This page shows what was measured, who it was measured in, and what that does not settle.
What Doravirine does in the body
HIV-1 infection, as part of a combination regimen
Reverse transcriptase has to flex through a cycle of shapes to copy genetic material. Doravirine wedges into a greasy pocket just beside the working part of the enzyme and holds the whole structure rigid, so the cycle cannot complete. The first drug that did this, efavirenz, was thrown out by a single change to that pocket. Doravirine was designed after the shape of that changed pocket was known, so it still fits.
What happened in people
Dizziness in 8.8% against 37.1% and sleep disturbance in 12.1% against 25.2% against efavirenz; neuropsychiatric events 25.0% against 55.9% in the integrated analysis
✎ 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.
Positioned in guidelines as an alternative rather than a preferred first-line agent, used where an integrase inhibitor is not appropriate
Where it acts
HIV-1 reverse transcriptase in the cytoplasm of infected CD4-positive T cells
Kind of result
Symptoms and quality of life
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 · 913P6LK81M · read 2026-08-29
Its recorded molecular formula is C17H11ClF3N5O3, weighing 425.75.
US prescribing information · 76ce1f00-28c0-4314-bd2c-d473fe3d0970 · 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 111 words.
Words this page uses
Four words worth knowing first
Chosen from what this page shows, with each one explained before the word it depends on.
Comparator
A comparator is whatever the treatment was measured against.
A picture of it, and where the picture fails
It is like the other runner in a race.
Where that stops being true. A race has one winner. A study can show both arms improved.
What people get wrong. Results are read without asking what the other group got. Beating nothing is not beating a treatment.
The control condition against which the experimental intervention is assessed.
Randomisation
Randomisation means chance decides who gets which treatment.
A picture of it, and where the picture fails
It is like a coin toss deciding the groups.
Where that stops being true. A coin toss is fair once. Fairness here comes from doing it for everyone.
What people get wrong. It is thought to make groups identical. It makes them similar on average, including on things nobody measured.
Allocation of participants to arms by a chance process, so that unmeasured factors are balanced in expectation.
Absolute difference
An absolute difference is how many more people in a hundred were affected.
A picture of it, and where the picture fails
It is like counting heads in two rooms of a hundred.
Where that stops being true. Heads are easy to count. Study results carry a margin of error too.
What people get wrong. It is confused with a percentage change, which can look far larger.
The arithmetic difference in event rates between arms.
Confidence interval
A confidence interval is the range the true answer is likely to sit in.
A picture of it, and where the picture fails
It is like a weather forecast giving a range rather than one number.
Where that stops being true. A forecast range covers tomorrow. This one covers what the study could resolve.
What people get wrong. The middle number is read as the answer. A range crossing zero means no change is still possible.
An interval estimate that would contain the true parameter in a stated proportion of repeated studies.
What happened in people◇Read from sources, not yet reviewed
What happened in people
Each card is one study: the exact question it asked, who was in it, and whether it showed what it set out to show.
Proportion with HIV-1 RNA below 50 copies per millilitre at week 48 by FDA snapshot, against efavirenz-emtricitabine-tenofovir disoproxil
✓ The study showed what it set out to show
Who was studied
DRIVE-AHEAD (NCT02403674)
How many people
728
Study design
Phase 3, randomised, double-blind, non-inferiority, 48-week primary with 96-week follow-up
Compared against
Not recorded for this study
Kind of result
A number that stands in for health
What was found
84.3% versus 80.8%, difference 3.5% (95% CI -2.0 to 9.0) against a 10% margin; at week 96, 77.5% versus 73.6%, difference 3.8% (95% CI -2.4 to 10.0)
Repeated elsewhere
Replicated
What this does not prove. Meeting one endpoint in one population does not carry to other goals or other people.
The limits of this study, and where it came from
Main limit. Prespecified neuropsychiatric events were the differentiating result and were secondary endpoints: dizziness 8.8% against 37.1%, sleep disturbance 12.1% against 25.2%.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Oral film-coated tablet, as a single agent and as a fixed-dose combination with lamivudine and tenofovir disoproxil
Interval reported. 95% CI -2
Written into the record, not signed off as a reviewed claim.
84% versus 80%, difference 3.9% (95% CI -1.6 to 9.4); at week 96, 73% versus 66%, difference 7.1% (95% CI 0.5 to 13.7)
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 comparator was a boosted protease inhibitor that guidelines had already moved away from by the time the drug was approved. No randomised comparison against an integrase inhibitor in treatment-naive adults exists.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Oral film-coated tablet, as a single agent and as a fixed-dose combination with lamivudine and tenofovir disoproxil
Interval reported. 95% CI -1
Written into the record, not signed off as a reviewed claim.
Maintenance of HIV-1 RNA below 50 copies per millilitre after switching from a stable suppressive regimen to fixed-dose doravirine-lamivudine-tenofovir disoproxil
✓ The study showed what it set out to show
Who was studied
DRIVE-SHIFT (NCT02397096)
How many people
647
Study design
Phase 3, randomised, open-label, immediate against delayed switch, 48-week primary with 144-week follow-up
Compared against
Not recorded for this study
Kind of result
A number that stands in for health
What was found
At week 144, 80.1% (351/438) of the immediate-switch group and 83.7% (175/209) of the delayed-switch group maintained below 50 copies per millilitre
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. Non-treatment-related discontinuations were higher in Black than in non-Black participants in this trial, in a study population where Black participants were under 20% of the total.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Oral film-coated tablet, as a single agent and as a fixed-dose combination with lamivudine and tenofovir disoproxil
Interval reported. Not recorded in this summary
Written into the record, not signed off as a reviewed claim.
Proportion of participants discontinuing because of adverse events through week 48, doravirine against efavirenz and against ritonavir-boosted darunavir
✓ The study showed what it set out to show
Who was studied
Integrated safety analysis of P007, DRIVE-FORWARD and DRIVE-AHEAD
How many people
1500
Study design
Prespecified integrated safety analysis of three double-blind trials at week 48
Compared against
Not recorded for this study
Kind of result
A number that stands in for health
What was found
Discontinuation for adverse events 2.5% on doravirine against 6.6% on efavirenz, treatment difference -3.4% (95% CI -6.2 to -0.8, p=0.012), and 3.1% on boosted darunavir
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. Neuropsychiatric adverse events occurred in 25.0% on doravirine against 55.9% on efavirenz, and drug-related adverse events in 30.9% against 61.4%.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Oral film-coated tablet, as a single agent and as a fixed-dose combination with lamivudine and tenofovir disoproxil
Interval reported. 95% CI -6
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
Doravirine
What a person takes: Oral film-coated tablet, as a single agent and as a fixed-dose combination with lamivudine and tenofovir disoproxil.
The measurement behind this step
Taken once daily with or without food. No pharmacokinetic booster is required and there is no gastric pH dependence. Strong CYP3A inducers, principally rifampicin and rifapentine, are contraindicated because exposure falls far enough to risk loss of virological response and class resistance.
Getting in
Swallowed once a day, with or without food, and without a booster
One tablet daily, alone or in a three-drug combination tablet. No food requirement, no second drug needed to keep it in the body, and a short interaction list.
╌╌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
Doravirine is cleared principally by CYP3A4 oxidation and requires no pharmacokinetic booster. It is not a clinically significant inhibitor or inducer itself, so the interaction profile is dominated by strong CYP3A inducers such as rifampicin and rifapentine, which are contraindicated. Unlike rilpivirine it has no gastric pH dependence and no meal requirement, and unlike efavirenz it does not induce its own metabolism.
The molecule diffuses into cells as it is. It does not have to be converted into anything else first, unlike the nucleoside drugs it is combined with.
╌╌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
Doravirine is passively permeable and is not a prodrug, in contrast to the nucleoside and nucleotide analogues in its fixed-dose partner tablet, all of which must be phosphorylated before they act. Its central nervous system penetration is lower than efavirenz, which is the pharmacological account of the neuropsychiatric difference measured in DRIVE-AHEAD.
It wedges into the pocket beside the copying machinery
Beside the working part of reverse transcriptase is a greasy gap. Doravirine forces its way in and stays, holding the enzyme in a shape it cannot work from.
╌╌Described, with no measurement named. No measurement is named for this step, so it is drawn as an unconfirmed link.
The measurement behind this step
Binding is to the non-nucleoside pocket in the p66 subunit, roughly 10 angstroms from the polymerase catalytic triad, and inhibition is allosteric and non-competitive with respect to the nucleotide substrate. The 3-chloro-5-cyanophenoxy group and the trifluoromethyl pyridinone core were selected so that the contacts do not depend on residues 103 and 181, which are the positions the first-generation drugs relied on and the virus most readily changes.
The enzyme cannot flex, so copying stops, and the usual escape routes are closed
With the drug wedged in place the enzyme is rigid and cannot complete its cycle. The two changes that would normally throw a drug like this out of the pocket do not throw this one out.
╌╌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
Binding restricts mobility of the thumb subdomain and the primer grip so the enzyme cannot execute the conformational change that follows nucleotide binding. Activity is retained against K103N, Y181C, G190A and the K103N/Y181C double mutant. Escape instead requires V106A or V106I, F227C or Y318F, substitutions that carry replicative fitness costs, which is why treatment-emergent resistance was rare across the registration programme and why no additional doravirine resistance emerged between weeks 48 and 96 in DRIVE-AHEAD.
Virus falls, with less dizziness and lower cholesterol than the drug it replaced
Suppression rates match the comparators. The measurable differences are elsewhere: far less dizziness and sleep disturbance than efavirenz, and cholesterol that goes down rather than up.
╌╌Described, with no measurement named. No measurement is named for this step, so it is drawn as an unconfirmed link.
The measurement behind this step
Suppression below 50 copies per millilitre was 84.3% against 80.8% at week 48 against efavirenz and 84% against 80% against boosted darunavir, rising to a 7.1 percentage-point advantage over darunavir by week 96. Dizziness occurred in 8.8% against 37.1% and sleep disturbance in 12.1% against 25.2%. Fasting LDL cholesterol changed by -1.6 against +8.7 mg/dL against efavirenz and by a between-group difference of -14.6 mg/dL against darunavir. The total cholesterol to HDL ratio, which is the measure most tied to cardiovascular risk, did not differ at week 96.
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 who need an alternative to an integrase inhibitor, commonly because of a drug interaction or because of weight gain, and people switching from an older non-nucleoside or from a boosted protease inhibitor.
Who is missing from the studies
Which groups were under-represented in the studies has not been recorded for this substance. Pregnancy, breastfeeding, children, older adults, and people with liver or kidney conditions are commonly excluded from trials; nothing here says whether they were.
What the label states about particular groups
On pediatric, the label states: “Safety and efficacy of PIFELTRO in pediatric patients weighing less than 35 kg have not been established.”
US prescribing information · 76ce1f00-28c0-4314-bd2c-d473fe3d0970 · read 2026-08-30
On older people, the label states: “Clinical trials of PIFELTRO did not include sufficient numbers of participants aged 65 years and over to determine whether they respond differently from younger participants.”
US prescribing information · 76ce1f00-28c0-4314-bd2c-d473fe3d0970 · read 2026-08-30
On people who are pregnant, the label states: “Exposure Registry There is a pregnancy exposure registry that monitors pregnancy outcomes in individuals exposed to PIFELTRO during pregnancy.”
US prescribing information · 76ce1f00-28c0-4314-bd2c-d473fe3d0970 · read 2026-08-30
On people who are breastfeeding, the label states: “Risk Summary It is unknown whether doravirine is present in human milk, affects human milk production, or has effects on the breastfed infant.”
US prescribing information · 76ce1f00-28c0-4314-bd2c-d473fe3d0970 · read 2026-08-30
On people with reduced liver function, the label states: “No dosage adjustment of PIFELTRO is required in patients with mild (Child-Pugh Class A) or moderate (Child-Pugh Class B) hepatic impairment.”
US prescribing information · 76ce1f00-28c0-4314-bd2c-d473fe3d0970 · read 2026-08-30
On people with reduced kidney function, the label states: “No dosage adjustment of PIFELTRO is required in patients with mild, moderate, or severe renal impairment.”
US prescribing information · 76ce1f00-28c0-4314-bd2c-d473fe3d0970 · read 2026-08-30
Where the result stopped carrying
The registration programme enrolled women and Black participants at under 20% each, and its own subgroup analysis states that sample size was limited and calls for greater diversity in future studies
All three comparators were drugs that major guidelines had already moved away from by the time the drug reached the market in 2018
This is a scope explorer, not a diagnosis engine.
It shows who was studied so you can see whether people similar to you were included.
RNAWiki cannot tell whether a study fits you. It can show who was in it.
What it would be like to take◇Read from sources, not yet reviewed
Why it might seem to do nothing
A real effect and a noticed effect are different things. These are the recorded reasons the two come apart.
It was studied in different people
The people in the studies were not much like the reader.
On this record: Which groups were under-represented in the studies has not been recorded for this substance. Pregnancy, breastfeeding, children, older adults, and people with liver or kidney conditions are commonly excluded from trials; nothing here says whether they were.
The evidence may simply be wrong
Small early studies often do not hold up.
On this record: RNAWiki has not yet published a reviewed conclusion for this use.
Other reasons RNAWiki checked and found nothing for (11)
It was studied for a different goal
The studies measured something else entirely. Nothing in this record points to this reason.
A different form was studied
The studied form is not the form on the shelf. Nothing in this record points to this reason.
There was nothing to correct
Where a level is already normal, topping it up may change nothing. Nothing in this record points to this reason.
Something else had to happen too
In the studies it was paired with training, a diet or another treatment. Nothing in this record points to this reason.
The change is too small to feel
A real change can still sit below what a person notices. Nothing in this record points to this reason.
Day-to-day swing hides it
Sleep, food, stress and time of day move most numbers more than this would. Nothing in this record points to this reason.
Not enough time yet
The studies ran longer than the person has waited. Nothing in this record points to this reason.
It was not taken as studied
Missed days change the result, and studies count them. Nothing in this record points to this reason.
Something else changed at the same time
Two changes at once cannot be told apart afterwards. Nothing in this record points to this reason.
The product may not be what it says
Contents of a sold product are not always what the label states. Nothing in this record points to this reason.
No recorded reason
RNAWiki has nothing stored that would explain it. Nothing in this record points to this reason.
None of these is a reason to take more. Taking more is not a step this page ever suggests.
What it would be like to take◇Read from sources, not yet reviewed
What taking it involves
The recorded facts about getting hold of it and using it. Nothing here is a suggestion about what you should do.
How it is supplied
Prescription only
❝ Quoted from a source
Where this came from
Copied from a source RNAWiki stored, with the source named.
Read from the recorded approval status.
No source is stored against this line.
Form and route
Oral film-coated tablet, as a single agent and as a fixed-dose combination with lamivudine and tenofovir disoproxil
✎ Source-linked record
Where this came from
A person wrote this into the record with the study named beside it. No reviewer has signed it off.
The form and route recorded on this substance.
No source is stored against this line.
Who oversees it
RNAWiki has not recorded a supervision or regulatory status for this substance.
❝ Quoted from a source
Where this came from
Copied from a source RNAWiki stored, with the source named.
No register row and no identity class settled the question.
No source is stored against this line.
What is in the pack
Taken once daily with or without food. No pharmacokinetic booster is required and there is no gastric pH dependence. Strong CYP3A inducers, principally rifampicin and rifapentine, are contraindicated because exposure falls far enough to risk loss of virological response and class resistance.
✎ 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
The fixed-dose combination carries a boxed warning for severe acute exacerbation of hepatitis B on discontinuation, contributed by its lamivudine and tenofovir components rather than by doravirine. Immune reconstitution inflammatory syndrome can follow suppression. Neuropsychiatric adverse events occur but at roughly half the efavirenz rate in the integrated analysis, 25.0% against 55.9%, and prespecified dizziness at 8.8% against 37.1%. Nausea, headache and diarrhoea are the commonest complaints. Discontinuation for adverse events was 2.5% at week 48 across the programme.
Nobody counted how many people took this and were fine, so this cannot be turned into a rate.
Over a long time. No completed tested study window is recorded, so long-term effects are not established by the registry record.
Groups the studies covered thinly. Which groups were under-represented in the studies has not been recorded for this substance. Pregnancy, breastfeeding, children, older adults, and people with liver or kidney conditions are commonly excluded from trials; nothing here says whether they were.
What is missing or unclear◇Read from sources, not yet reviewed
Does the exact form matter?
Evidence belongs to the exact thing that was tested. A different salt, a different mixture or a different preparation is a different question.
The form that was studied
Oral film-coated tablet, as a single agent and as a fixed-dose combination with lamivudine and tenofovir disoproxil
✎ 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
No pharmacokinetic booster is required and there is no gastric pH dependence. Strong CYP3A inducers, principally rifampicin and rifapentine, are contraindicated because exposure falls far enough to risk loss of virological response and class resistance.
✎ 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
13 products list this as an active ingredient in the United States drug directory. 9 of them contain it and nothing else.
FDA National Drug Code directory · 0006-5092 · read 2026-08-29
They are sold as powder and tablet, film coated, taken oral.
FDA National Drug Code directory · 0006-5092 · 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 · 0006-5092 · read 2026-08-29
4 published labels name it as an active ingredient. 2 of them describe this substance alone, which is where its own label text on this page comes from.
US prescribing information · 76ce1f00-28c0-4314-bd2c-d473fe3d0970 · read 2026-08-29
Those labels are classed as human prescription drug.
US prescribing information · 76ce1f00-28c0-4314-bd2c-d473fe3d0970 · read 2026-08-29
PIFELTRO is oral at 3 DOSAGE FORMS AND STRENGTHS PIFELTRO film-coated tablets are white, oval-shaped tablets, debossed with the corporate logo and 700 on one side and plain on the other side., recorded as fda label in effect 2026-07-08 in the United States.
US prescribing information · 76ce1f00-28c0-4314-bd2c-d473fe3d0970 · 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 Doravirine 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 efficacy against efavirenz and boosted darunavir establishes comparability with the integrase inhibitors that are the actual alternative, which has never been randomised in treatment-naive adults
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 LDL and non-HDL advantage produces fewer cardiovascular events, when the total cholesterol to HDL ratio did not differ at 96 weeks and no trial measured 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 weight neutrality on switching is a property of doravirine, when most participants were also taking tenofovir disoproxil, which independently suppresses weight
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 Doravirine 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.
DRIVE-AHEAD: non-inferior to efavirenz with a third of the dizziness
In plain words
In 728 people starting treatment, the doravirine tablet matched the efavirenz tablet on viral suppression, 84.3% against 80.8%. What separated them was tolerability: dizziness in 8.8% against 37.1%, and sleep disturbance in 12.1% against 25.2%.
What was measured
Proportion below 50 copies per millilitre at week 48, difference 3.5% (95% CI -2.0 to 9.0), with prespecified neuropsychiatric event rates and fasting lipid change
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
DRIVE-AHEAD (NCT02403674) was a phase 3, multicentre, double-blind non-inferiority trial randomising 734 treatment-naive adults with at least 1,000 HIV-1 RNA copies per millilitre to fixed-dose doravirine 100 mg with lamivudine and tenofovir disoproxil, or to efavirenz 600 mg with emtricitabine and tenofovir disoproxil; 728 were treated. At week 48, 307 of 364 (84.3%) against 294 of 364 (80.8%) had HIV-1 RNA below 50 copies per millilitre by FDA snapshot, difference 3.5% (95% CI -2.0 to 9.0) against a 10% margin. Prespecified neuropsychiatric events were significantly less frequent on doravirine: dizziness 8.8% against 37.1%, sleep disorders or disturbances 12.1% against 25.2%, altered sensorium 4.4% against 8.2%. Mean change in fasting LDL cholesterol was -1.6 against +8.7 mg/dL and non-HDL cholesterol -3.8 against +13.3 mg/dL, both significantly different. At week 96 suppression was 77.5% against 73.6%, difference 3.8% (95% CI -2.4 to 10.0), with no additional doravirine resistance emerging between weeks 48 and 96.
Written into the record, not signed off as a reviewed claim
DRIVE-FORWARD: ahead of boosted darunavir by 96 weeks, and 14.6 mg/dL lower on LDL
In plain words
Against a boosted protease inhibitor in 766 treated patients, doravirine matched it at 48 weeks and was ahead by 96, 73% against 66%. Cholesterol went down on doravirine and up on darunavir, and there was a third less diarrhoea.
What was measured
Proportion below 50 copies per millilitre at weeks 48 and 96, difference 3.9% (95% CI -1.6 to 9.4) and 7.1% (0.5 to 13.7)
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
DRIVE-FORWARD (NCT02275780) randomised 769 treatment-naive adults at 125 centres in 15 countries, double-blind, to doravirine 100 mg daily or ritonavir-boosted darunavir 800/100 mg daily, each with investigator-selected nucleosides; 383 in each group received at least one dose. At week 48, 321 of 383 (84%) against 306 of 383 (80%) were below 50 copies per millilitre, difference 3.9% (95% CI -1.6 to 9.4), meeting non-inferiority at a 10-percentage-point margin. At week 96, 277 of 383 (73%) against 248 of 383 (66%), difference 7.1% (95% CI 0.5 to 13.7). Treatment-emergent resistance to any study drug occurred in 2 of 383 (1%) on doravirine and 1 of 383 on darunavir. Mean changes from baseline differed significantly for LDL cholesterol, -14.6 mg/dL (95% CI -18.2 to -11.0), and non-HDL cholesterol, -18.4 mg/dL (-22.5 to -14.3). Diarrhoea occurred in 65 (17%) against 91 (24%) through week 96.
Written into the record, not signed off as a reviewed claim
It has never been randomised against the drug it actually competes with
In plain words
Doravirine was registered against efavirenz and against a boosted protease inhibitor. Neither is what a clinician is choosing between today. The real alternative is an integrase inhibitor, and that trial has not been run in people starting treatment.
What was measured
That efficacy demonstrated against efavirenz and against boosted darunavir establishes comparability with the second-generation integrase inhibitors that are the actual alternative
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
The registration programme comprised DRIVE-FORWARD against ritonavir-boosted darunavir, DRIVE-AHEAD against efavirenz, and DRIVE-SHIFT, a switch trial from a boosted regimen. By the time doravirine was approved in 2018, both the WHO and the United States guidelines had already moved first-line therapy to integrase inhibitors, so all three comparators were drugs the guidelines had moved away from. The one randomised comparison that does exist against an integrase inhibitor is ACTG A5391, and it enrolled 145 people with obesity who were already suppressed, switching them off an integrase inhibitor with tenofovir alafenamide; it was a weight trial, not an efficacy trial, and it found no clinically meaningful weight difference at 48 weeks. Claims that doravirine is comparable to dolutegravir or bictegravir in treatment-naive patients therefore rest on cross-trial comparison, which is exactly the kind of comparison the non-inferiority margins in these trials are wide enough to hide a real difference inside.
Written into the record, not signed off as a reviewed claim
The lipid advantage is measured on cholesterol, not on cardiovascular events
In plain words
LDL cholesterol falls on doravirine and rises on the drugs it was compared with, consistently and significantly. Whether that difference produces fewer heart attacks has not been tested, because no antiretroviral trial has ever been powered for cardiovascular endpoints.
What was measured
That the LDL and non-HDL cholesterol advantage translates into fewer cardiovascular events, when the total cholesterol to HDL ratio did not differ at 96 weeks and no trial has measured the events
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
Against efavirenz, mean fasting LDL cholesterol changed by -1.6 against +8.7 mg/dL and non-HDL cholesterol by -3.8 against +13.3 mg/dL at week 48, both significant. Against boosted darunavir, the between-group differences at week 96 were -14.6 mg/dL for LDL (95% CI -18.2 to -11.0) and -18.4 mg/dL for non-HDL (-22.5 to -14.3). In DRIVE-AHEAD at week 96 the mean change in the total cholesterol to HDL ratio, which is the lipid measure most directly tied to cardiovascular risk in the general population, was similar between groups. That last detail is the audit: the ratio is what the epidemiology of cardiovascular risk is built on, and on that measure the difference disappeared. A 14.6 mg/dL LDL difference is a real and consistent measurement, and the step from it to a difference in myocardial infarction is an extrapolation nobody has tested in this population.
Written into the record, not signed off as a reviewed claim
It survives K103N and Y181C, which is the whole reason it exists
In plain words
The substitutions that ended the first generation of this drug class are now common in people who have been treated before, and in some regions in people who have not. Doravirine keeps working against them, which is a narrow but genuinely useful property.
What was measured
Retained in-vitro activity against K103N, Y181C, G190A and K103N/Y181C, with an escape pathway through V106A/I, F227C and Y318F
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
Doravirine was selected for in-vitro activity against the most common non-nucleoside-resistant HIV-1 variants, including K103N, Y181C and G190A and the K103N/Y181C double mutant, and the label carries the resulting indication distinction. The reason this matters is regional and quantitative: a meta-regression of 358 datasets covering 56,044 adults estimated pretreatment non-nucleoside resistance in 2016 at 11.0% (95% CI 7.5 to 15.9) in southern Africa and 10.1% (5.1 to 19.4) in eastern Africa, against a WHO threshold of 10% for changing national first-line therapy. Its own escape pathway runs through V106A or V106I, F227C and Y318F. In DRIVE-AHEAD no additional doravirine resistance emerged between weeks 48 and 96, and in DRIVE-FORWARD treatment-emergent resistance to any study drug occurred in 2 of 383. It is a second-generation drug in a one-mutation class, not a drug with an integrase-inhibitor resistance barrier, and those are different claims.
Written into the record, not signed off as a reviewed claim
Weight-neutral on switching, in a field where that has become the question
In plain words
Weight gain on integrase inhibitors is the main reason people look for an alternative. Across three trials, switching to or continuing doravirine was weight-neutral overall, with more than half of participants holding stable weight.
What was measured
Mean weight change of +1.4 kg and +1.2 kg from switch through week 144 in DRIVE-SHIFT, with stable weight in more than 57% of pooled participants
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
A pooled analysis of DRIVE-FORWARD, DRIVE-AHEAD and DRIVE-SHIFT reported that switching to doravirine was weight-neutral overall, with more than 57% of participants having stable weight and more than 74% also receiving tenofovir disoproxil. In DRIVE-SHIFT through week 144, mean weight change from switch was +1.4 kg in the immediate-switch group and +1.2 kg in the delayed-switch group. Two confounders belong with these numbers and the authors identify them. First, most participants were also on tenofovir disoproxil, which independently suppresses weight, so part of what looks like doravirine neutrality is the backbone. Second, participants switching away from a weight-suppressive non-nucleoside were more likely to gain than those switching from a protease inhibitor, meaning the direction of measured change depends on what was stopped as much as on what was started. The randomised test of whether removing an integrase inhibitor in favour of doravirine reverses established weight gain is ACTG A5391, and it found no clinically meaningful difference at 48 weeks.
Written into the record, not signed off as a reviewed claim
The trials that established it enrolled almost no women and almost no Black participants
In plain words
Across all three registration trials, women and Black participants each made up under a fifth of the study populations. The analyses that looked for differences by sex and race found broadly similar results, and said in their own conclusion that the sample size was too small to be sure.
What was measured
Female and Black participants each under 20% of the population across three registration trials, with the subgroup analysis stating its own sample size was limited
Effect estimate
No reviewed effect estimate exists for this record.
Limits
This entry records a failure.
From the source
A long-term subgroup analysis across DRIVE-FORWARD, DRIVE-AHEAD and DRIVE-SHIFT reports that female and Black participants each represented under 20% of the study populations. Within that limit, proportions below 50 copies per millilitre were comparable between sex and race subgroups, CD4 changes and drug-related adverse event rates were generally similar, and the authors conclude that sample size was limited and that future studies should ensure greater diversity. Two signals within that analysis were not similar: in DRIVE-SHIFT, non-treatment-related discontinuations were higher in Black than in non-Black participants, and differences in median weight change were generally larger between race subgroups than between sex subgroups, with wide interquartile ranges throughout. A separate weight analysis found weight loss or stable weight more common in non-Black than in Black participants after switching to doravirine. None of these are efficacy failures. What failed is the enrolment: a drug positioned for regions where non-nucleoside resistance is highest was registered on a population that barely included the people who live there.
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The older medicine-wide conclusion held in this record
Written for a clinical reader, and about the medicine as a whole rather than about one indication, population and set of trials. RNAWiki does not treat it as a programme conclusion and no reviewer has signed it off in that form. It is here word for word because it is what the record holds.
A second-generation non-nucleoside inhibitor engineered to keep binding reverse transcriptase through the mutations that end efavirenz; it reached 84.3% suppressed at 48 weeks against 80.8% on efavirenz with a third of the dizziness (8.8% against 37.1%), and 84% against 80% on boosted darunavir with LDL cholesterol 14.6 mg/dL lower at 96 weeks — but it has never been randomised against the integrase inhibitors it actually competes with, and it remains a class defeated by single substitutions.
Recorded evidence blocks (9)
Q1
On the Doravirine label: indicated for what?
"PIFELTRO ® is indicated in combination with other antiretroviral agents for the treatment of HIV-1 infection in adults and pediatric patients weighing at least 35 kg: with no prior antiretroviral treatment history; OR to replace the current antiretroviral regimen in those who are virologically-suppressed (HIV-1 RNA…": indications and usage on Doravirine's label. DailyMed label · ff06e5cc-f47a-4779-816b-0e5b13e88a25 · 2026-07-09
Q2
44 registered trials of Doravirine — at which phases?
Registered studies posting no result
19 of 44
44 registered studies of Doravirine: 11 phase1, 11 phase4, 10 phase3, 7 phase2, 5 na or unstated, 1 early phase1. CLINICALTRIALS_SNAPSHOT · 2026-09-01
57 with a PubMed record
Show the evidence
phase1
11
phase4
11
phase3
10
phase2
7
na or unstated
5
early phase1
1
7 more recorded rows
completed
27
recruiting
5
unknown
5
terminated
3
not yet recruiting
2
active not recruiting
1
withdrawn
1
recorded 2026-09-01 · last checked 2026-09-04
Q3
4 of Doravirine's trials stopped: futility/efficacy, accrual/recruitment?
"The study was closed to accrual early based on Study Monitoring Committee review indicating that the study objectives had either been achieved or could not be met within a reasonable timeframe for the then-open arms."; 4 of 44 registered studies
Show the evidence
Trial
NCT04518228
terminated; "The study was closed to accrual early based on Study Monitoring Committee review indicating that the study objectives had either been achieved or could not be met within a reasonable timeframe for the then-open arms."
NCT04665375
terminated; "enrollment futility"
NCT05289986
terminated; "The CI, sponsor and funder jointly made the decision to end the trial due to lack of recruitment, as well as due to delays it was felt value of the primary endpoint had lessened to a point where its scientific value was questioned."
NCT05457530
withdrawn; "Due to No/Low enrollment"
recorded 2026-09-01 · last checked 2026-09-04
Q4
Human studies of Doravirine used Treatment A: Doravirine 100 mg film coated tablet — over how long?
Human studies of Doravirine used "Treatment A: Doravirine 100 mg film coated tablet". ClinicalTrials.gov · 2026-09-01
10 recorded entries; human; tablet; also "Treatment B: Doravirine 150 mg tablet (40% drug loaded granule)", "Treatment C: Doravirine 150 mg tablet (30% drug loaded granule)", "Treatment D: Doravirine 150 mg tablet (50% drug loaded granule)"
Show the evidence
human
NCT02549040
tablet; Treatment A: Doravirine 100 mg film coated tablet
NCT04433780, NCT04495348, NCT06719570 and NCT05761509
Completion dates
oldest 2023-03-31; newest 2024-06-30
Show the evidence
Trial
NCT04433780
2023-03-31
NCT04495348
2023-06-05
NCT06719570
2024-03-15
NCT05761509
2024-06-30
Q6
At the median, Doravirine's trials enrolled 33.5 people — anything larger?
Median enrolment
33.5
Largest enrolment
769
Registered trials counted
44
Q7
What do 20 spontaneous reports say about Doravirine — 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.
Doravirine appears in spontaneous reports to regulators. Across the 7 most-reported reaction terms, 20 reaction mentions were counted: drug reaction with eosinophilia and systemic symptoms 5; blood hiv rna increased 4; virologic failure 4; family stress 2. FAERS via Open Targets · CHEMBL2364608 · 2026-06-24
Show the evidence
drug reaction with eosinophilia and systemic symptoms
5
blood hiv rna increased
4
virologic failure
4
family stress
2
genotype drug resistance test positive
2
stress at work
2
1 more recorded row
adrenal androgen excess
1
recorded 2026-06-24 · last checked 2026-09-04
Q8
Which 7 reactions does Doravirine's label not list?
adrenal androgen excess, blood hiv rna increased and drug reaction with eosinophilia and systemic symptoms and 4 more reported for Doravirine, absent from its label. FAERS via Open Targets · CHEMBL2364608 · 2026-06-24
2 label terms; 7 reported and unlisted; ff06e5cc-f47a-4779-816b-0e5b13e88a25
Show the evidence
adrenal androgen excess
count not stated
blood hiv rna increased
count not stated
drug reaction with eosinophilia and systemic symptoms
count not stated
family stress
count not stated
genotype drug resistance test positive
count not stated
stress at work
count not stated
1 more recorded row
virologic failure
count not stated
recorded 2026-06-24 · last checked 2026-09-04
Q9
Doravirine and CYP3A, CYP1A2 and MATE1: shared by which compounds?
( 4 , 5.2 , 7 ) 7.1 Effect of Other Drugs on PIFELTRO Co-administration of PIFELTRO with a CYP3A inducer decreases doravirine plasma concentrations, which may reduce PIFELTRO efficacy [see Contraindications (4) , Warnings and Precautions (5.2) , and Clinical Pharmacology (12.3) ] .
drug_interactions
Co-administration of PIFELTRO and drugs that are inhibitors of CYP3A may result in increased plasma concentrations of doravirine.
pharmacokinetics
AUC Ratio 1.16 (1.06, 1.26) C max Ratio 1.03 (0.89, 1.19) C 24 Ratio 1.36 (1.19, 1.55) Distribution V dss (L) Based on IV dose 60.5 Plasma Protein Binding 76% Elimination t 1/2 (h) 15 CL/F (mL/min) 106 (35.2) CL renal (mL/min) 9.3 (18.6) Metabolism Primary Pathway(s) CYP3A Excretion Major Route of Elimination Metabolism Urine (unchanged) 6% Biliary/Fecal (unchanged) Minor Specific Populations In…
pharmacokinetics
C 24 =concentration at 24 hours AUC 0-24 (mcg∙h/mL) 16.4 (24) C max (mcg/mL) 1.03 (16) C 24 (mcg/mL) 0.379 (42) Drug Interaction Studies Doravirine is primarily metabolized by CYP3A, and drugs that induce or inhibit CYP3A may affect the clearance of doravirine.
pharmacokinetics
Co-administration of doravirine and drugs that induce CYP3A may result in decreased plasma concentrations of doravirine.
pharmacokinetics
Co-administration of doravirine and drugs that inhibit CYP3A may result in increased plasma concentrations of doravirine.
2 more recorded rows
Interaction statementpharmacokinetics
Doravirine did not inhibit major drug metabolizing enzymes in vitro , including CYPs 1A2, 2B6, 2C8, 2C9, 2C19, 2D6, 3A4, and UGT1A1 and is not likely to be an inducer of CYP1A2, 2B6, or 3A4.
Interaction statementpharmacokinetics
Based on in vitro assays, doravirine is not likely to be an inhibitor of OATP1B1, OATP1B3, P-glycoprotein, BSEP, OAT1, OAT3, OCT2, MATE1, and MATE2K.
Doravirine component of delstrigo, Pifeltro, Pifeltro; with lamivudine and tenofovir disoproxil as Delstrigo, DELSTRIGO COMPONENT DORAVIRINE, IDVYNSO COMPONENT DORAVIRINE, Delstrigo
ChEMBL 37 — CC BY-SA 3.0 Unported · ChEMBL ATC CC BY-SA · ClinicalTrials.gov — US Government work · Open Targets 26.06 — CC0 · mixed register set; per-register licences in docs/specs/corpus-20k-sources.md · openFDA / DailyMed — US Government work
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✓ source coverage passed: 6 source rows
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