This page shows what was measured, who it was measured in, and what that does not settle.
What Dolutegravir does in the body
HIV-1 infection, as part of a combination regimen
HIV cannot survive as a free-floating copy inside a cell. It has to cut into your DNA and paste itself in, and it does that with one enzyme called integrase. Dolutegravir sits in the working part of that enzyme and grabs the two magnesium atoms it needs to make the cut, so the paste step never happens. The viral DNA drifts, gets circularised, and is lost. It does nothing to virus already integrated from before, which is why the drug is taken for life rather than as a course.
What happened in people
88% of 833 treatment-naive patients below 50 copies per millilitre at week 48 against 81% on efavirenz-tenofovir-emtricitabine (P=0.003), with discontinuation for adverse events of 2% against 10%
✎ Source-linked record
Where this came from
A person wrote this into the record with the study named beside it. No reviewer has signed it off.
The recorded finding that sits closest to something a person would notice. Written into the record, not signed off, and it carries no population or interval.
That the weight gained on dolutegravir causes cardiovascular or metabolic disease — no antiretroviral trial has been powered for that endpoint
Where it acts
HIV-1 intasome, in the cytoplasm and nucleus of infected CD4-positive T cells
Kind of result
The kind of result is not recorded
Supervision
RNAWiki has not recorded a supervision or regulatory status for this substance.
What the registries record it as
The substance registry classes this as chemical.
FDA substance registry · DKO1W9H7M1 · read 2026-08-29
Its recorded molecular formula is C20H18F2N3NaO5, weighing 441.36 g/mol.
US prescribing information · 63df5af3-b8ac-4e76-9830-2dbb340af922 · 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 128 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 plasma HIV-1 RNA below 50 copies per millilitre at week 48, FDA snapshot algorithm
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. Mean weight gain of 6.4 kg, 3.2 kg and 1.7 kg across the three arms. Weight was a prespecified safety outcome here but had not been an endpoint in the registration programme, so the signal is visible in this trial and absent from the ones that produced the approval.
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 dispersible tablets for oral suspension for children
Interval reported. Not recorded in this summary
Written into the record, not signed off as a reviewed claim.
Prevalence of neural-tube defects by antiretroviral exposure at conception
✗ The study did not show it
Who was studied
Tsepamo birth-outcome surveillance, Botswana
How many people
119033
Study design
Prospective observational birth-outcome surveillance, not randomised
Compared against
Not recorded for this study
Kind of result
A number that stands in for health
What was found
Difference 0.20 percentage points (95% CI 0.01 to 0.59) in the 2019 report; the updated estimates are 0.10% for dolutegravir against 0.11% for non-dolutegravir exposures
Repeated elsewhere
Failed to Replicate
What this does not prove. A study that did not show an effect does not show that no effect exists anywhere.
The limits of this study, and where it came from
Main limit. This row is here because the first-look estimate of 0.94% changed guidelines in several countries before the denominator grew. `endpoint met: false` records that the association did not hold, not that a trial failed.
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 dispersible tablets for oral suspension for children
Interval reported. 95% CI 0
Written into the record, not signed off as a reviewed claim.
RNAWiki holds 6 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
Dolutegravir
What a person takes: Oral film-coated tablet, and dispersible tablets for oral suspension for children.
The measurement behind this step
Taken once daily with or without food, always with at least two other antiretroviral agents. Polyvalent cations chelate the same triad the drug uses on magnesium, so antacids, iron and calcium supplements interfere with absorption by the drug binding them rather than by any effect on the gut.
Getting in
Swallowed once a day, and it does not need a booster
A single tablet, taken once daily, with or without food. Unlike the protease inhibitors it competes with, it does not need a second drug added purely to slow down its own breakdown.
╌╌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
Absolute bioavailability has not been established; the terminal half-life is roughly 14 hours and clearance is 1.0 L/h. Metabolism is principally UGT1A1 glucuronidation with a minor CYP3A contribution, so no pharmacokinetic booster is required, and the interaction profile is dominated by UGT and CYP3A inducers such as rifampicin rather than by the CYP3A inhibition that defines ritonavir-boosted regimens.
The drug crosses into cells on its own and simply sits there. It has no job until a virus enters that cell, copies its genome into DNA and assembles the machine that will paste it in.
╌╌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
Dolutegravir is passively permeable and distributes into CD4-positive T cells without a transporter. It is not a prodrug and requires no intracellular activation, which distinguishes it sharply from the nucleoside analogues it is co-formulated with, all of which must be phosphorylated three times before they do anything.
It grabs the two magnesium atoms the cutting enzyme needs
Integrase works by holding two magnesium atoms in its active site and using them to make a chemical cut. Dolutegravir clamps onto both of them, so the enzyme is holding the drug instead of the DNA.
╌╌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 carbamoyl pyridone core presents a coplanar triad of oxygen atoms that chelates both catalytic Mg2+ ions in the integrase active site of the intasome, the nucleoprotein complex of integrase tetramer bound to viral DNA ends. Binding requires the intasome to have already formed; the drug has negligible affinity for free integrase.
The 3-prime end of the viral DNA is displaced and cannot attack
With the drug in the way, the prepared end of the viral DNA is pushed out of position. The paste reaction needs that end lined up precisely; it never gets the chance.
╌╌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
Strand transfer is blocked specifically: 3-prime processing, the earlier step in which integrase removes a GT dinucleotide from each viral DNA end, still occurs. The 2,4-difluorobenzyl group occupies the pocket the displaced 3-prime adenosine would fill and stacks against the penultimate cytosine, which is why resistance mutations at Q148, G140 and R263 act by distorting that pocket rather than by blocking the chelating triad.
The viral DNA is never inserted, and the infection stops spreading
Unintegrated viral DNA gets circularised and eventually degraded. The cell survives, no provirus is made, and within weeks plasma virus falls below the level a test can detect.
──Measured in people. Written by a person from the study named beside the step. Not signed off as a reviewed claim.
The measurement behind this step
Unintegrated linear viral DNA is converted to 1-LTR and 2-LTR circles and lost through cell division. In SINGLE the median time to plasma HIV-1 RNA below 50 copies per millilitre was 28 days. The pre-existing reservoir of integrated provirus is untouched, which is why interruption is followed by rebound and why this is suppression rather than cure.
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.
Recommended first-line antiretroviral therapy in the World Health Organization guidelines and in the United States Department of Health and Human Services guidelines, and the integrase inhibitor in the fixed-dose combination with tenofovir and lamivudine that most of the world now takes.
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: “Additional pharmacokinetics data were evaluated in 2 pharmacokinetic substudies in ODYSSEY, an ongoing open-label, randomized, non-inferiority trial to evaluate the safety, efficacy, and pharmacokinetic parameters of TIVICAY or TIVICAY PD plus two NRTIs compared with standard of care in HIV-1–infected pediatric subjects younger than 18 years [see Clinical Pharmacology ( 12.3 )] .”
US prescribing information · 63df5af3-b8ac-4e76-9830-2dbb340af922 · read 2026-08-30
On older people, the label states: “Clinical trials of TIVICAY did not include sufficient numbers of subjects aged 65 and older to determine whether they respond differently from younger subjects.”
US prescribing information · 63df5af3-b8ac-4e76-9830-2dbb340af922 · 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 TIVICAY or TIVICAY PD during pregnancy.”
US prescribing information · 63df5af3-b8ac-4e76-9830-2dbb340af922 · read 2026-08-30
On people who are breastfeeding, the label states: “Risk Summary Dolutegravir is present in human milk.”
US prescribing information · 63df5af3-b8ac-4e76-9830-2dbb340af922 · read 2026-08-30
On people with reduced liver function, the label states: “No clinically important pharmacokinetic differences between subjects with moderate hepatic impairment and matching healthy subjects were observed.”
US prescribing information · 63df5af3-b8ac-4e76-9830-2dbb340af922 · read 2026-08-30
On people with reduced kidney function, the label states: “Dolutegravir plasma concentrations were decreased in subjects with severe renal impairment compared with those in matched healthy controls.”
US prescribing information · 63df5af3-b8ac-4e76-9830-2dbb340af922 · read 2026-08-30
Where the result stopped carrying
The Tsepamo preliminary signal changed treatment guidance for women of childbearing potential across several African countries on the strength of four events in 426 deliveries
Weight gain was not an endpoint in the registration programme and was found by an investigator-led trial afterwards, which is why the label reached the market without it
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.
The product may not be what it says
Contents of a sold product are not always what the label states.
On this record: This is sold as a supplement, so no agency checked what is in a given tub before it was sold.
Other reasons RNAWiki checked and found nothing for (9)
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.
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 dispersible tablets for oral suspension for children
✎ 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, always with at least two other antiretroviral agents.
✎ Source-linked record
Where this came from
A person wrote this into the record with the study named beside it. No reviewer has signed it off.
Recorded notes on how this is sold. The rest of the recorded wording: Polyvalent cations chelate the same triad the drug uses on magnesium, so antacids, iron and calcium supplements interfere with absorption by the drug binding them rather than by any effect on the gut.
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
Hypersensitivity reactions including organ dysfunction and hepatotoxicity are labelled, with higher risk in hepatitis B or C co-infection. Immune reconstitution inflammatory syndrome can follow suppression. Insomnia and headache are the commonest complaints. Serum creatinine rises by a small, non-progressive amount within the first weeks through inhibition of tubular OCT2-mediated creatinine secretion, which is a change in the measurement rather than in glomerular filtration. Weight gain is real, larger than on the drugs it displaced, and of unknown clinical consequence.
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 dispersible tablets for oral suspension for children
✎ Source-linked record
Where this came from
A person wrote this into the record with the study named beside it. No reviewer has signed it off.
The form used in the studies cited on this page.
No source is stored against this line.
What is sold
A recorded note compares this form with the others that are sold. It is kept below, word for word.
§ A fixed RNAWiki sentence
Where this came from
Wording RNAWiki always uses, not a finding about this substance.
The recorded note, unchanged: Polyvalent cations chelate the same triad the drug uses on magnesium, so antacids, iron and calcium supplements interfere with absorption by the drug binding them rather than by any effect on the gut.
No source is stored against this line.
What is recorded as being sold
28 products list this as an active ingredient in the United States drug directory. 22 of them contain it and nothing else.
FDA National Drug Code directory · 58437-027 · read 2026-08-29
They are sold as powder, tablet, film coated and tablet, for suspension, taken oral.
FDA National Drug Code directory · 58437-027 · read 2026-08-29
The regulator's established pharmacologic class for it is hiv integrase inhibitors [moa], human immunodeficiency virus integrase strand transfer inhibitor [epc] and multidrug and toxin extrusion transporter 1 inhibitors [moa].
FDA National Drug Code directory · 58437-027 · read 2026-08-29
5 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 · 806653d1-bf35-4924-b999-ad5d21821cc1 · read 2026-08-29
Those labels are classed as human prescription drug.
US prescribing information · 806653d1-bf35-4924-b999-ad5d21821cc1 · read 2026-08-29
Tivicay is oral at 3 DOSAGE FORMS AND STRENGTHS TIVICAY Tablets: 10 mg: Each tablet contains 10 mg of dolutegravir (as dolutegravir sodium)., recorded as fda label in effect 2025-10-29 in the United States.
US prescribing information · 63df5af3-b8ac-4e76-9830-2dbb340af922 · read 2026-08-30
Evidence carries across two names for one substance. It does not carry across a salt, a mirror form or a mixture.
Evidence on this page does not automatically apply to this one.
What it would be like to take◇Read from sources, not yet reviewed
What you could measure
This one is decided with a clinician, so this section holds questions to ask rather than a plan to run.
RNAWiki could not confidently classify this substance, so no self-experiment plan is offered.
Questions worth asking
Which of the trials of Dolutegravir studied people like me?
What was measured, and for how long?
Was the result a laboratory value or a health outcome?
What would we watch for, and when would we stop?
Tracking can show whether something changed for you. It cannot show what caused it.
RNAWiki records evidence. It does not say whether this substance is right for you.
What is missing or unclear◇Read from sources, not yet reviewed
Claims that go past the evidence
Things said about this substance that sound reasonable, and the exact step that is missing between the evidence and the claim.
✗Goes past the evidence
That the weight gained on dolutegravir causes cardiovascular or metabolic disease — no antiretroviral trial has been powered for that endpoint
Why it sounds right. It follows from something real on this page: a body step, an animal result or a related finding.
The missing step. Nobody measured this in people for this use, or the study that did measure it did not show it.
What would change this
A study in people, for this exact use, measuring this exact thing, that a reviewer signs off.
RNAWiki has not yet published a reviewed conclusion for this use.
✗Goes past the evidence
That dolutegravir carries the same resistance barrier in integrase-experienced patients as it demonstrated in integrase-naive ones
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 2018 neural-tube defect estimate of 0.94% described a real excess risk — the same surveillance programme now reports 0.10% against 0.11% for other regimens
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 Dolutegravir 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.
SINGLE: 88% suppressed at 48 weeks against 81% on the standard of its day
In plain words
In 833 people who had never been treated for HIV, dolutegravir plus abacavir and lamivudine suppressed the virus in 88% at 48 weeks, against 81% for the then-standard three-drug tablet. Nobody in the dolutegravir arm developed resistance.
What was measured
Proportion with plasma HIV-1 RNA below 50 copies per millilitre at week 48, FDA snapshot algorithm
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
SINGLE (NCT01263015) randomised 844 treatment-naive adults, of whom 833 received at least one dose, to dolutegravir 50 mg once daily with abacavir-lamivudine or to fixed-dose efavirenz-tenofovir disoproxil-emtricitabine. At week 48, 88% of the dolutegravir group had HIV-1 RNA below 50 copies per millilitre against 81% of the comparator group (P=0.003). Median time to suppression was 28 days against 84 days (P<0.001) and the mean CD4 increase was 267 against 208 cells per cubic millimetre (P<0.001). Discontinuation for adverse events was 2% against 10%. No participant in the dolutegravir group had detectable antiviral resistance; in the comparator group one tenofovir-associated and four efavirenz-associated mutations were detected.
Written into the record, not signed off as a reviewed claim
SAILING: superior to raltegravir, with a quarter of the emergent resistance
In plain words
Head to head against the first integrase inhibitor in 715 treatment-experienced patients, dolutegravir suppressed more people and, more importantly, far fewer of the failures carried a new integrase mutation.
What was measured
Virological suppression at week 48 and the count of failures carrying treatment-emergent integrase resistance
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
SAILING (NCT01231516) randomised 715 antiretroviral-experienced, integrase-inhibitor-naive adults to dolutegravir 50 mg once daily or raltegravir 400 mg twice daily with investigator-selected background therapy. At week 48, 251 of the dolutegravir patients (71%) had HIV-1 RNA below 50 copies per millilitre against 230 of the raltegravir patients (64%), adjusted difference 7.4% (95% CI 0.7 to 14.2), and superiority was concluded (p=0.03). Virological failure with treatment-emergent integrase-inhibitor resistance occurred in four dolutegravir patients against seventeen on raltegravir, adjusted difference -3.7% (95% CI -6.1 to -1.2, p=0.003).
Written into the record, not signed off as a reviewed claim
The neural-tube defect signal: 0.94% in 2018, 0.30% in 2019, indistinguishable from background by 2025
In plain words
In 2018 a birth-outcome survey in Botswana reported four neural-tube defects among 426 babies conceived on dolutegravir, a rate roughly eight times the usual one. It changed guidelines across Africa overnight. As the same study kept counting, the rate fell to 0.30%, then to 0.10%, against 0.11% for every other regimen. The signal was real as a measurement and wrong as a conclusion.
What was measured
That dolutegravir at conception raises the risk of neural-tube defects — an inference from four events in a first-look surveillance dataset that its own continued follow-up did not sustain
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
Zash and colleagues reported the preliminary Tsepamo signal in a 2018 correspondence to the New England Journal of Medicine: four neural-tube defects among 426 deliveries to women on dolutegravir from conception, a prevalence of 0.94% against 0.12% in non-dolutegravir exposures. The 2019 full report covered 119,033 deliveries and found five defects among 1,683 dolutegravir-at-conception deliveries (0.30%) against fifteen among 14,792 non-dolutegravir-at-conception deliveries (0.10%), a difference of 0.20 percentage points (95% CI 0.01 to 0.59); efavirenz at conception was 0.04% and HIV-uninfected mothers 0.08%. A 2025 retrospective in AIDS reports the updated Tsepamo estimates as 0.10% for dolutegravir and 0.11% for non-dolutegravir exposures, and states that the early finding had been statistically compatible with a wide range of effect sizes including no difference.
Written into the record, not signed off as a reviewed claim
Weight gain on dolutegravir is measured; that it causes metabolic disease is not measured
In plain words
People starting dolutegravir gain more weight than people starting the drugs it replaced, and the trials show that clearly. Whether that weight translates into diabetes, heart attacks or strokes has not been tested, because no antiretroviral trial has ever been powered for those outcomes.
What was measured
That the weight gained on dolutegravir-based therapy causes cardiovascular or metabolic disease — plausible, mechanistically coherent, and untested by any powered endpoint
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
ADVANCE (NCT03122262), a 1,053-patient investigator-led trial in South Africa, found mean weight increases at week 48 of 6.4 kg on dolutegravir with emtricitabine and tenofovir alafenamide, 3.2 kg on dolutegravir with emtricitabine and tenofovir disoproxil, and 1.7 kg on standard-care efavirenz-tenofovir disoproxil-emtricitabine, while virological outcomes were noninferior at 84%, 85% and 79%. NAMSAL reported the same direction in Cameroon and, by week 192, mean gains of 9.4 kg on dolutegravir against 5.9 kg on low-dose efavirenz. A North American cohort found 6.0 kg gained at 18 months on dolutegravir against 2.6 kg on non-nucleoside regimens (P<0.05). A prespecified secondary analysis of ADVANCE then found that blood-pressure rises tracked change in BMI rather than the regimen or kidney function, with the largest 96-week systolic increase 1.7 mmHg. So the weight is measured and its proximate consequence on blood pressure is measured; the cardiovascular endpoint that would matter is not.
Written into the record, not signed off as a reviewed claim
No treatment-emergent integrase resistance in any treatment-naive registration trial
In plain words
Across the trials that got dolutegravir approved for people starting treatment for the first time, not one person who failed on it developed a mutation that made integrase inhibitors stop working. That is rare and it is the reason the drug is used the way it is.
What was measured
Count of virological failures carrying treatment-emergent integrase-inhibitor resistance mutations
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
In SPRING-2 (NCT01227824), 822 treatment-naive adults were randomised to dolutegravir once daily or raltegravir twice daily; 361 dolutegravir patients (88%) and 351 raltegravir patients (85%) reached HIV-1 RNA below 50 copies per millilitre at week 48, adjusted difference 2.5% (95% CI -2.2 to 7.1). No treatment-emergent resistance was seen in dolutegravir patients with virological failure, whereas one raltegravir failure carried treatment-emergent integrase resistance. SINGLE reported the same absence of resistance in its dolutegravir arm, and ADVANCE reported no integrase-inhibitor resistance across 1,053 patients. The property behind this is kinetic rather than thermodynamic: dolutegravir dissociates from the intasome slowly enough that a mutant with reduced binding still loses more replicative fitness than it gains.
Written into the record, not signed off as a reviewed claim
The resistance barrier is a naive-population finding read across to experienced ones
In plain words
Dolutegravir almost never fails with resistance in people starting treatment for the first time. In people who already carry integrase mutations from an earlier drug, it does fail with resistance, and the two situations get spoken about as though they were one.
What was measured
That dolutegravir has the same resistance barrier in integrase-experienced patients that it demonstrated in integrase-naive ones
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
The FDA-approved label restricts the paediatric indication to integrase-inhibitor-naive patients, and SAILING enrolled only integrase-inhibitor-naive adults; its four treatment-emergent resistance cases arose in that population. Salvage use in patients with pre-existing raltegravir or elvitegravir resistance is a separate clinical situation with a separate dosing schedule and a materially different failure rate, and the trials that studied it were single-arm. The general claim that dolutegravir has a high genetic barrier is well supported where it was measured. Extending it to a patient who already carries Q148 plus secondary mutations is an inference the registration programme did not test.
Written into the record, not signed off as a reviewed claim
NAMSAL: the margin over efavirenz narrows when efavirenz is dosed properly
In plain words
A trial in Cameroon compared dolutegravir with a lower 400 mg dose of efavirenz rather than the usual 600 mg. Dolutegravir still won, but by five points rather than the seven points seen against the older regimen, and the efavirenz arm gained less weight.
What was measured
Proportion below 50 copies per millilitre at weeks 48 and 192, and mean weight change
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
NAMSAL ANRS 12313 (NCT02777229) randomised 613 evaluable treatment-naive adults in Yaounde to dolutegravir or efavirenz 400 mg, each with tenofovir disoproxil and lamivudine. At week 48, 231 of 310 in the dolutegravir group (74.5%) and 209 of 303 in the efavirenz 400 group (69.0%) had a viral load below 50 copies per millilitre, meeting noninferiority. Virological failure occurred in 3 dolutegravir recipients against 16 efavirenz recipients. By week 192 suppression was 69% against 62%, with mean weight gains of 9.4 kg against 5.9 kg.
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What is not here
7 questions this page could not answer
These sections were prepared and left out because there was nothing to put in them. They are listed rather than hidden, so the gaps in this record are visible.
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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.
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The record as stored
The full record, for auditing
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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.
An integrase strand-transfer inhibitor that jams the enzyme HIV uses to paste itself into human DNA; it suppressed virus in 88% of untreated patients at 48 weeks against 81% on the previous standard in SINGLE, and it has never selected resistance in a treatment-naive trial, which is why it became first-line almost everywhere.
Recorded evidence blocks (10)
Q1
On the Dolutegravir label: indicated for what?
"TIVICAY and TIVICAY PD are indicated in combination with other antiretroviral agents for the treatment of HIV‑1 infection in adults (treatment-naïve or -experienced) and in pediatric patients (treatment-naïve or -experienced but integrase strand transfer inhibitor [INSTI]-naïve) aged at least 4 weeks and weighing at…": indications and usage on Dolutegravir's label. DailyMed label · 485bc9db-8665-9f5a-e063-6394a90a7921 · 2026-05-22
Q2
166 registered trials of Dolutegravir — at which phases?
Registered studies posting no result
116 of 166
166 registered studies of Dolutegravir: 56 phase1, 34 phase3, 33 phase2, 30 phase4, 16 na or unstated, 6 na, 2 early phase1. CLINICALTRIALS_SNAPSHOT · 2026-09-01
357 with a PubMed record
Show the evidence
phase1
56
phase3
34
phase2
33
phase4
30
na or unstated
16
na
6
9 more recorded rows
early phase1
2
completed
120
unknown
14
recruiting
10
terminated
10
active not recruiting
4
withdrawn
4
not yet recruiting
3
no longer available
1
recorded 2026-09-01 · last checked 2026-09-04
Q3
13 of Dolutegravir's trials stopped: safety, futility/efficacy, accrual/recruitment, other?
safety (3), futility/efficacy (1), accrual/recruitment (3) and other (6): Dolutegravir's stop wording, clustered. CLINICALTRIALS_SNAPSHOT · 2026-09-01
"In a Phase II study in HIV-infected patients there were a number of seizures, although exact causality could not be assessed phase 1 activity was terminated."; 13 of 166 registered studies
Show the evidence
Trial
NCT01283100
withdrawn; "In a Phase II study in HIV-infected patients there were a number of seizures, although exact causality could not be assessed phase 1 activity was terminated."
NCT02386098
terminated; "GI Intolerability"
NCT02566707
terminated; "due to introduction of another integrase inhibitor, recruitement was not feasible anymore."
NCT02596334
terminated; "5 patients on tivicay had virological failure"
NCT02659761
terminated; "Sponsor decision due to slow recruitment rates and no future recruitment foreseen"
NCT02924389
terminated; "This study terminated early due to the ongoing covid-19 pandemic making it unsafe to recruit participants for in-person visits. Participants are living with HIV who are antiretroviral therapy-naive and are at high risk of COVID-19…"
7 further recorded trials
NCT03813979
withdrawn; "difficult recruitment and delay due to COVID19"
NCT04183738
withdrawn; "In the context of COVID-19 pandemic."
NCT04272242
terminated; "Opening of Arm 2 was dependent upon assessment of DTG pharmacokinetics (PK) data from participants in Arm 1. Arm 1 is complete and results are reported. Arm 2 was not conducted based on the Arm 1 PK assessment."
NCT04493216
terminated; "Company decision to stop compound development. The decision is not based on any safety or efficacy concerns. It reflects the company strategy for portfolio progression."
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."
NCT04900038
terminated; "Company decision to stop compound development. The decision was not based on any safety or efficacy concerns. It reflected the company strategy for portfolio progression."
NCT05193994
terminated; "A planned interim analysis resulted in the recommendation that the trial be stopped. The results showed no benefit of Triumeq for people with ALS compared with placebo on survival, the primary outcome measure."
recorded 2026-09-01 · last checked 2026-09-04
Q4
Human studies of Dolutegravir used GSK1349572 250 mg — over how long?
Human studies of Dolutegravir used "GSK1349572 250 mg". ClinicalTrials.gov · 2026-09-01
20 recorded entries; human; tablet, oral; also "GSK1349572 50mg QD and TPV/RTV 500/200mg BID x 5 days", "Dolutegravir 50 mg", "Dolutegravir 50 mg/abacavir 600 mg/lamivudine 300 mg"
Show the evidence
human
NCT00996021
GSK1349572 250 mg
NCT01068925
GSK1349572 50mg QD and TPV/RTV 500/200mg BID x 5 days
Dolutegravir's half-life is 14 hours — which schedules were studied?
14 hours, the half-life Dolutegravir's label states: "Elimination Dolutegravir has a terminal half-life of approximately 14 hours and an apparent clearance (CL/F) of 1.0 L/h based on population pharmacokinetic analyses." DailyMed label · 485bc9db-8665-9f5a-e063-6394a90a7921 · 2026-05-22
tmax 1 to 3 hours.
Show the evidence
half lifepharmacokinetics
14 hours; Elimination Dolutegravir has a terminal half-life of approximately 14 hours and an apparent clearance (CL/F) of 1.0 L/h based on population pharmacokinetic analyses.
tmaxpharmacokinetics
1 to 3 hours; Absorption Following oral administration of dolutegravir, peak plasma concentrations were observed 1 to 3 hours postdose.
metabolismpharmacokinetics
Metabolism: Dolutegravir is primarily metabolized via UGT1A1 with some contribution from CYP3A.
recorded 2026-05-22 · last checked 2026-09-04
Q6
Which 74 trials of Dolutegravir posted no result?
Posted no result
74 of 74 completed trials
Registrations
NCT00555035, NCT00631592, NCT00774111, NCT00774735, NCT00858455 and NCT00867152, and 68 more
Completion dates
oldest 2008-02; newest 2024-02-07
Show the evidence
Trial
NCT00555035
2008-02
NCT00631592
2008-06
NCT00774111
2008-12
NCT00774735
2008-12
NCT00858455
2009-03
NCT00867152
2009-05
14 further recorded trials
NCT00883935
2009-06
NCT00942136
2009-09
NCT00996021
2009-12
NCT01068925
2010-04-05
NCT01098526
2010-05-26
NCT01209065
2010-11
NCT01214993
2010-11
NCT01332565
2011-06
NCT01231529
2011-06-04
NCT01366547
2011-07
NCT01382238
2011-08
NCT01425099
2011-10
NCT01231542
2011-12
NCT01467518
2012-02
Q7
At the median, Dolutegravir's trials enrolled 50 people — anything larger?
Median enrolment
50
Largest enrolment
2500
Registered trials counted
165
Q8
What do 7814 spontaneous reports say about Dolutegravir — 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.
Dolutegravir appears in spontaneous reports to regulators. Across the 10 most-reported reaction terms, 7814 reaction mentions were counted: drug resistance 1332; virologic failure 1307; viral mutation identified 1161; pathogen resistance 1081. FAERS via Open Targets · CHEMBL1213165 · 2026-06-24
Show the evidence
drug resistance
1332
virologic failure
1307
viral mutation identified
1161
pathogen resistance
1081
abortion spontaneous
580
treatment failure
559
4 more recorded rows
anaemia
550
premature baby
464
immune reconstitution inflammatory syndrome
449
lipodystrophy acquired
331
recorded 2026-06-24 · last checked 2026-09-04
Q9
Which 10 reactions does Dolutegravir's label not list?
( 7.3 ) 7.1 Effect of Dolutegravir on the Pharmacokinetics of Other Agents In vitro, dolutegravir inhibited the renal organic cation transporters, OCT2 (IC 50 = 1.93 microM) and multidrug and toxin extrusion transporter (MATE) 1 (IC 50 = 6.34 microM).
drug_interactions
In vivo, dolutegravir inhibits tubular secretion of creatinine by inhibiting OCT2 and potentially MATE1.
drug_interactions
Dolutegravir may increase plasma concentrations of drugs eliminated via OCT2 or MATE1 (dofetilide, dalfampridine, and metformin, Table 8 ) [see Contraindications ( 4 ), Drug Interactions ( 7.3 )] .
drug_interactions
In vitro, dolutegravir inhibited the basolateral renal transporters, organic anion transporter (OAT) 1 (IC 50 = 2.12 microM) and OAT3 (IC 50 = 1.97 microM).
drug_interactions
However, in vivo, dolutegravir did not alter the plasma concentrations of tenofovir or para-amino hippurate, substrates of OAT1 and OAT3.
drug_interactions
In vitro, dolutegravir did not inhibit (IC 50 greater than 50 microM) the following: cytochrome P450 (CYP)1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP3A, uridine diphosphate glucuronosyltransferase (UGT)1A1, UGT2B7, P-glycoprotein (P-gp), breast cancer resistance protein (BCRP), bile salt export pump (BSEP), organic anion transporter polypeptide (OATP)1B1, OATP1B3, OCT1, multidrug…
2 more recorded rows
Interaction statementdrug_interactions
In vitro, dolutegravir did not induce CYP1A2, CYP2B6, or CYP3A4.
Interaction statementdrug_interactions
7.2 Effect of Other Agents on the Pharmacokinetics of Dolutegravir Dolutegravir is metabolized by UGT1A1 with some contribution from CYP3A.
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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