This page shows what was measured, who it was measured in, and what that does not settle.
What Darunavir does in the body
HIV-1 infection, as part of a combination regimen
HIV makes its proteins as one long strand and then uses molecular scissors to cut them into working parts. Darunavir jams the scissors. What makes it different from earlier drugs of its kind is where it grips: it holds onto the fixed skeleton of the enzyme rather than the parts that stick out. Mutations change the parts that stick out. They cannot easily change the skeleton without breaking the enzyme, so the virus has to accumulate many changes rather than one, and it usually cannot.
What happened in people
61% against 15% responding in heavily treatment-experienced patients, difference 46% (95% CI 35 to 57), adjusted odds ratio 11.72
✎ 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 cumulative darunavir exposure causes cardiovascular disease — a dose-dependent observational association with an internal null comparator, no mechanism and no randomised test
Where it acts
HIV-1 protease, acting in the budding virion at the plasma membrane of an infected cell rather than inside the cell it will go on to infect
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
Its recorded molecular formula is C27H37N3O7S, weighing 547.67.
US prescribing information · 49606d5e-f45f-45eb-9ab8-15aa6a233875 · 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 115 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 a viral load reduction of at least 1 log10 copies per millilitre from baseline at week 48 in treatment-experienced patients
✓ The study showed what it set out to show
Who was studied
POWER 1 and 2 (TMC114-C213, TMC114-C202, NCT00071097)
How many people
230
Study design
Phase IIB, randomised, pooled subgroup analysis at week 48
Compared against
Not recorded for this study
Kind of result
A number that stands in for health
What was found
61% versus 15%, difference 46% (95% CI 35 to 57), p<0.0001; adjusted odds ratio 11.72 (95% CI 5.75 to 23.89)
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 and oral suspension, always with a pharmacokinetic booster
Interval reported. 95% CI 35 to 57), p<0
Written into the record, not signed off as a reviewed claim.
77% versus 68%, estimated difference 9% (95% CI 2 to 16)
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 more consequential secondary result is the resistance count: primary protease mutations in 6 darunavir failures against 20 on lopinavir, and nucleoside mutations in 4 against 15.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Oral film-coated tablet and oral suspension, always with a pharmacokinetic booster
Interval reported. 95% CI 2 to 16)
Written into the record, not signed off as a reviewed claim.
Proportion with HIV-1 RNA below 50 copies per millilitre at week 48, per-protocol time-to-loss-of-virological-response, in treatment-naive patients
✓ The study showed what it set out to show
Who was studied
ARTEMIS (TMC114-C211, NCT00258557)
How many people
689
Study design
Phase 3, randomised, open-label, non-inferiority, 48-week primary with 192-week design
Compared against
Not recorded for this study
Kind of result
A number that stands in for health
What was found
84% versus 78%, estimated difference 5.6% (95% CI -0.1 to 11), p<0.001 for non-inferiority; 79% versus 67% above 100,000 copies per millilitre at baseline (p<0.05)
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 and oral suspension, always with a pharmacokinetic booster
Interval reported. 95% CI -0
Written into the record, not signed off as a reviewed claim.
Loss of future drug options, defined as new intermediate or high level resistance to a drug the virus was sensitive to at entry, protease inhibitor monotherapy against continued triple therapy
✓ The study showed what it set out to show
Who was studied
PIVOT (ISRCTN04857074)
How many people
587
Study design
Randomised, controlled, open-label pragmatic strategy trial, median 100-month follow-up
Compared against
Not recorded for this study
Kind of result
A number that stands in for health
What was found
Cumulative eight-year risk 2.1% versus 2.7%, difference -0.6% (95% CI -3.2 to 2.0)
Repeated elsewhere
Partially Replicated
What this does not prove. Meeting one endpoint in one population does not carry to other goals or other people.
The limits of this study, and where it came from
Main limit. Serious clinical events occurred in 23 of 296 (7.8%) monotherapy participants against 12 of 291 (4.1%) on triple therapy, p=0.08. The authors state that a small excess risk cannot be excluded, and monotherapy is not a recommended strategy.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Oral film-coated tablet and oral suspension, always with a pharmacokinetic booster
Interval reported. 95% CI -3
Written into the record, not signed off as a reviewed claim.
Incidence of centrally validated cardiovascular disease by cumulative exposure to ritonavir-boosted darunavir and to ritonavir-boosted atazanavir
✗ The study did not show it
Who was studied
D:A:D contemporary protease inhibitor analysis
How many people
35711
Study design
Prospective observational multicohort study, 11 cohorts, median 6.96 years
Compared against
Not recorded for this study
Kind of result
A number that stands in for health
What was found
Adjusted incidence rate ratio 1.59 (95% CI 1.33 to 1.91) per five years of darunavir-ritonavir; 1.03 (0.90 to 1.18) for atazanavir-ritonavir
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. This row records a harm signal, not a failed efficacy endpoint. Incidence rose from 4.91 to 13.67 events per 1,000 person-years across exposure strata. The study is observational and no mechanism has been established.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Oral film-coated tablet and oral suspension, always with a pharmacokinetic booster
Interval reported. 95% CI 1
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
Darunavir
What a person takes: Oral film-coated tablet and oral suspension, always with a pharmacokinetic booster.
The measurement behind this step
Taken with food, always with ritonavir or cobicistat. The booster requirement is not a convenience: unboosted exposure is too low to be therapeutic, and the label has no unboosted regimen. Absorption is substantially reduced without food.
Getting in
Swallowed with food, and never on its own
Taken with a meal, and always with a second small drug whose only purpose is to stop the liver clearing it. Without that partner it disappears too fast to work.
╌╌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
Darunavir is a CYP3A4 substrate with low bioavailability unboosted, so it is co-administered with ritonavir or cobicistat, potent CYP3A inhibitors that raise its exposure severalfold. Food increases absorption substantially. The booster is what makes the regimen work and is also the source of nearly every clinically important interaction attributed to the drug.
The drug diffuses into infected cells. Unlike the drugs that stop the virus getting established, this one works at the end of the cycle, where new virus particles are being packaged to leave.
╌╌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
Darunavir is passively permeable and highly protein-bound, principally to alpha-1-acid glycoprotein. Its site of action is the maturation step: HIV-1 protease cleaves the Gag and Gag-Pol polyproteins during and after budding, so the drug acts on virions leaving an already-infected cell rather than protecting an uninfected one.
It grips the fixed skeleton of the enzyme, not the parts that can change
Older protease inhibitors held onto side groups that stick out of the enzyme. Mutations change those. Darunavir hydrogen-bonds to the enzyme backbone instead, which the virus cannot alter without destroying the enzyme.
╌╌Described, with no measurement named. No measurement is named for this step, so it is drawn as an unconfirmed link.
The measurement behind this step
The bis-tetrahydrofuranyl group makes hydrogen bonds to the main-chain amide nitrogen and carbonyl oxygen of aspartate 29 and aspartate 30 in the S2 subsite. Backbone conformation in the active site is essentially invariant across resistant clinical isolates, because the fold depends on it. Binding affinity is picomolar, roughly two orders of magnitude tighter than first-generation inhibitors, and darunavir additionally inhibits dimerisation of the protease monomers, a mechanism the rest of the class lacks.
The polyprotein is never cut, so the particle assembles wrong
New virus particles still form and still leave the cell. But the long protein chain inside them is never cut into working parts, so the particle is structurally immature and cannot infect anything.
╌╌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
Gag and Gag-Pol remain uncleaved, so the conical capsid never forms and the virion is non-infectious. Escape requires accumulating multiple substitutions in protease, each of which costs catalytic efficiency, which is the origin of the high genetic barrier. The alternative escape route runs through the Gag cleavage sites themselves: T375A at p2/p7 confers roughly ten-fold resistance while leaving the protease sequence unchanged.
Virus falls, and failure usually costs nothing for next time
Suppression rates match or beat the older drugs of the class. The distinctive result is what happens when it does not work: most people who fail on darunavir have a virus that is still fully susceptible to it and to every other drug in the class.
╌╌Described, with no measurement named. No measurement is named for this step, so it is drawn as an unconfirmed link.
The measurement behind this step
In ARTEMIS at 96 weeks, no major protease resistance mutation developed in any virological failure with paired genotypes in either arm, and all such failures remained phenotypically susceptible to all protease inhibitors. In TITAN, primary protease mutations appeared in 21% of darunavir failures against 36% of lopinavir failures. In PIVOT, eight years of protease inhibitor monotherapy produced a 2.1% cumulative risk of losing a future drug option.
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 with multidrug-resistant HIV-1, people who have failed earlier protease inhibitors, and, less often now, people starting treatment in whom an integrase inhibitor is not appropriate.
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: “The safety, pharmacokinetic profile, and virologic and immunologic responses of darunavir/ritonavir administered twice daily were evaluated in treatment-experienced HIV-1-infected pediatric subjects 3 to less than 18 years of age and weighting at least 10 kg.”
US prescribing information · 49606d5e-f45f-45eb-9ab8-15aa6a233875 · read 2026-08-30
On older people, the label states: “Clinical studies of darunavir did not include sufficient numbers of patients aged 65 years and over to determine whether they respond differently from younger patients.”
US prescribing information · 49606d5e-f45f-45eb-9ab8-15aa6a233875 · read 2026-08-30
On people who are pregnant, the label states: “Data Human Data Darunavir/ritonavir (600/100 mg twice daily or 800/100 mg once daily) in combination with a background regimen was evaluated in a clinical trial of 36 pregnant women during the second and third trimesters, and postpartum.”
US prescribing information · 49606d5e-f45f-45eb-9ab8-15aa6a233875 · read 2026-08-30
On people who are breastfeeding, the label states: “Risk Summary The Centers for Disease Control and Prevention recommend that HIV-infected mothers not breastfeed their infants to avoid risking postnatal transmission of HIV.”
US prescribing information · 49606d5e-f45f-45eb-9ab8-15aa6a233875 · read 2026-08-30
On people with reduced liver function, the label states: “No dosage adjustment of darunavir/ritonavir is necessary for patients with either mild or moderate hepatic impairment.”
US prescribing information · 49606d5e-f45f-45eb-9ab8-15aa6a233875 · read 2026-08-30
On people with reduced kidney function, the label states: “Population pharmacokinetic analysis showed that the pharmacokinetics of darunavir were not significantly affected in HIV-infected subjects with moderate renal impairment (CrCL between 30 to 60 mL/min, n=20).”
US prescribing information · 49606d5e-f45f-45eb-9ab8-15aa6a233875 · read 2026-08-30
Where the result stopped carrying
Standard clinical resistance genotyping does not sequence Gag, so the escape route that eight of eight darunavir rebounders in one trial actually used is invisible to it
Maintenance monotherapy preserved future drug options over eight years but produced serious clinical events in 7.8% against 4.1%, p=0.08, and is not a recommended strategy
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 and oral suspension, always with a pharmacokinetic booster
✎ 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 with food, always with ritonavir or cobicistat. The booster requirement is not a convenience: unboosted exposure is too low to be therapeutic, and the label has no unboosted regimen. Absorption is substantially reduced 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 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 skin reactions including Stevens-Johnson syndrome, toxic epidermal necrolysis and drug reaction with eosinophilia and systemic symptoms are labelled; darunavir contains a sulfonamide moiety and rash is among the commonest adverse reactions. Hepatotoxicity including drug-induced hepatitis is labelled, with higher risk in hepatitis B or C co-infection. Gastrointestinal effects occurred at roughly half the rate of lopinavir-ritonavir in ARTEMIS. Hyperglycaemia, fat redistribution and immune reconstitution inflammatory syndrome are class effects. The cardiovascular association reported in the D:A:D cohort is described in the audits above and remains unexplained.
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 and oral suspension, always with a pharmacokinetic booster
✎ 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
The booster requirement is not a convenience: unboosted exposure is too low to be therapeutic, and the label has no unboosted regimen. Absorption is substantially reduced 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 which forms are sold and how they compare.
No source is stored against this line.
What is recorded as being sold
32 products list this as an active ingredient in the United States drug directory. 30 of them contain it and nothing else.
FDA National Drug Code directory · 72205-185 · read 2026-08-29
They are sold as powder, tablet and tablet, film coated, taken oral.
FDA National Drug Code directory · 72205-185 · read 2026-08-29
The regulator's established pharmacologic class for it is cytochrome p450 2d6 inhibitors [moa], cytochrome p450 3a inhibitors [moa] and hiv protease inhibitors [moa].
FDA National Drug Code directory · 72205-185 · read 2026-08-29
17 published labels name it as an active ingredient. 16 of them describe this substance alone, which is where its own label text on this page comes from.
US prescribing information · 88910ad0-6dc3-4a47-8a6b-5c6ee79f2a93 · read 2026-08-29
Those labels are classed as human prescription drug.
US prescribing information · 88910ad0-6dc3-4a47-8a6b-5c6ee79f2a93 · read 2026-08-29
Darunavir is oral at 3 DOSAGE FORMS AND STRENGTHS 600 mg: Yellow, oval shaped, biconvex, film-coated tablets debossed with 'V' on one side and '5' on the other side. 800 mg: Yellow, oval shaped, biconvex, film-coated tablets debossed with '…, recorded as fda label in effect 2025-03-19 in the United States.
US prescribing information · 49606d5e-f45f-45eb-9ab8-15aa6a233875 · read 2026-08-30
Recorded price in US: 1.21257–2.48844 USD per one unit as the pricing file counts it — a tablet, capsule, patch or single item, across 22 priced products whose strengths and pack forms differ, as of 2026-08-26, paid by retail pharmacies buying the product, as surveyed by the Centers for Medicare & Medicaid Services. It is not a list price, an insurance price, or what anyone pays at a counter..
Recorded source · 2026-08-26 · read 2026-08-28
Evidence carries across two names for one substance. It does not carry across a salt, a mirror form or a mixture.
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 Darunavir 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 cumulative darunavir exposure causes cardiovascular disease — a dose-dependent observational association with an internal null comparator, no mechanism and no randomised test
Why it sounds right. It follows from something real on this page: a body step, an animal result or a related finding.
The missing step. Nobody measured this in people for this use, or the study that did measure it did not show it.
What would change this
A study in people, for this exact use, measuring this exact thing, that a reviewer signs off.
RNAWiki has not yet published a reviewed conclusion for this use.
✗Goes past the evidence
That the tablet acquisition cost approximates the cost of treatment, when the mandatory booster is a separate product carrying its own price and interaction burden
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 an absent protease resistance mutation means an absent resistance mechanism, when Gag cleavage-site substitutions confer ten-fold resistance outside the region clinical genotyping reads
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 Darunavir 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
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POWER 1 and 2: 61% responded against 15% on comparator protease inhibitors
In plain words
In patients whose virus had already defeated multiple protease inhibitors, darunavir produced a meaningful viral load drop in 61% against 15% on whichever comparator the investigator chose. That is one of the largest treatment effects in the antiretroviral literature.
What was measured
Proportion with a viral load reduction of at least 1 log10 copies per millilitre at week 48, difference 46% (95% CI 35 to 57)
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
POWER 1 and POWER 2 (TMC114-C213 and TMC114-C202, NCT00071097) were phase IIB trials in treatment-experienced patients, pooled for a week 48 subgroup analysis restricted to those on the eventual recommended dose of darunavir-ritonavir 600/100 mg twice daily from baseline, each with an optimised background regimen. At week 48, 67 of 110 (61%) darunavir patients against 18 of 120 (15%) control protease inhibitor patients had a viral load reduction of at least 1 log10 copies per millilitre from baseline, difference in response rates 46% (95% CI 35 to 57, p<0.0001). A logistic regression adjusting for baseline primary protease mutation count, enfuvirtide use, baseline viral load and study gave a difference of 50% and an odds ratio of 11.72 (95% CI 5.75 to 23.89). Adverse event rates in the darunavir group were mostly lower than or similar to control when corrected for exposure.
Written into the record, not signed off as a reviewed claim
TITAN: better than lopinavir, and a third of the emergent protease resistance
In plain words
In 595 treatment-experienced patients, darunavir suppressed 77% against 68% for lopinavir. More importantly, when patients did fail, far fewer of the darunavir failures had developed new protease mutations, so fewer future options were lost.
What was measured
Proportion below 400 copies per millilitre at week 48, difference 9% (95% CI 2 to 16), and counts of emergent primary protease mutations
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
TITAN (TMC114-C214, NCT00110877) randomised 595 treatment-experienced, lopinavir-naive patients, open-label, to darunavir-ritonavir 600/100 mg twice daily or lopinavir-ritonavir 400/100 mg twice daily, each with an optimised background regimen. Of these, 187 (31%) were protease-inhibitor naive and 476 of 582 (82%) were susceptible to four or more protease inhibitors. At week 48, 220 of 286 (77%) against 199 of 293 (68%) had HIV RNA below 400 copies per millilitre, estimated difference 9% (95% CI 2 to 16), meeting the non-inferiority margin and favouring darunavir. Among virological failures, primary protease mutations developed in 6 (21%) darunavir patients against 20 (36%) lopinavir patients, and nucleoside analogue mutations in 4 (14%) against 15 (27%). Grade 3 or 4 adverse events occurred in 80 (27%) against 89 (30%).
Written into the record, not signed off as a reviewed claim
ARTEMIS: it also won where the virus had never seen a protease inhibitor
In plain words
In 689 people starting treatment for the first time, darunavir reached 84% suppressed against 78% for lopinavir, and the gap widened in people who started with a high viral load. Almost nobody who failed developed protease resistance.
What was measured
Proportion below 50 copies per millilitre at week 48, difference 5.6% (95% CI -0.1 to 11), with 79% against 67% above 100,000 copies per millilitre at baseline
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
ARTEMIS (TMC114-C211, NCT00258557) randomised 689 treatment-naive patients, open-label, to once-daily darunavir-ritonavir 800/100 mg or to lopinavir-ritonavir 800/200 mg total daily dose, each with fixed-dose tenofovir disoproxil and emtricitabine. Mean baseline HIV-1 RNA was 4.85 log10 copies per millilitre and median CD4 count 225 cells per microlitre. At week 48, 84% against 78% reached below 50 copies per millilitre, estimated difference 5.6% (95% CI -0.1 to 11), non-inferiority p<0.001. In the stratum starting at or above 100,000 copies per millilitre, response was 79% against 67% (p<0.05). Grade 2 to 4 gastrointestinal adverse events possibly related to treatment occurred in 7% against 14%, moderate-to-severe diarrhoea in 4% against 10%, and discontinuation for adverse events in 3% against 7%. By week 96 the virological failure rate was 12% against 17% (p=0.0437), and among failures with genotypes at both baseline and endpoint no major protease resistance mutations developed in either arm, with all failures remaining phenotypically susceptible to every protease inhibitor.
Written into the record, not signed off as a reviewed claim
Cohort data associate it with cardiovascular disease; the comparator in the same class shows nothing
In plain words
A 35,711-person cohort followed for seven years found the rate of heart attacks and strokes rising steadily with years of darunavir exposure, from about 5 events per 1,000 person-years in people never exposed to nearly 14 in those exposed for more than six years. Atazanavir, in the same class and the same analysis, showed almost nothing.
What was measured
That cumulative darunavir-ritonavir exposure causes cardiovascular disease — a dose-dependent observational association with an internal null comparator, no established mechanism, and no randomised test
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
The D:A:D study followed 35,711 people with HIV across 11 cohorts in Australia, Europe and the USA from 2009, for a median 6.96 years, with centrally validated myocardial infarction, stroke, sudden cardiac death and invasive cardiovascular procedures as the outcome. 1,157 cardiovascular events occurred, an incidence of 5.34 per 1,000 person-years (95% CI 5.03 to 5.65). Incidence rose from 4.91 per 1,000 person-years (4.59 to 5.23) in people never exposed to ritonavir-boosted darunavir to 13.67 (8.51 to 18.82) in those exposed for more than six years. After adjustment the incidence rate ratio was 1.59 (95% CI 1.33 to 1.91) per five additional years of darunavir-ritonavir use, and 1.03 (0.90 to 1.18) for atazanavir-ritonavir. The association survived adjustment for time-updated factors on the causal pathway, separate analysis of myocardial infarction and stroke, adjustment for bilirubin, and stratification by whether darunavir was the first protease inhibitor used. The authors state plainly that causal inference is limited by the observational design and call for investigation of a mechanism. No mechanism has been established, and no randomised trial has cardiovascular events as an endpoint. The dose-response relationship and the internal comparator make confounding by indication a harder explanation than usual, without ruling it out.
Written into the record, not signed off as a reviewed claim
Resistance testing reads the protease gene, and the resistance is not always there
In plain words
Clinical resistance tests sequence the protease gene. Patients failing darunavir often have a completely normal protease sequence, and the resistance has instead appeared in the protein the protease cuts. One such change confers ten-fold resistance and would be invisible to the test a clinician orders.
What was measured
Zero protease resistance mutations against eight of eight rebounders carrying Gag cleavage-site substitutions; T375A conferred ten-fold phenotypic resistance
Effect estimate
No reviewed effect estimate exists for this record.
Limits
This entry records a failure.
From the source
A resistance analysis of samples from a 48-week randomised trial in Cameroon, comparing ritonavir-boosted darunavir monotherapy (n=81) with tenofovir-lamivudine plus ritonavir-boosted lopinavir (n=39), sequenced protease and reverse transcriptase by ultradeep methods and Gag-protease by bulk sequencing at rebound. Among eight participants with virological rebound on darunavir, contributing twelve samples, no darunavir resistance-associated mutations were found in protease. All eight carried Gag mutations associated with protease inhibitor exposure, including T375N and T375A at the p2/p7 cleavage site, K436R at p7/p1, and substitutions in p17, p24, p2 and p6. Site-directed T375A conferred ten-fold darunavir resistance in a single-cycle phenotypic assay and increased replication capacity. Standard clinical genotyping does not sequence Gag. So the high genetic barrier is real, and part of what makes it look even higher than it is, is that one of the escape routes is outside the region the assay reads.
Written into the record, not signed off as a reviewed claim
PIVOT: eight years of protease inhibitor monotherapy, and future options preserved
In plain words
A pragmatic trial randomised 587 suppressed patients either to stay on three drugs or to drop to a single boosted protease inhibitor with prompt return to combination therapy if virus rebounded. After more than eight years, the proportion who had lost a future drug option was 2.1% against 2.7%. Only one patient in the monotherapy group developed resistance to the drug they were on.
What was measured
Cumulative eight-year risk of losing a future drug option: 2.1% against 2.7%, difference -0.6% (95% CI -3.2 to 2.0)
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
PIVOT (ISRCTN04857074) randomised 587 UK participants with viral load below 50 copies per millilitre for at least 24 weeks to maintain triple therapy (291) or switch to physician-selected protease inhibitor monotherapy with prompt reintroduction of combination therapy on rebound (296), between November 2008 and July 2010, and followed them in routine care for a median of more than 100 months. Loss of one or more future drug options had occurred in 7 triple-therapy and 6 monotherapy participants, cumulative risk at eight years 2.7% and 2.1%, difference -0.6% (95% CI -3.2% to 2.0%). Only one monotherapy participant developed resistance to the protease inhibitor they were taking, and that drug was atazanavir. Serious clinical events, comprising death, serious AIDS and serious non-AIDS events, occurred in 12 of 291 (4.1%) and 23 of 296 (7.8%), p=0.08, across the whole follow-up. The authors state that a small excess risk of serious clinical events with the monotherapy strategy cannot be excluded. Maintenance monotherapy is not a recommended strategy, and this result is worth reading as a measurement of the class resistance barrier rather than as an endorsement of it.
Written into the record, not signed off as a reviewed claim
The tablet is generic; the regimen is not, because it cannot be taken alone
In plain words
Darunavir costs US$2.49 a tablet. It cannot be used without a second drug whose only job is to slow its breakdown, and that booster brings an interaction list with it. Quoting the tablet price as the cost of the treatment is the most common way this drug is misdescribed.
What was measured
That the tablet acquisition cost shown on this page approximates the cost of treatment with this drug — it does not, because the mandatory booster is a separate product with its own price and its own interaction burden
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
Darunavir is cleared by CYP3A4 and requires co-administration with ritonavir or cobicistat to reach and hold therapeutic concentrations. Both boosters are potent CYP3A inhibitors, so the interaction profile of a darunavir regimen is the interaction profile of the booster, and it reaches statins, anticoagulants, inhaled and intranasal corticosteroids, several antiarrhythmics, some anticonvulsants and hormonal contraception. The CMS NADAC line quoted on this page is for the darunavir tablet alone. The economic and clinical unit is the boosted regimen, and no verified acquisition cost for a complete boosted regimen was assembled here. This is stated as an inference rather than a measurement because the direction is clear and the magnitude was not established from a source.
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What is not here
7 questions this page could not answer
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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 protease inhibitor that binds the backbone of the enzyme rather than its side chains, so mutations that reshape the active site do not shake it loose; it suppressed 61% of heavily treatment-experienced patients against 15% on comparator protease inhibitors, beat lopinavir in both treatment-naive and treatment-experienced trials, and produces virological failure that usually carries no protease resistance at all.
Recorded evidence blocks (10)
Q1
On the Darunavir label: indicated for what?
"Darunavir tablets, co-administered with ritonavir (darunavir/ritonavir), in combination with other antiretroviral agents, is indicated for the treatment of human immunodeficiency virus (HIV-1) infection in adult and pediatric patients 3 years of age and older [see Use in Specific Populations (8.4) and Clinical Studies…": indications and usage on Darunavir's label. DailyMed label · e80e44f8-1987-4b78-a63d-a4e4d5122ddb · 2026-03-11
Q2
109 registered trials of Darunavir — at which phases?
"Difficulties in recruitment due to a change in the nature of practice."; 9 of 109 registered studies
Show the evidence
Trial
NCT00765154
terminated; "Difficulties in recruitment due to a change in the nature of practice."
NCT00855413
terminated; "Study halted by sponsor due to slow enrollment."
NCT02116660
terminated; "This study was terminated early due to poor recruitment."
NCT02470650
withdrawn; "No participants enrolled"
NCT02503462
terminated; "No additional patients fulfilling the inclusion criteria"
NCT03472326
terminated; "GS-9131 did not meet the targeted antiviral response"
3 further recorded trials
NCT04183738
withdrawn; "In the context of COVID-19 pandemic."
NCT04236453
terminated; "COVID-19 pandemic impacted the BE assessment of the trial. The clinical team decided to terminate the trial in order to start a new pivotal BE trial"
NCT04240210
terminated; "Lack of eligible enrollees/ Halted by Primary Sponsor"
recorded 2026-09-01 · last checked 2026-09-04
Q4
Human studies of Darunavir used darunavir 800 mg — over how long?
Human studies of Darunavir used "darunavir 800 mg". ClinicalTrials.gov · 2026-09-01
Show the evidence
humanNCT00525733
darunavir 800 mg
recorded 2026-09-01 · last checked 2026-09-04
Q5
Darunavir's half-life is 15 hours — which schedules were studied?
15 hours; The terminal elimination half-life of darunavir was approximately 15 hours when co-administered with ritonavir.
tmaxpharmacokinetics
2.5-4 hours; Absorption and Bioavailability Darunavir, co-administered with 100 mg ritonavir twice daily, was absorbed following oral administration with a T max of approximately 2.5-4 hours.
bioavailabilitypharmacokinetics
37 %; The absolute oral bioavailability of a single 600 mg dose of darunavir alone and after co-administration with 100 mg ritonavir twice daily was 37% and 82%, respectively.
metabolismpharmacokinetics
Pharmacokinetics in Adults General Darunavir is primarily metabolized by CYP3A.
recorded 2026-03-11 · last checked 2026-09-04
Q6
Which 52 trials of Darunavir posted no result?
Posted no result
52 of 52 completed trials
Registrations
NCT00964327, NCT00115050, NCT01810887, NCT00752310, NCT00081588 and NCT00744887, and 46 more
Completion dates
oldest 2003-10; newest 2024-01-15
Show the evidence
Trial
NCT00964327
2003-10
NCT00115050
2007-06
NCT01810887
2008-07
NCT00752310
2008-08
NCT00081588
2008-12
NCT00744887
2008-12
14 further recorded trials
NCT02187107
2009-03
NCT00260078
2009-04
NCT00783484
2009-05
NCT00867152
2009-05
NCT00460382
2009-09
NCT00421551
2011-02
NCT00855088
2011-02
NCT00355524
2011-03
NCT01308658
2011-05
NCT00936793
2011-06-10
NCT01323257
2011-08
NCT00849160
2011-09
NCT01519336
2012-03
NCT01619527
2012-08
Q7
At the median, Darunavir's trials enrolled 52 people — anything larger?
Median enrolment
52
Largest enrolment
1814
Registered trials counted
108
Q8
What do 1924 spontaneous reports say about Darunavir — 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.
Darunavir appears in spontaneous reports to regulators. Across the 10 most-reported reaction terms, 1924 reaction mentions were counted: drug interaction 444; virologic failure 233; abortion spontaneous 226; drug resistance 204. FAERS via Open Targets · CHEMBL1201127 · 2026-06-24
Show the evidence
drug interaction
444
virologic failure
233
abortion spontaneous
226
drug resistance
204
premature baby
185
immune reconstitution inflammatory syndrome
162
4 more recorded rows
lipodystrophy acquired
143
viral load increased
135
cushing's syndrome
97
blood hiv rna increased
95
recorded 2026-06-24 · last checked 2026-09-04
Q9
Which 10 reactions does Darunavir's label not list?
( 4 , 5.5 , 7 , 12.3 ) 7.1 Potential for darunavir/ritonavir to Affect Other Drugs Darunavir co-administered with ritonavir is an inhibitor of CYP3A, CYP2D6, and P-gp.
drug_interactions
Co-administration of darunavir and ritonavir with drugs that are primarily metabolized by CYP3A and CYP2D6 or are transported by P-gp may result in increased plasma concentrations of such drugs, which could increase or prolong their therapeutic effect and adverse events.
drug_interactions
Darunavir co-administered with ritonavir with drugs that have active metabolite(s) formed by CYP3A may result in reduced plasma concentrations of these active metabolite(s), potentially leading to loss of their therapeutic effect (see Table 10).
drug_interactions
7.2 Potential for Other Drugs to Affect Darunavir Darunavir and ritonavir are metabolized by CYP3A.
drug_interactions
In vitro data indicate that darunavir may be a P-gp substrate.
drug_interactions
Drugs that induce CYP3A activity would be expected to increase the clearance of darunavir and ritonavir, resulting in lowered plasma concentrations of darunavir and ritonavir.
2 more recorded rows
Interaction statementdrug_interactions
Co-administration of darunavir and ritonavir and other drugs that inhibit CYP3A, or P-gp may decrease the clearance of darunavir and ritonavir and may result in increased plasma concentrations of darunavir and ritonavir (see Table 10).
Interaction statementdrug_interactions
Refer to apixaban dosing instructions for co-administration with P-gp and strong CYP3A inhibitors in apixaban prescribing information.
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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