why the same molecule concentrates in CD4-positive T cells for HIV and in hepatocytes for hepatitis B, and why the drug is a P-glycoprotein substrate whose absorption is destroyed by rifampicin.
The cell adds phosphates until it looks like a DNA building block
The released drug is not active yet. The cell attaches phosphate groups to it, and the finished molecule is a near-perfect impostor of one of the four letters DNA is built 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 monophosphate is converted by nucleoside diphosphate kinase and adenylate kinase to tenofovir diphosphate, the pharmacologically active species, which is the analogue of deoxyadenosine triphosphate. The intracellular half-life of tenofovir diphosphate in PBMCs is long, on the order of days, which is the pharmacological basis for once-daily dosing and for the forgiveness of a missed dose.
The copying enzyme inserts it, and then cannot add anything after it
Reverse transcriptase picks it up as though it were a normal letter and stitches it into the growing chain. It has no attachment point on the far end, so the next letter can never be added and the copy stops there.
╌╌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 diphosphate competes with dATP for the polymerase active site and is incorporated. The acyclic phosphonomethoxypropyl linker carries no 3-prime hydroxyl, so obligate chain termination follows incorporation. The same chemistry works on HIV-1 reverse transcriptase and on the reverse transcriptase domain of the hepatitis B polymerase, which is why one molecule covers two viruses. The signature HIV resistance mutation is K65R, which reduces incorporation and carries a fitness cost.
Virus falls, and less free drug ever reaches the kidney or the skeleton
Viral load drops the way it does on the older prodrug. The measured difference is elsewhere: less of the active drug circulates past the kidney tubule and the bone, and the scans and urine tests show it.
──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
Viral suppression was statistically indistinguishable from tenofovir disoproxil in all four registration trials. What differed were the surrogates: hip bone mineral density change of -0.29% against -2.16% in HBeAg-negative hepatitis B, proteinuria change of -3% against +20% in treatment-naive HIV. Free tenofovir is a substrate of the OAT1 and OAT3 transporters that concentrate it in the proximal tubule, so lowering plasma tenofovir lowers tubular loading, which is the mechanistic account of every one of those numbers.
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 one of the Gilead fixed-dose HIV combinations, people taking Descovy for pre-exposure prophylaxis, and adults and older children with chronic hepatitis B who take Vemlidy as a single tablet.
Who is missing from the studies
Which groups were under-represented in the studies has not been recorded for this substance. Pregnancy, breastfeeding, children, older adults, and people with liver or kidney conditions are commonly excluded from trials; nothing here says whether they were.
What the label states about particular groups
On pediatric, the label states: “Safety and effectiveness of VEMLIDY has not been established in pediatric patients with chronic HBV infection who are less than 6 years of age or weigh less than 25 kg.”
US prescribing information · 72e6b33c-0351-4070-9172-eeaa186c01d2 · read 2026-08-30
On older people, the label states: “In clinical trials, VEMLIDY was administered to 89 subjects aged 65 and over.”
US prescribing information · 72e6b33c-0351-4070-9172-eeaa186c01d2 · read 2026-08-30
On people who are pregnant, the label states: “Exposure Registry There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to VEMLIDY during pregnancy.”
US prescribing information · 72e6b33c-0351-4070-9172-eeaa186c01d2 · read 2026-08-30
On people who are breastfeeding, the label states: “Risk Summary Data from the published literature report the presence of TAF and tenofovir in human milk.”
US prescribing information · 72e6b33c-0351-4070-9172-eeaa186c01d2 · read 2026-08-30
On people with reduced liver function, the label states: “The safety and efficacy of VEMLIDY in patients with decompensated cirrhosis (Child-Pugh B or C) have not been established; therefore, VEMLIDY is not recommended in patients with decompensated (Child-Pugh B or C) hepatic impairment [see Dosage and Administration (2.4) and Clinical Pharmacology (12.3) ] .”
US prescribing information · 72e6b33c-0351-4070-9172-eeaa186c01d2 · read 2026-08-30
On people with reduced kidney function, the label states: “VEMLIDY is not recommended in patients with ESRD (estimated creatinine clearance below 15 mL per minute by Cockcroft-Gault method) who are not receiving chronic hemodialysis as the safety of VEMLIDY has not been established in this population [see Dosage and Administration (2.3) and Clinical Pharmacology (12.3) ].”
US prescribing information · 72e6b33c-0351-4070-9172-eeaa186c01d2 · read 2026-08-30
Where the result stopped carrying
A meta-analysis of 13 randomised prevention trials in 15,678 participants found no detectable difference in fractures (217/5,789 against 189/5,795) or creatinine elevations for the older prodrug against control
The HBeAg-positive registration trial produced a negative point estimate, -3.6%, that passed non-inferiority and is routinely quoted as if the two arms had tied
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.
A different form was studied
The studied form is not the form on the shelf.
On this record: This record is linked to 1 related forms. Evidence does not carry across all of them.
The evidence may simply be wrong
Small early studies often do not hold up.
On this record: RNAWiki has not yet published a reviewed conclusion for this use.
Other reasons RNAWiki checked and found nothing for (10)
It was studied for a different goal
The studies measured something else entirely. Nothing in this record points to this reason.
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 film-coated tablet, as a single agent and as a component of 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. Absorption depends on P-glycoprotein, so strong inducers such as rifampicin, rifabutin, carbamazepine and St John wort lower exposure enough that co-administration is contraindicated or not recommended on the label. Unlike tenofovir disoproxil it is used down to a creatinine clearance of 15 mL/min in the approved 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.
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 on every tenofovir product, and hepatic function must be monitored after stopping. Lactic acidosis and severe hepatomegaly with steatosis are labelled class effects of nucleoside analogues. Bone mineral density falls less than on tenofovir disoproxil but still falls. LDL cholesterol and total cholesterol run higher than on tenofovir disoproxil, and body weight runs higher; whether that reflects a lipid-raising and weight-raising effect of this drug or the loss of a lipid-lowering and weight-suppressing effect of the older one is not settled.
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 film-coated tablet, as a single agent and as a component of 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
Absorption depends on P-glycoprotein, so strong inducers such as rifampicin, rifabutin, carbamazepine and St John wort lower exposure enough that co-administration is contraindicated or not recommended on the label. Unlike tenofovir disoproxil it is used down to a creatinine clearance of 15 mL/min in the approved 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.
Recorded notes on which forms are sold and how they compare.
No source is stored against this line.
What is recorded as being sold
35 products list this as an active ingredient in the United States drug directory. 15 of them contain it and nothing else.
FDA National Drug Code directory · 42931-251 · read 2026-08-29
They are sold as powder, tablet and tablet, film coated, taken oral.
FDA National Drug Code directory · 42931-251 · 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 · 42931-251 · read 2026-08-29
7 published labels name it as an active ingredient. 1 of them describe this substance alone, which is where its own label text on this page comes from.
US prescribing information · 34784acf-15ed-4715-b504-eb30430518e9 · read 2026-08-29
Those labels are classed as human prescription drug.
US prescribing information · 34784acf-15ed-4715-b504-eb30430518e9 · read 2026-08-29
VEMLIDY is oral at 3 DOSAGE FORMS AND STRENGTHS Tablets: 25 mg of tenofovir alafenamide (equivalent to 28 mg of tenofovir alafenamide fumarate) — yellow, round, film-coated tablets, debossed with "GSI" on one side of the tablet and "25" o…, recorded as fda label in effect 2025-07-14 in the United States.
US prescribing information · 72e6b33c-0351-4070-9172-eeaa186c01d2 · read 2026-08-30
Evidence carries across two names for one substance. It does not carry across a salt, a mirror form or a mixture.
Evidence on this page does not automatically apply to this one.
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 alafenamide 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 the bone-density and renal-biomarker differences translate into fewer fractures or fewer cases of renal failure — the registration paper states in its own Interpretation that it was not powered to assess either
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 DISCOVER efficacy extends to people at risk from receptive vaginal sex, an inference the FDA label explicitly declines to make
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 tenofovir alafenamide causes the weight gain attributed to it, which a randomised 48-week switch trial did not reverse by removing it
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 alafenamide 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.
HBeAg-negative hepatitis B: 94% against 93%, with a third of the bone loss
In plain words
In 425 people with hepatitis B who did not carry the e antigen, 94% on tenofovir alafenamide had undetectable virus at 48 weeks against 93% on the older prodrug. The difference in bone density was much larger than the difference in virus.
What was measured
Proportion with HBV DNA below 29 IU/mL at week 48, plus mean percentage change in hip and spine bone mineral density and median change in eGFR
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
GS-US-320-0108 (NCT01940341) randomised 426 HBeAg-negative patients 2:1 to tenofovir alafenamide 25 mg or tenofovir disoproxil fumarate 300 mg, double-blind, in 105 centres across 17 countries. At week 48, 268 of 285 (94%) versus 130 of 140 (93%) had HBV DNA below 29 IU/mL, difference 1.8% (95% CI -3.6 to 7.2, p=0.47), meeting the 10% non-inferiority margin. Mean percentage change in hip bone mineral density was -0.29% (95% CI -0.55 to -0.03) against -2.16% (-2.53 to -1.79), adjusted difference 1.87% (95% CI 1.42 to 2.32, p<0.0001); spine was -0.88% against -2.51%, adjusted difference 1.64% (95% CI 1.01 to 2.27, p<0.0001). Median change in estimated glomerular filtration rate was -1.8 mL/min (IQR -7.8 to 6.0) against -4.8 mL/min (-12.0 to 3.0), p=0.004, while the mean serum creatinine change did not differ (p=0.32).
Written into the record, not signed off as a reviewed claim
HBeAg-positive hepatitis B: 64% against 67%, non-inferior and numerically behind
In plain words
In the harder half of hepatitis B, where people start with far more virus, 64% on the new prodrug reached undetectable against 67% on the old one. That is a negative point estimate that still passed the non-inferiority test, and it is worth stating plainly rather than rounding into a win.
What was measured
Proportion with HBV DNA below 29 IU/mL at week 48, adjusted difference -3.6% (95% CI -9.8 to 2.6)
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
GS-US-320-0110 (NCT01940471) randomised 875 HBeAg-positive patients 2:1 across 161 centres in 19 countries; 873 received treatment. At week 48, 371 of 581 (64%) on tenofovir alafenamide against 195 of 292 (67%) on tenofovir disoproxil fumarate had HBV DNA below 29 IU/mL, adjusted difference -3.6% (95% CI -9.8 to 2.6, p=0.25), within the prespecified 10% margin. Hip bone mineral density changed by -0.10% (95% CI -0.29 to 0.09) against -1.72% (-2.02 to -1.41), adjusted difference 1.62 (1.27 to 1.96, p<0.0001); spine -0.42% against -2.29%, adjusted difference 1.88 (1.44 to 2.31, p<0.0001). Mean serum creatinine rose 0.01 mg/dL against 0.03 mg/dL (p=0.02). Grade 3 or 4 laboratory abnormalities occurred in 32% and 33% of the two arms, most commonly ALT elevation.
Written into the record, not signed off as a reviewed claim
HIV-1, 1,733 treatment-naive patients: 92% against 90%, proteinuria down 3% against up 20%
In plain words
The two trials that put tenofovir alafenamide into HIV combinations found 92% of patients suppressed at 48 weeks against 90% on the older prodrug. Protein leaking into urine, a marker of kidney tubule stress, fell slightly on the new drug and rose by a fifth on the old one.
What was measured
Proportion with HIV-1 RNA below 50 copies per millilitre at week 48, plus prespecified renal and bone endpoints
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
Studies 104 and 111 (NCT01780506 and NCT01797445) recruited 1,744 treatment-naive adults from 178 centres in 16 countries and treated 1,733, randomised double-blind to elvitegravir-cobicistat-emtricitabine with either tenofovir alafenamide 10 mg or tenofovir disoproxil fumarate 300 mg. At week 48, 800 of 866 (92%) against 784 of 867 (90%) had HIV-1 RNA below 50 copies per millilitre, adjusted difference 2.0% (95% CI -0.7 to 4.7) against a 12% non-inferiority margin. Mean serum creatinine rose 0.08 against 0.12 mg/dL (p<0.0001); median percentage change in proteinuria was -3 against +20 (p<0.0001); spine bone mineral density changed -1.30% against -2.86% and hip -0.66% against -2.95% (both p<0.0001).
Written into the record, not signed off as a reviewed claim
The registration paper says the surrogate is a surrogate, in its own conclusion
In plain words
Every advantage this drug has over the cheap version is a laboratory measurement: bone density on a scan, creatinine and protein in urine. Nobody has run a trial big enough to see whether that turns into fewer broken bones or fewer people on dialysis, and the authors of the registration trial said so in print.
What was measured
That smaller 48-week declines in bone mineral density and smaller changes in renal biomarkers translate into fewer fractures and fewer cases of renal failure
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
The interpretation section of the phase 3 HIV programme reads: "Although these studies do not have the power to assess clinical safety events such as renal failure and fractures, our data suggest that E/C/F/tenofovir alafenamide will have a favourable long-term renal and bone safety profile." The hepatitis B trials close the same way, with "longer term follow-up is needed to better understand the clinical impact of these changes." The measured quantities are real and consistently in the same direction across four randomised trials. The step from a 1.6 to 2.3 percentage-point difference in bone mineral density over 48 weeks to a difference in fracture incidence is an extrapolation, and the size of that extrapolation is what the price difference on this page is being charged for.
Written into the record, not signed off as a reviewed claim
In 15,678 randomised prevention participants, the harm being avoided was not visible
In plain words
A meta-analysis pooled thirteen randomised prevention trials of the older tenofovir against placebo or no treatment. Fractures: 217 of 5,789 on the drug against 189 of 5,795 on control. Serious adverse events: 9.4% against 10.1%. The clinical events the newer prodrug was designed to prevent were not detectable in the largest randomised dataset that exists.
What was measured
Pooled incidence of fractures, creatinine elevations, grade 3/4 adverse events and serious adverse events across 13 randomised trials
Effect estimate
No reviewed effect estimate exists for this record.
Limits
This entry records a failure.
From the source
Pilkington, Hill and colleagues systematically reviewed 13 randomised pre-exposure prophylaxis trials covering 15,678 participants in relevant arms. Grade 3 or 4 adverse events occurred in 1,306 of 7,504 on treatment (17.4%) against 1,259 of 7,502 on control (16.8%), difference 0% (95% CI -1% to +2%). Serious adverse events were 740 of 7,843 (9.4%) against 795 of 7,835 (10.1%), difference 0% (95% CI -1% to +1%). Creatinine elevations were 8 of 7,843 against 4 of 7,835, difference 0% (95% CI 0% to 0%). Fractures were 217 of 5,789 against 189 of 5,795, difference 0% (95% CI 0% to 1%). This does not refute tenofovir disoproxil toxicity: the population is HIV-negative, mostly young, with normal renal function at entry and short follow-up, which is not the population in whom the classic tubulopathy is described. What it does is put a ceiling on how large the avoidable harm can be in the setting where the two prodrugs compete most directly and where the price gap is widest.
Written into the record, not signed off as a reviewed claim
Weight gain was blamed on tenofovir alafenamide, then a randomised switch trial removed it and nothing happened
In plain words
Cohort studies and comparative trials found people on tenofovir alafenamide heavier than people on the older prodrug, and the drug acquired a reputation for causing weight gain. A randomised trial then took obese patients off it and off their integrase inhibitor for 48 weeks. Weight did not meaningfully move in any arm, and the differences between arms were compatible with zero.
What was measured
That tenofovir alafenamide causes the weight gain associated with it, and that removing it reverses that weight
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
ACTG A5391, the Do IT study (NCT04636437), randomised 147 people with HIV and obesity who were suppressed on an integrase inhibitor with tenofovir alafenamide and emtricitabine into three open-label arms: switch to doravirine with tenofovir alafenamide-emtricitabine, switch to doravirine with tenofovir disoproxil-emtricitabine, or continue. 145 initiated. Median entry BMI was 34.9 kg/m2 and median time on the starting regimen 3.4 years; 49% were female and 53% Black. At 48 weeks estimated mean weight change was -0.47% (95% CI -2.09 to 1.14), -2.73% (-4.22 to -1.23) and -1.84% (-3.37 to -0.30). The between-arm estimates were 1.36 percentage points (97.5% CI -1.20 to 3.92) for doravirine against integrase inhibitor with the same backbone, and -0.89 percentage points (-3.34 to 1.57) for the tenofovir disoproxil switch against continuing. The authors also report no treatment differences in fasting lipids, insulin resistance, fat mass or bone mineral density. A separate pilot switching people to doravirine-lamivudine-tenofovir disoproxil closed for futility after enrolling four of a planned 25, so the reversal question has been asked twice and answered once.
Written into the record, not signed off as a reviewed claim
DISCOVER: 7 infections against 15, non-inferior, and not superior
In plain words
The largest prevention trial randomised 5,387 people to one prodrug or the other. Seven people on tenofovir alafenamide acquired HIV against fifteen on tenofovir disoproxil. That looks like a win, but the confidence interval runs from 0.19 to 1.15, which includes no difference, so the trial proved non-inferiority and nothing more.
What was measured
Incident HIV infection, incidence rate ratio 0.47 (95% CI 0.19 to 1.15) over 8,756 person-years
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
DISCOVER (NCT02842086) randomised 5,387 cisgender men who have sex with men and transgender women who have sex with men 1:1 across 94 clinics in Europe and North America, double-blind and double-dummy. Over 8,756 person-years, 22 participants acquired HIV: seven on emtricitabine-tenofovir alafenamide (0.16 per 100 person-years, 95% CI 0.06 to 0.33) against fifteen on emtricitabine-tenofovir disoproxil (0.34 per 100 person-years, 0.19 to 0.56). The incidence rate ratio was 0.47 (95% CI 0.19 to 1.15) against a prespecified non-inferiority margin of 1.62. Discontinuation for adverse events was 36 of 2,694 (1%) against 49 of 2,693 (2%). All six prespecified bone mineral density and renal biomarker endpoints favoured tenofovir alafenamide.
Written into the record, not signed off as a reviewed claim
The prevention indication has a hole in it, and the label names the hole
In plain words
DISCOVER enrolled cisgender men who have sex with men and transgender women. It enrolled no cisgender women. The FDA label therefore excludes people at risk from receptive vaginal sex, in writing, and that exclusion is not a caution: it means the question was never asked.
What was measured
That the prevention efficacy shown in cisgender men who have sex with men and transgender women extends to people at risk from receptive vaginal sex
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
The Descovy prescribing information states the indication as pre-exposure prophylaxis "excluding individuals at risk from receptive vaginal sex", with the Limitations of Use section reading "The indication does not include use of DESCOVY in individuals at risk of HIV-1 from receptive vaginal sex because effectiveness in this population has not been evaluated." The pharmacological reason this matters is that tenofovir concentrations differ substantially between rectal and cervicovaginal tissue, so the tissue at risk is not the tissue the trial measured protection in, and the older prodrug has separate randomised data in women that this one does not. Emtricitabine-tenofovir disoproxil carries no such exclusion. This is the clearest case on the page of an inference that regulators declined to make, and it is worth noticing that the regulator drew the line the marketing would not have.
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What is not here
7 questions this page could not answer
These sections were prepared and left out because there was nothing to put in them. They are listed rather than hidden, so the gaps in this record are visible.
What was measured, goal by goal — found nothing in the sources checked.
How close this is to real life — found nothing in the sources checked.
Felt, measured, or meaningful — found nothing in the sources checked.
How long anything takes — found nothing in the sources checked.
What it may clash with — found nothing in the sources checked.
Other ways to the same goal — found nothing in the sources checked.
What changed on this page — found nothing in the sources checked.
The record as stored
The full record, for auditing
Everything above is built from what is below. This layer keeps the technical vocabulary, record identifiers and every stored row, so a reader who wants to check the page can.
The older medicine-wide conclusion held in this record
Written for a clinical reader, and about the medicine as a whole rather than about one indication, population and set of trials. RNAWiki does not treat it as a programme conclusion and no reviewer has signed it off in that form. It is here word for word because it is what the record holds.
A prodrug that carries the same active molecule as tenofovir disoproxil but survives the bloodstream and is opened inside the cell instead, so a twelve-fold smaller dose matched the older prodrug on viral suppression in every head-to-head trial and beat it on bone density and kidney biomarkers, which are surrogates that the registration papers themselves said they were not powered to convert into fractures or renal failure.
Recorded evidence blocks (10)
Q1
On the Tenofovir alafenamide label: indicated for what?
"VEMLIDY is indicated for the treatment of chronic hepatitis B virus (HBV) infection in adults and pediatric patients 6 years of age and older and weighing at least 25 kg with compensated liver disease [see Clinical Studies (14) ] . VEMLIDY is a hepatitis B virus (HBV) nucleoside analog reverse transcriptase inhibitor…": indications and usage on Tenofovir alafenamide's label. DailyMed label · 72e6b33c-0351-4070-9172-eeaa186c01d2 · 2025-07-14
Q2
219 registered trials of Tenofovir alafenamide — at which phases?
Registered studies posting no result
136 of 219
219 registered studies of Tenofovir alafenamide: 62 phase3, 59 phase4, 46 phase2, 25 na or unstated, 25 phase1, 11 na, 3 early phase1. CLINICALTRIALS_SNAPSHOT · 2026-09-01
"Study was terminated due to sponsor's decision to not pursue further development of inarigivir soproxil in chronic hepatitis B."; 20 of 219 registered studies
Show the evidence
Trial
NCT03434353
terminated; "Study was terminated due to sponsor's decision to not pursue further development of inarigivir soproxil in chronic hepatitis B."
NCT03472326
terminated; "GS-9131 did not meet the targeted antiviral response"
NCT03493568
terminated; "The futility analysis on 24-week results estimated that there was only 2% probability of verifying the study hypothesis of a higher proportion pat. with no residual viremia through 48w in arm E/C/F/TAF"
NCT03532425
terminated; "Difficulties enrolling participants"
NCT03804372
terminated; "low enrollment rate"
NCT03877536
withdrawn; "Feeder cohort study closed."
14 further recorded trials
NCT03887702
terminated; "inability to accrue"
NCT03986697
withdrawn; "COVID19 emergency. No patients randomised"
NCT04059198
terminated; "Evidence of liver injury in a separate Inarigavir study"
NCT04249037
terminated; "Insufficient enrollment"
NCT04518228
terminated; "The study was closed to accrual early based on Study Monitoring Committee review indicating that the study objectives had either been achieved or could not be met within a reasonable timeframe for the then-open arms."
NCT04652700
terminated; "Voluntarily terminated due to benefit/risk assessment."
NCT04820686
terminated; "Sponsor decision"
NCT04853524
withdrawn; "Sponsor Decision"
NCT04944654
terminated; "Trial set up was delayed, funding support no longer available"
NCT05423106
terminated; "Strategic business decision, not due to safety concerns"
NCT05457530
withdrawn; "Due to No/Low enrollment"
NCT05550519
withdrawn; "Sponsor Decision after re-evaluation of strategy in the context of recruitment timelines projection"
NCT06613685
terminated; "Sponsor decision to terminate study."
NCT07115368
terminated; "Sponsor decision to terminate study."
recorded 2026-09-01 · last checked 2026-09-04
Q4
Human studies of Tenofovir alafenamide used emtricitabine 200 mg/tenofovir alafenamide 25mg — over how long?
Human studies of Tenofovir alafenamide used "emtricitabine 200 mg/tenofovir alafenamide 25mg". ClinicalTrials.gov · 2026-09-01
16 recorded entries; human; also "Genvoya 150Mg-150Mg-200Mg-10Mg Tablet", "Emtricitabine/Tenofovir Alafenamide 200 MG-25 MG Oral Tablet [DESCOVY]", "Tenofovir Alafenamide 25 mg"
Placebo to Match Emtricitabine 200mg/Tenofovir Alafenamide 25 mg.
recorded 2026-09-01 · last checked 2026-09-04
Q5
Which running trial of Tenofovir alafenamide 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
Q6
Which 30 trials of Tenofovir alafenamide posted no result?
Posted no result
30 of 30 completed trials
Registrations
NCT00036634, NCT01671787, NCT02357602, NCT02984852, NCT03092206 and NCT02904369, and 24 more
Completion dates
oldest 2003-02; newest 2024-07-25
Show the evidence
Trial
NCT00036634
2003-02
NCT01671787
2013-04
NCT02357602
2016-11
NCT02984852
2017-02
NCT03092206
2017-07-28
NCT02904369
2017-11-21
14 further recorded trials
NCT03186482
2018-01-10
NCT02486133
2018-05-31
NCT02660905
2018-06
NCT02998320
2018-09-30
NCT03646370
2019-07-24
NCT03115736
2019-12-05
NCT03502005
2019-12-30
NCT03693508
2020-05-28
NCT04551261
2021-03-12
NCT03241641
2021-03-25
NCT04009057
2022-03-21
NCT05453448
2022-05-30
NCT03122262
2022-07-29
NCT04629976
2022-12-28
Q7
At the median, Tenofovir alafenamide's trials enrolled 102 people — anything larger?
Median enrolment
102
Largest enrolment
6000
Registered trials counted
219
Q8
What do 189 spontaneous reports say about Tenofovir alafenamide — 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 alafenamide appears in spontaneous reports to regulators. Across the 10 most-reported reaction terms, 189 reaction mentions were counted: rash 67; immune reconstitution inflammatory syndrome 28; viral load increased 25; hepatocellular carcinoma 13. FAERS via Open Targets · CHEMBL2107825 · 2026-06-24
Show the evidence
rash
67
immune reconstitution inflammatory syndrome
28
viral load increased
25
hepatocellular carcinoma
13
product dispensing error
11
gastrointestinal toxicity
10
4 more recorded rows
liver transplant
10
dyspnoea
9
hepatic cancer
8
hepatitis b dna increased
8
recorded 2026-06-24 · last checked 2026-09-04
Q9
Which 10 reactions does Tenofovir alafenamide's label not list?
VEMLIDY is a substrate of P-glycoprotein (P-gp) and BCRP.
drug_interactions
Drugs that strongly affect P-gp and BCRP activity may lead to changes in VEMLIDY absorption.
drug_interactions
( 7 ) 7.1 Potential for Other Drugs to Affect VEMLIDY VEMLIDY is a substrate of P-glycoprotein (P-gp) and BCRP.
drug_interactions
Drugs that strongly affect P-gp and BCRP activity may lead to changes in tenofovir alafenamide absorption (see Table 4 ).
drug_interactions
Drugs that induce P-gp activity are expected to decrease the absorption of tenofovir alafenamide, resulting in decreased plasma concentrations of tenofovir alafenamide, which may lead to loss of therapeutic effect of VEMLIDY.
drug_interactions
Coadministration of VEMLIDY with other drugs that inhibit P-gp and BCRP may increase the absorption and plasma concentration of tenofovir alafenamide.
2 more recorded rows
Interaction statementdrug_interactions
P-gp inducer Oxcarbazepine Phenobarbital Phenytoin Antimycobacterials: ↓ tenofovir alafenamide Coadministration of VEMLIDY with rifabutin, rifampin or rifapentine is not recommended.
Interaction statementpharmacokinetics
CES1 (hepatocytes) Cathepsin A (PBMCs) CYP3A (minimal) Elimination Major route of elimination Metabolism (>80% of oral dose) t 1/2 (h) t 1/2 values refer to median terminal plasma half-life.
ChEMBL 37 — CC BY-SA 3.0 Unported · ChEMBL ATC CC BY-SA · 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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