This page shows what was measured, who it was measured in, and what that does not settle.
What Rilpivirine does in the body
Wedge something into it and the enzyme goes stiff and stops working.
Reverse transcriptase has a greasy side pocket that is not part of the machinery that does the copying. The first drug that did this, efavirenz, was rigid, so a single change to the shape of the pocket threw it out. Rilpivirine has hinges in it. When the pocket changes shape, the drug rotates and re-fits, which is why it still works against virus that efavirenz cannot touch.
Why people take it. HIV-1 infection, in people starting treatment with a lower viral load, or as maintenance therapy with cabotegravir
What happened in people
83% against 83% at week 48 in ECHO, difference -0.4 (95% CI -5.9 to 5.2), with virological failure of 13% against 6%
✎ 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 6 of 7 against 3 of 7 resistance split among long-acting failures is caused by the slow depot decline rather than by chance in 14 total events
Where it acts
HIV-1 reverse transcriptase in the cytoplasm of infected CD4-positive T cells; for the injectable form, the gluteal muscle acts as the depot
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 · 212WAX8KDD · read 2026-08-29
Its recorded molecular formula is C22H18N6∙HCl, weighing 402.88.
US prescribing information · 03880372-2c68-45c6-a53a-f420c49541d6 · read 2026-08-30
Where each sentence above came from
A person wrote this explanation into the record, with the studies named in the path below.
The recorded use, written for a reader without medical training. Not signed off.
A limit recorded against this substance. Not signed off as a reviewed claim.
The four opening statements run to 121 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.
Confirmed response below 50 copies per millilitre at week 48 by ITT-TLOVR against efavirenz
83% versus 83%, difference -0.4 (95% CI -5.9 to 5.2) against a 12% 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. Virological failure was 13% against 6%. Non-inferiority on the response endpoint and a doubled failure rate are compatible with each other, and only one of them is the headline.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Oral film-coated tablet, dispersible tablet for oral suspension, and long-acting intramuscular nanosuspension in combination with cabotegravir
Interval reported. 95% CI -5
Written into the record, not signed off as a reviewed claim.
86% versus 82%, difference 3.5% (95% CI -1.7 to 8.8), non-inferiority p<0.0001
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. No limitation is recorded for this study.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Oral film-coated tablet, dispersible tablet for oral suspension, and long-acting intramuscular nanosuspension in combination with cabotegravir
Interval reported. 95% CI -1
Written into the record, not signed off as a reviewed claim.
Confirmed viral load below 50 copies per millilitre at week 96, and virological failure by baseline viral load stratum
✓ The study showed what it set out to show
Who was studied
Pooled ECHO and THRIVE, week 96
How many people
1368
Study design
Prespecified pooled analysis of two phase 3 trials at 96 weeks
Compared against
Not recorded for this study
Kind of result
A number that stands in for health
What was found
78% versus 78% overall; responses lower and failure higher on rilpivirine above 100,000 copies per millilitre at baseline or below 95% adherence
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 stratified result became an FDA indication ceiling rather than a warning. A 12% non-inferiority margin is wide enough to contain a subgroup difference of this size.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Oral film-coated tablet, dispersible tablet for oral suspension, and long-acting intramuscular nanosuspension in combination with cabotegravir
Interval reported. Not recorded in this summary
Written into the record, not signed off as a reviewed claim.
Proportion with HIV-1 RNA at or above 50 copies per millilitre at week 48, FDA snapshot, monthly injectable cabotegravir with rilpivirine against continued oral therapy
✓ The study showed what it set out to show
Who was studied
Pooled ATLAS (NCT02951052) and FLAIR (NCT02938520), week 48
How many people
1182
Study design
Two randomised, open-label, multicentre phase 3 switch trials, pooled
Compared against
Not recorded for this study
Kind of result
A number that stands in for health
What was found
Non-inferiority met against a 4% margin for the primary and key secondary endpoints
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. Confirmed virological failure was 7 in each arm, but resistance-associated mutations were found in 6 of 7 long-acting failures against 3 of 7 on oral therapy. Injection site reactions occurred in 83% of long-acting recipients.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Oral film-coated tablet, dispersible tablet for oral suspension, and long-acting intramuscular nanosuspension in combination with cabotegravir
Interval reported. Not recorded in this summary
Written into the record, not signed off as a reviewed claim.
RNAWiki holds 4 written-up human studies for this substance, each with the question it asked.
How we know it
Each card names the study, the number of people and what the study set out to measure.
What this does not prove
These summaries were written by a person and have not been signed off as reviewed claims.
Why it matters
A study that failed is as informative as one that worked, and both are here.
What we still do not know
No reviewed claim exists, so no exact population, effect size or interval is published yet.
What it changes in the body◇Read from sources, not yet reviewed
The path through the body
From what a person takes to what changes. A solid line is a step measured in people. A dashed line is a step nobody has measured that way.
Start
Rilpivirine
What a person takes: Oral film-coated tablet, dispersible tablet for oral suspension, and long-acting intramuscular nanosuspension in combination with cabotegravir.
The measurement behind this step
The oral form must be taken with a meal, because dissolution is pH-dependent and exposure falls materially without food. The injectable form is given into the gluteal muscle alongside cabotegravir, after an oral lead-in period used to confirm tolerability before a month of drug is committed to a depot that cannot be withdrawn.
Getting in
Swallowed with a meal, because without one it barely dissolves
The tablet has to be taken with food, and not as a suggestion. On an empty stomach, or with a drug that reduces stomach acid, enough less of it is absorbed that the virus can escape.
╌╌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
Rilpivirine is highly lipophilic and its dissolution is pH-dependent, requiring gastric acidity. Exposure falls substantially when taken without food or alongside acid-suppressing agents, which is why proton pump inhibitors are contraindicated outright rather than flagged, and why H2 antagonists carry a timing separation on the label. The same lipophilicity and low aqueous solubility are exactly what make a month-long intramuscular depot possible.
Or injected into muscle, where it sits and releases for a month
The other form is a suspension of drug crystals injected into the buttock. The crystals dissolve slowly, releasing drug for a month or two, which is why an injection can replace daily tablets.
╌╌Described, with no measurement named. No measurement is named for this step, so it is drawn as an unconfirmed link.
The measurement behind this step
The long-acting form is a nanocrystal suspension stabilised with a poloxamer, injected intramuscularly, where dissolution rate is set by particle surface area. Release continues for months after the last injection, giving a pharmacokinetic tail that is the therapeutic benefit and the principal risk in the same property: drug concentrations decline through the subtherapeutic range slowly rather than abruptly.
It enters cells and wedges into the pocket beside the copying machinery
Inside the cell the drug slots into the same greasy side pocket that efavirenz uses, next to but not inside the part of the enzyme that does the chemistry.
──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
Rilpivirine binds the non-nucleoside pocket in the p66 subunit of reverse transcriptase, roughly 10 angstroms from the polymerase catalytic site, and inhibits allosterically rather than competing with the nucleotide substrate. Plasma protein binding exceeds 99%, principally to albumin.
When the pocket changes shape, the drug rotates instead of falling out
This is what makes it different from the drug before it. Rilpivirine has two hinges. If a mutation reshapes the pocket, the molecule turns and finds a new fit rather than losing its grip.
╌╌Described, with no measurement named. No measurement is named for this step, so it is drawn as an unconfirmed link.
The measurement behind this step
The two rotatable bonds flanking the central pyrimidine allow multiple bound conformations, so substitutions such as K103N that abolish efavirenz binding leave rilpivirine active. Compensation has limits: E138K and K101E change the pocket in ways rotation does not accommodate, and E138K additionally reduces susceptibility to emtricitabine and lamivudine, so it reaches beyond its own class.
The enzyme stalls, and suppression holds unless the starting viral load was high
Copying stops and viral load falls. It stays down in about four out of five people at two years, but a person who started with a very high viral load is measurably more likely to be in the fifth.
╌╌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
Pooled 96-week suppression was 78% for rilpivirine and 78% for efavirenz. Within the population with baseline viral load at or below 100,000 copies per millilitre, week 96 suppression was 84% against 81% with virological failure of 5.9% against 2.4%. Above that threshold both response and failure moved against rilpivirine, which is why the FDA indication stops there. Most virological failures occurred in the first 48 weeks.
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 starting treatment with a viral load at or below 100,000 copies per millilitre, and virologically suppressed people who have switched to monthly or two-monthly injections of cabotegravir and rilpivirine.
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: “Trial TMC278HTX2002 The safety, tolerability, antiviral activity and pharmacokinetics of EDURANT and EDURANT PED weight-adjusted doses 25, 15 and 12.5 mg daily was evaluated in a single-arm, open-label Phase 2 trial in 26 HIV-1 infected pediatric subjects 2 to less than 12 years of age and weighing at least 16 kg.”
US prescribing information · 03880372-2c68-45c6-a53a-f420c49541d6 · read 2026-08-30
On older people, the label states: “Clinical studies of EDURANT did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects.”
US prescribing information · 03880372-2c68-45c6-a53a-f420c49541d6 · read 2026-08-30
On people who are pregnant, the label states: “Rilpivirine in combination with a background regimen was evaluated in a clinical trial of 19 HIV-1 infected pregnant women during the second and third trimesters and postpartum.”
US prescribing information · 03880372-2c68-45c6-a53a-f420c49541d6 · read 2026-08-30
On people who are breastfeeding, the label states: “Risk Summary Based on limited data after oral administration, rilpivirine is present in human breast milk.”
US prescribing information · 03880372-2c68-45c6-a53a-f420c49541d6 · read 2026-08-30
On people with reduced liver function, the label states: “No dosage adjustment of EDURANT or EDURANT PED is required in patients with mild (Child-Pugh Class A) or moderate (Child-Pugh Class B) hepatic impairment.”
US prescribing information · 03880372-2c68-45c6-a53a-f420c49541d6 · read 2026-08-30
On people with reduced kidney function, the label states: “No dose adjustment of EDURANT or EDURANT PED is required in patients with mild or moderate renal impairment.”
US prescribing information · 03880372-2c68-45c6-a53a-f420c49541d6 · read 2026-08-30
Where the result stopped carrying
The registration programme met non-inferiority overall while performing measurably worse above 100,000 copies per millilitre at baseline, and the FDA wrote that ceiling into the indication rather than into a warning
Proton pump inhibitors, one of the most widely prescribed drug classes in the world, had to be made an outright contraindication because of loss of virological response and possible class resistance
This is a scope explorer, not a diagnosis engine.
It shows who was studied so you can see whether people similar to you were included.
RNAWiki cannot tell whether a study fits you. It can show who was in it.
What it would be like to take◇Read from sources, not yet reviewed
Why it might seem to do nothing
A real effect and a noticed effect are different things. These are the recorded reasons the two come apart.
It was studied in different people
The people in the studies were not much like the reader.
On this record: Which groups were under-represented in the studies has not been recorded for this substance. Pregnancy, breastfeeding, children, older adults, and people with liver or kidney conditions are commonly excluded from trials; nothing here says whether they were.
There was nothing to correct
Where a level is already normal, topping it up may change nothing.
On this record: Positioned in guidelines as an alternative rather than a preferred first-line agent, principally because of the baseline viral load ceiling and the interaction profile
The evidence may simply be wrong
Small early studies often do not hold up.
On this record: RNAWiki has not yet published a reviewed conclusion for this use.
Other reasons RNAWiki checked and found nothing for (10)
It was studied for a different goal
The studies measured something else entirely. Nothing in this record points to this reason.
A different form was studied
The studied form is not the form on the shelf. Nothing in this record points to this reason.
Something else had to happen too
In the studies it was paired with training, a diet or another treatment. Nothing in this record points to this reason.
The change is too small to feel
A real change can still sit below what a person notices. Nothing in this record points to this reason.
Day-to-day swing hides it
Sleep, food, stress and time of day move most numbers more than this would. Nothing in this record points to this reason.
Not enough time yet
The studies ran longer than the person has waited. Nothing in this record points to this reason.
It was not taken as studied
Missed days change the result, and studies count them. Nothing in this record points to this reason.
Something else changed at the same time
Two changes at once cannot be told apart afterwards. Nothing in this record points to this reason.
The product may not be what it says
Contents of a sold product are not always what the label states. Nothing in this record points to this reason.
No recorded reason
RNAWiki has nothing stored that would explain it. Nothing in this record points to this reason.
None of these is a reason to take more. Taking more is not a step this page ever suggests.
What it would be like to take◇Read from sources, not yet reviewed
What taking it involves
The recorded facts about getting hold of it and using it. Nothing here is a suggestion about what you should do.
How it is supplied
Given by a clinician
❝ Quoted from a source
Where this came from
Copied from a source RNAWiki stored, with the source named.
Read from the recorded approval status.
No source is stored against this line.
Form and route
Oral film-coated tablet, dispersible tablet for oral suspension, and long-acting intramuscular nanosuspension in combination with cabotegravir
✎ 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
The oral form must be taken with a meal, because dissolution is pH-dependent and exposure falls materially without food.
✎ Source-linked record
Where this came from
A person wrote this into the record with the study named beside it. No reviewer has signed it off.
Recorded notes on how this is sold. The rest of the recorded wording: The injectable form is given into the gluteal muscle alongside cabotegravir, after an oral lead-in period used to confirm tolerability before a month of drug is committed to a depot that cannot be withdrawn.
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
Depressive disorders including suicidal ideation are labelled, as are hepatotoxicity and rash, though all occurred less often than on efavirenz in the registration trials. QT interval prolongation occurs at supratherapeutic exposure. For the injectable form, injection site reactions affected 83% of recipients in the pooled phase 3 analysis and were the commonest reason for withdrawal from it. The interaction profile is the practical risk: all proton pump inhibitors, rifampin, rifapentine, four anticonvulsants, multi-dose systemic dexamethasone and St John wort are contraindicated because losing exposure means losing virological control and possibly the class.
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, dispersible tablet for oral suspension, and long-acting intramuscular nanosuspension in combination with cabotegravir
✎ Source-linked record
Where this came from
A person wrote this into the record with the study named beside it. No reviewer has signed it off.
The form used in the studies cited on this page.
No source is stored against this line.
What is sold
A recorded note compares this form with the others that are sold. It is kept below, word for word.
§ A fixed RNAWiki sentence
Where this came from
Wording RNAWiki always uses, not a finding about this substance.
The recorded note, unchanged: The injectable form is given into the gluteal muscle alongside cabotegravir, after an oral lead-in period used to confirm tolerability before a month of drug is committed to a depot that cannot be withdrawn.
No source is stored against this line.
What is recorded as being sold
30 products list this as an active ingredient in the United States drug directory. 20 of them contain it and nothing else.
FDA National Drug Code directory · 11712-823 · read 2026-08-29
They are sold as injection, suspension, powder, tablet, tablet, film coated and tablet, for suspension, taken oral.
FDA National Drug Code directory · 11712-823 · read 2026-08-29
The regulator's established pharmacologic class for it is human immunodeficiency virus 1 non-nucleoside analog reverse transcriptase inhibitor [epc], non-nucleoside analog [ext] and non-nucleoside reverse transcriptase inhibitors [moa].
FDA National Drug Code directory · 11712-823 · read 2026-08-29
8 published labels name it as an active ingredient. 3 of them describe this substance alone, which is where its own label text on this page comes from.
US prescribing information · 806653d1-bf35-4924-b999-ad5d21821cc1 · read 2026-08-29
Those labels are classed as human prescription drug.
US prescribing information · 806653d1-bf35-4924-b999-ad5d21821cc1 · read 2026-08-29
EDURANT is oral at 3 DOSAGE FORMS AND STRENGTHS EDURANT: 25 mg tablets ( 3 ) EDURANT PED: 2.5 mg tablets for oral suspension ( 3 ) EDURANT 25 mg Film-Coated Tablets 25 mg white to off-white, film-coated, round, biconvex, tablet of 6.4 mm,…, recorded as fda label in effect 2025-08-28 in the United States.
US prescribing information · 03880372-2c68-45c6-a53a-f420c49541d6 · 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.
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 Rilpivirine 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 6 of 7 against 3 of 7 resistance split among long-acting failures is caused by the slow depot decline rather than by chance in 14 total events
Why it sounds right. It follows from something real on this page: a body step, an animal result or a related finding.
The missing step. Nobody measured this in people for this use, or the study that did measure it did not show it.
What would change this
A study in people, for this exact use, measuring this exact thing, that a reviewer signs off.
RNAWiki has not yet published a reviewed conclusion for this use.
✗Goes past the evidence
That a rilpivirine failure costs more future options than an efavirenz failure because E138K reaches the nucleoside backbone — mechanistically clear and never tested as an endpoint
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 non-inferiority on the response endpoint means equivalence, when the same trials reported roughly double the virological failure rate
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 Rilpivirine 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.
ECHO: 83% against 83%, with twice the virological failure and half the side effects
In plain words
Against efavirenz with the same nucleoside backbone, rilpivirine matched it exactly at 48 weeks. Underneath that tie, it failed virologically about twice as often and caused about half as many moderate-to-severe side effects.
What was measured
Confirmed response below 50 copies per millilitre at week 48, ITT-TLOVR; difference -0.4 (95% CI -5.9 to 5.2)
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
ECHO (NCT00540449) randomised 690 treatment-naive adults at 112 sites in 21 countries, double-blind and double-dummy, to rilpivirine 25 mg or efavirenz 600 mg once daily, each with tenofovir disoproxil fumarate and emtricitabine. At week 48, 287 of 346 (83%) and 285 of 344 (83%) had a confirmed response below 50 copies per millilitre by the intention-to-treat time-to-loss-of-virological-response algorithm; the logistic regression point estimate for the difference was -0.4 (95% CI -5.9 to 5.2) against a 12% non-inferiority margin. Virological failure was 13% against 6% (11% against 4% by the same algorithm). Grade 2 to 4 adverse events occurred in 55 (16%) against 108 (31%), p<0.0001, and discontinuation for adverse events in 8 (2%) against 27 (8%). Plasma lipid increases were significantly lower on rilpivirine.
Written into the record, not signed off as a reviewed claim
THRIVE: 86% against 82% across three different nucleoside backbones
In plain words
The companion trial let investigators pick the two background drugs rather than fixing them, which tests whether the result depends on what it is combined with. It did not: 86% against 82%, and the same halving of moderate-to-severe side effects.
What was measured
Confirmed response below 50 copies per millilitre at week 48, ITT-TLOVR; difference 3.5% (95% CI -1.7 to 8.8)
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
THRIVE (NCT00543725) randomised 680 treatment-naive adults at 98 centres in 21 countries, double-blind and double-dummy, to rilpivirine 25 mg or efavirenz 600 mg with an investigator-selected background of tenofovir disoproxil-emtricitabine, zidovudine-lamivudine or abacavir-lamivudine. At week 48, 291 of 340 (86%) against 276 of 338 (82%) responded by ITT-TLOVR, difference 3.5% (95% CI -1.7 to 8.8), non-inferiority p<0.0001 against a 12% margin. Virological failure was 24 of 340 (7%) against 18 of 338 (5%). Discontinuation for adverse events was 15 (4%) against 25 (7%), and grade 2 to 4 treatment-related adverse events 54 (16%) against 104 (31%), p<0.0001, with rash, dizziness and lipid increases all significantly lower on rilpivirine.
Written into the record, not signed off as a reviewed claim
The non-inferiority result concealed a subgroup, and the FDA put it in the indication
In plain words
Overall the two drugs tied at 78% at two years. In people whose viral load was above 100,000 copies per millilitre when they started, rilpivirine did worse and failed more often. The FDA did not deal with that in a warning: it wrote the ceiling into what the drug is approved for.
What was measured
Virological failure by baseline viral load stratum, and the resulting FDA indication ceiling of 100,000 copies per millilitre
Effect estimate
No reviewed effect estimate exists for this record.
Limits
This entry records a failure.
From the source
The pooled 96-week analysis of ECHO and THRIVE covered 1,368 patients and found response rates of 78% in both groups. Responses were similar across background regimen, sex and race, and in patients with more than 95% adherence or a baseline viral load at or below 100,000 copies per millilitre. Responses were lower and virological failure higher for rilpivirine in patients with 95% or less adherence, or with a baseline viral load above 100,000 copies per millilitre. In the restricted subgroup at or below 100,000 copies per millilitre, 543 patients gave 84% against 81% at week 96 with virological failure of 5.9% against 2.4%. The Edurant prescribing information carries the consequence in section 1.1: the treatment-naive indication is limited to patients with HIV-1 RNA at or below 100,000 copies per millilitre, with a Limitations of Use statement that more treated subjects above that threshold experienced virological failure. A non-inferiority margin of 12% is wide enough to absorb a real subgroup difference, and this is what it looks like when it does.
Written into the record, not signed off as a reviewed claim
ATLAS and FLAIR: monthly injections held suppression in 1,182 people
In plain words
Two trials switched already-suppressed patients from daily tablets to a monthly injection of cabotegravir and rilpivirine. It worked as well as staying on tablets, with the same small number of failures in each arm. Eighty-three per cent of injection recipients had a reaction at the injection site.
What was measured
Proportion with HIV-1 RNA at or above 50 copies per millilitre at week 48, FDA snapshot, against a 4% non-inferiority margin
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
ATLAS (NCT02951052) and FLAIR (NCT02938520) were randomised, open-label, multinational phase 3 trials in adults with plasma HIV-1 RNA below 50 copies per millilitre, randomised 1:1 to continue current therapy or switch to monthly intramuscular cabotegravir with rilpivirine after a four-week oral lead-in. The pooled intention-to-treat exposed population was 591 per arm, 28% women by sex at birth and 19% aged 50 or over. Non-inferiority was met at week 48 for the primary endpoint of HIV-1 RNA at or above 50 copies per millilitre by FDA snapshot, against a 4% margin, and for the key secondary endpoint below 50 copies per millilitre. Seven participants in each arm (1.2%) had confirmed virological failure, defined as two consecutive measurements at or above 200 copies per millilitre. Injection site reactions occurred in 83% of long-acting recipients, decreased in incidence over time, and led to withdrawal of 6 participants (1%). Serious adverse events were 4% in each arm.
Written into the record, not signed off as a reviewed claim
Same number of failures, different consequences: 6 of 7 carried resistance
In plain words
The injection and the tablets failed equally rarely. But of the seven failures on injections, six had developed resistance mutations, against three of seven on tablets. When a drug takes months to leave the body, failure is not a moment; it is a long stretch of too little drug.
What was measured
That the higher proportion of resistance among long-acting failures is caused by the slow decline of drug from the intramuscular depot — mechanistically coherent, and resting on 6 events against 3
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
In the pooled ATLAS and FLAIR analysis, confirmed virological failure occurred in 7 of 591 in each arm. Resistance-associated mutations were found in 6 of 7 long-acting failures against 3 of 7 on continued oral therapy. The mechanism is pharmacokinetic rather than virological: rilpivirine released from an intramuscular nanosuspension declines over months rather than days, so a person who stops attending for injections, or who fails for any reason, spends an extended period with drug concentrations below the level that suppresses virus and above the level that selects for resistance. This is the property the oral lead-in and the resistance-history exclusions in the label exist to manage. The count of 6 against 3 is measured. That this reflects the long pharmacokinetic tail rather than chance in a total of 14 events is an inference, well grounded mechanistically and made on small numbers.
Written into the record, not signed off as a reviewed claim
A stomach acid drug can end it, and that is a contraindication rather than a caution
In plain words
Rilpivirine only dissolves in an acidic stomach. Proton pump inhibitors, among the most widely used drugs in the world, raise stomach pH enough that rilpivirine absorption falls far enough to lose control of the virus. The label lists them as contraindicated, not as an interaction to watch.
What was measured
Labelled contraindication with all proton pump inhibitors and seven CYP3A inducers, on the ground of loss of virological response and possible class resistance
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
The Edurant prescribing information contraindicates co-administration with all proton pump inhibitors named as a class, on the stated ground that significant decreases in rilpivirine plasma concentration may occur through gastric pH increase, and that this may result in loss of virological response and possible resistance to rilpivirine or to the non-nucleoside class. The same contraindication table covers the CYP3A inducers carbamazepine, oxcarbazepine, phenobarbital, phenytoin, rifampin, rifapentine, more than single-dose systemic dexamethasone, and St John wort. Rilpivirine is also the rare antiretroviral whose absorption requires a meal rather than merely being improved by one. The audit point is not that an interaction exists but that the class of drug most likely to be taken alongside it without either party thinking about it is the class that ends it.
Written into the record, not signed off as a reviewed claim
The flexibility that beats K103N does not beat E138K, and that is the trade
In plain words
Rilpivirine was designed to bend so that mutations which throw efavirenz out cannot throw it out. That worked. But it created its own mutations, and one of them is selected by the very drug most often paired with it.
What was measured
That a virological failure on rilpivirine costs more future options than a failure on efavirenz, because E138K reaches the nucleoside backbone as well as the non-nucleoside
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
The diarylpyrimidine scaffold retains activity against K103N, the substitution that ends efavirenz and nevirapine, because it can rotate into an alternative bound conformation. Its own resistance pathway runs principally through E138K and K101E. E138K is the point that is easy to miss: it also reduces susceptibility to emtricitabine and lamivudine, so a rilpivirine failure with E138K can compromise the nucleoside backbone it was taken with rather than only the non-nucleoside. The pooled 96-week analysis reports that rilpivirine resistance-associated mutations beyond week 48 were consistent with those observed in year 1, and that the majority of virological failures occurred within the first 48 weeks. What is measured is the mutation pattern at failure. What is inferred, and is the reason the drug is positioned where it is, is that the net resistance cost of a rilpivirine failure is higher than the class-level cost of an efavirenz failure, which no trial has compared head to head as an endpoint.
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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 second-generation non-nucleoside inhibitor flexible enough to keep binding reverse transcriptase through the mutations that defeat efavirenz; it matched efavirenz at 78% suppressed at 96 weeks with half the grade 2 to 4 adverse events, but failed virologically more often, and specifically enough above 100,000 copies per millilitre that the FDA restricted the indication below that line.
Recorded evidence blocks (10)
Q1
On the Rilpivirine label: indicated for what?
"Rilpivirine tablets are a human immunodeficiency virus type 1 (HIV-1) specific, non-nucleoside reverse transcriptase inhibitor (NNRTI) indicated in combination with other antiretroviral agents for the treatment of HIV-1 infection in treatment-naïve patients 12 years of age and older and weighing at least 35 kg with…": indications and usage on Rilpivirine's label. DailyMed label · dadbf50d-6b7d-4fb5-bd9f-7769b048e764 · 2026-07-15
Q2
74 registered trials of Rilpivirine — at which phases?
5 of Rilpivirine's trials stopped: safety, accrual/recruitment, funding/business, other?
safety (1), accrual/recruitment (1), funding/business (1) and other (2): Rilpivirine's stop wording, clustered. CLINICALTRIALS_SNAPSHOT · 2026-09-01
"Strategic decision"; 5 of 74 registered studies
Show the evidence
Trial
NCT00741741
terminated; "Strategic decision"
NCT01049932
terminated; "Trial closed due to additional safety information."
NCT01692470
withdrawn; "The company decided to cancel this study in conformity with Philippines FDA Circular 2013-004"
NCT02470650
withdrawn; "No participants enrolled"
NCT03563742
terminated; "High SF rate (less treatment-naïve subjects \& subjects with viral load \<100000). Reevaluation in scientific position in India after internal discussion."
recorded 2026-09-01 · last checked 2026-09-04
Q4
Human studies of Rilpivirine used TMC278 25 mg — over how long?
Human studies of Rilpivirine used "TMC278 25 mg". ClinicalTrials.gov · 2026-09-01
7 recorded entries; human; also "TMC278 75 mg", "TMC278 150 mg", "Rilpivirine 25 mg"
50 hours; Elimination The terminal elimination half-life of rilpivirine is approximately 50 hours.
tmaxpharmacokinetics
0 h; Table 8: Pharmacokinetic Results of Total Rilpivirine After Administration of Rilpivirine 25 mg Once Daily as Part of an Antiretroviral Regimen, During the 2 nd Trimester of Pregnancy, the 3 rd Trimester of Pregnancy and Postpartum Pharmacokinetics of total rilpivirine (mean ± SD, t max : median [range]) Postpartum (6 to 12 Weeks) (n=11) 2 nd Trimester of pregnancy (n=15) 3 rd Trimester of…
metabolismpharmacokinetics
Metabolism In vitro experiments indicate that rilpivirine primarily undergoes oxidative metabolism mediated by the cytochrome P450 (CYP) 3A system .
recorded 2026-07-15 · last checked 2026-09-04
Q6
Which 29 trials of Rilpivirine posted no result?
Posted no result
29 of 29 completed trials
Registrations
NCT00739622, NCT00812292, NCT00744770, NCT00736905, NCT01268839 and NCT01205139, and 23 more
Completion dates
oldest 2008-12; newest 2024-05-23
Show the evidence
Trial
NCT00739622
2008-12
NCT00812292
2009-04
NCT00744770
2009-06
NCT00736905
2009-11
NCT01268839
2010-05
NCT01205139
2011-03
14 further recorded trials
NCT01288755
2011-05
NCT01467531
2012-02
NCT01519128
2012-04
NCT01615614
2012-09
NCT01719614
2013-01
NCT01804244
2013-03
NCT01796431
2013-07
NCT01715636
2014-07
NCT01656018
2016-01
NCT02157311
2016-01
NCT02561936
2016-04
NCT02547870
2016-04-26
NCT02547844
2016-10
NCT02529059
2017-05
Q7
At the median, Rilpivirine's trials enrolled 58 people — anything larger?
Median enrolment
58
Largest enrolment
1578
Registered trials counted
74
Q8
What do 750 spontaneous reports say about Rilpivirine — 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.
Rilpivirine appears in spontaneous reports to regulators. Across the 10 most-reported reaction terms, 750 reaction mentions were counted: virologic failure 124; viral load increased 92; drug resistance 86; product use in unapproved therapeutic environment 80. FAERS via Open Targets · CHEMBL1628504 · 2026-06-24
Show the evidence
virologic failure
124
viral load increased
92
drug resistance
86
product use in unapproved therapeutic environment
80
treatment failure
80
pathogen resistance
76
4 more recorded rows
product dose omission issue
73
blood hiv rna increased
64
viral mutation identified
54
dyspnoea
21
recorded 2026-06-24 · last checked 2026-09-04
Q9
Which 10 reactions does Rilpivirine's label not list?
Rilpivirine is primarily metabolized by cytochrome P450 (CYP)3A, and drugs that induce or inhibit CYP3A may thus affect the clearance of rilpivirine.
drug_interactions
Coadministration of rilpivirine and drugs that induce CYP3A may result in decreased plasma concentrations of rilpivirine and loss of virologic response and possible resistance to rilpivirine or to the class of NNRTIs.
drug_interactions
Coadministration of rilpivirine and drugs that inhibit CYP3A may result in increased plasma concentrations of rilpivirine.
drug_interactions
Antimycobacterials: rifabutin * ↓ rilpivirine Concomitant use of rilpivirine with rifabutin may cause a decrease in the plasma concentrations of rilpivirine (induction of CYP3A enzymes).
drug_interactions
Azole Antifungal Agents: fluconazole itraconazole ketoconazole *† posaconazole voriconazole ↑ rilpivirine ↓ ketoconazole Concomitant use of rilpivirine with azole antifungal agents may cause an increase in the plasma concentrations of rilpivirine (inhibition of CYP3A enzymes).
drug_interactions
HIV-Antiviral Agents: Protease Inhibitors (PIs)-Boosted (i.e., with coadministration of low-dose ritonavir) or Unboosted (i.e., without coadministration of low-dose ritonavir) darunavir/ritonavir *† ↑ rilpivirine ↔ boosted darunavir Concomitant use of rilpivirine with darunavir/ritonavir may cause an increase in the plasma concentrations of rilpivirine (inhibition of CYP3A enzymes).
2 more recorded rows
Interaction statementdrug_interactions
Lopinavir/ritonavir *† ↑ rilpivirine ↔ boosted lopinavir Concomitant use of rilpivirine with lopinavir/ritonavir may cause an increase in the plasma concentrations of rilpivirine (inhibition of CYP3A enzymes).
Interaction statementdrug_interactions
Other boosted PIs (atazanavir/ritonavir, fosamprenavir/ritonavir, saquinavir/ritonavir, tipranavir/ritonavir) ↑ rilpivirine ↔ boosted PI Concomitant use of rilpivirine with boosted PIs may cause an increase in the plasma concentrations of rilpivirine (inhibition of CYP3A enzymes).
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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