This page shows what was measured, who it was measured in, and what that does not settle.
What Cabotegravir does in the body
HIV prevention, and HIV-1 treatment as maintenance therapy
HIV cannot survive inside a cell as a loose copy. It has to paste a DNA version of itself into one of your chromosomes, and it uses one enzyme to do that. Cabotegravir grips the two magnesium atoms that enzyme needs to make the cut, so the paste step never happens and the virus never establishes itself. The difference from a tablet is not chemical but physical: injected into muscle as a suspension of crystals, it dissolves slowly enough that one injection covers two months.
What happened in people
HIV incidence 0.41 against 1.22 per 100 person-years in 4,566 men who have sex with men and transgender women, hazard ratio 0.34 (95% CI 0.18 to 0.62)
✎ 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.
The first HIV prevention that is not a daily tablet, and the first prevention agent with randomised superiority over the existing standard in both men and women
Where it acts
HIV-1 intasome in CD4-positive T cells; the gluteal muscle acts as the depot from which the drug is released for months
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 · HMH0132Z1Q · read 2026-08-29
Its recorded molecular formula is C19H17F2N3O5, weighing 405.35 g/mol.
US prescribing information · 4338428e-43d4-4e02-ac9d-bd98e738a7da · 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.
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.
Incident HIV infection, long-acting cabotegravir every eight weeks against daily oral tenofovir disoproxil-emtricitabine
✓ The study showed what it set out to show
Who was studied
HPTN 083 (NCT02720094)
How many people
4566
Study design
Phase 2b/3, randomised, double-blind, double-dummy, stopped early for efficacy at the first preplanned interim analysis
Compared against
Not recorded for this study
Kind of result
A number that stands in for health
What was found
13 versus 39 infections, incidence 0.41 versus 1.22 per 100 person-years, hazard ratio 0.34 (95% CI 0.18 to 0.62)
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. Breakthrough infections carried integrase inhibitor resistance and delayed detection. The published conclusion asks for strategies to prevent that resistance, which is a registration trial naming its own unsolved problem.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Extended-release intramuscular nanocrystal suspension, given gluteally, with an oral tablet formulation used as a lead-in and as oral bridging
Interval reported. 95% CI 0
Written into the record, not signed off as a reviewed claim.
4 versus 36 infections, 0.20 versus 1.85 per 100 person-years, hazard ratio 0.12 (95% CI 0.05 to 0.31), p<0.0001
Repeated elsewhere
Replicated
What this does not prove. Meeting one endpoint in one population does not carry to other goals or other people.
The limits of this study, and where it came from
Main limit. Injection coverage was 93% of person-years while only 42.1% of sampled plasma in the oral arm had tenofovir concentrations consistent with daily use, so part of the measured difference is delivery rather than pharmacology.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Extended-release intramuscular nanocrystal suspension, given gluteally, with an oral tablet formulation used as a lead-in and as oral bridging
Interval reported. 95% CI 0
Written into the record, not signed off as a reviewed claim.
Prospective diagnostic-accuracy analysis within an open-label extension
Compared against
Not recorded for this study
Kind of result
A number that stands in for health
What was found
Diagnostic delay 7% versus 47% (p=0.02), treatment initiation median 15 versus 62 days (p=0.02); sensitivity 93%, specificity 99.92%, positive predictive value 55% overall and 29% within six months of an injection
Repeated elsewhere
Unreplicated
What this does not prove. Meeting one endpoint in one population does not carry to other goals or other people.
The limits of this study, and where it came from
Main limit. Some false-positive RNA results led to delay or discontinuation of injections in people who did not have HIV. Resistance was less frequent with RNA screening, 15% against 31%, but not significantly so (p=0.22).
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Extended-release intramuscular nanocrystal suspension, given gluteally, with an oral tablet formulation used as a lead-in and as oral bridging
Interval reported. Not recorded in this summary
Written into the record, not signed off as a reviewed claim.
Proportion with HIV-1 RNA at or above 50 copies per millilitre at week 48 by FDA snapshot, monthly injectable cabotegravir with rilpivirine against continued oral therapy
✓ The study showed what it set out to show
Who was studied
Pooled ATLAS (NCT02951052) and FLAIR (NCT02938520), week 48
How many people
1182
Study design
Two randomised, open-label, multicentre phase 3 switch trials, pooled
Compared against
Not recorded for this study
Kind of result
A number that stands in for health
What was found
Non-inferiority met against a 4% margin for the primary and key secondary endpoints
Repeated elsewhere
Replicated
What this does not prove. Meeting one endpoint in one population does not carry to other goals or other people.
The limits of this study, and where it came from
Main limit. Seven confirmed virological failures in each arm, with resistance-associated mutations in 6 of 7 long-acting failures against 3 of 7 on oral therapy. Injection site reactions in 83% of long-acting recipients.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Extended-release intramuscular nanocrystal suspension, given gluteally, with an oral tablet formulation used as a lead-in and as oral bridging
Interval reported. Not recorded in this summary
Written into the record, not signed off as a reviewed claim.
RNAWiki holds 4 written-up human studies for this substance, each with the question it asked.
How we know it
Each card names the study, the number of people and what the study set out to measure.
What this does not prove
These summaries were written by a person and have not been signed off as reviewed claims.
Why it matters
A study that failed is as informative as one that worked, and both are here.
What we still do not know
No reviewed claim exists, so no exact population, effect size or interval is published yet.
What it changes in the body◇Read from sources, not yet reviewed
The path through the body
From what a person takes to what changes. A solid line is a step measured in people. A dashed line is a step nobody has measured that way.
Start
Cabotegravir
What a person takes: Extended-release intramuscular nanocrystal suspension, given gluteally, with an oral tablet formulation used as a lead-in and as oral bridging.
The measurement behind this step
The prevention product is given as an injection every two months after an initiation interval; the treatment regimen is given with rilpivirine monthly or two-monthly. An oral lead-in is used before treatment injections so that tolerability is established before a depot is created. Rifampicin and rifapentine are contraindicated because UGT1A1 induction lowers exposure below the protective range, and a depot cannot be dose-adjusted after it has been placed.
Getting in
Injected into muscle as a suspension of crystals
Not swallowed. A milky suspension of tiny drug crystals is injected into the buttock, where it forms a deposit that the body dissolves slowly over the following weeks.
╌╌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 product is a nanocrystal suspension produced by wet bead milling with a surfactant stabiliser. Release is dissolution-rate-limited rather than metabolism-limited, so the apparent terminal half-life after intramuscular injection is on the order of months, and drug remains detectable for a year or more after the final dose. An oral lead-in is used before treatment injections to establish tolerability before committing a month of drug to a depot that cannot be withdrawn.
It circulates and enters cells, and simply waits there
The drug moves out of the deposit into the blood, then into cells, where it does nothing at all unless a virus arrives.
╌╌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
Cabotegravir is passively permeable, distributes into CD4-positive T cells without a transporter, and requires no intracellular activation. It is cleared principally by UGT1A1 glucuronidation with a minor UGT1A9 contribution, so no pharmacokinetic booster is required and the interaction profile is dominated by UGT inducers, principally rifampicin, which is contraindicated.
It grabs the two magnesium atoms the cutting enzyme needs
When a virus does enter and copies its genome into DNA, it assembles the machine that will paste that DNA into a chromosome. Cabotegravir clamps onto the two magnesium atoms that machine uses to make the cut.
╌╌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 oxygen triad that chelates both catalytic Mg2+ ions in the integrase active site of the assembled intasome, with the 2,4-difluorobenzyl group occupying the pocket vacated by the displaced 3-prime adenosine. Binding requires the intasome to have formed; affinity for free integrase is negligible.
The paste step never happens, so infection is never established
Without integration there is no permanent copy. In prevention this means the virus that arrives never gets established at all, which is a different and better outcome than suppressing one that already is.
╌╌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 while 3-prime processing still occurs. Unintegrated viral DNA is circularised and lost. In prevention this interrupts the establishment of the reservoir rather than suppressing an existing one, which is why prophylaxis protects rather than merely controls. Escape at Q148 and N155 requires accumulating substitutions that cost replicative fitness, which is the resistance barrier the second-generation drugs are built around.
And the depot empties slowly, which is the benefit and the risk in one property
Two months of protection from one injection is the point. The same slow release means that if protection ever does fail, the virus grows for months in the presence of a little drug, which is the situation that teaches it to resist.
──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
A nested case-control analysis found that minimum plasma cabotegravir at or above four times the protein-adjusted 90% inhibitory concentration gave a 93% reduction in acquisition risk against concentrations below one times that threshold, and that only 26% of people who acquired HIV had reached it against 76% of matched controls. Breakthrough infections in HPTN 083 carried integrase resistance and delayed detection. The pharmacokinetic tail is a single property with opposite consequences on either side of the protective threshold.
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 at risk of sexually acquired HIV who receive an injection every two months, and virologically suppressed people who have switched their treatment from daily tablets to injections of cabotegravir with rilpivirine.
Who is missing from the studies
Which groups were under-represented in the studies has not been recorded for this substance. Pregnancy, breastfeeding, children, older adults, and people with liver or kidney conditions are commonly excluded from trials; nothing here says whether they were.
What the label states about particular groups
On pediatric, the label states: “APRETUDE for HIV-1 PrEP was evaluated in 2 open-label multicenter clinical trials, HPTN 083-01 and HPTN 084-01, in adolescent individuals 12 to less than 18 years of age weighing at least 35 kg who are at risk for HIV-1 acquisition.”
US prescribing information · 4338428e-43d4-4e02-ac9d-bd98e738a7da · read 2026-08-30
On older people, the label states: “No dose adjustment is required in elderly individuals.”
US prescribing information · 4338428e-43d4-4e02-ac9d-bd98e738a7da · 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 APRETUDE during pregnancy.”
US prescribing information · 4338428e-43d4-4e02-ac9d-bd98e738a7da · read 2026-08-30
On people who are breastfeeding, the label states: “Risk Summary There are no data on the presence of cabotegravir in human milk.”
US prescribing information · 4338428e-43d4-4e02-ac9d-bd98e738a7da · read 2026-08-30
On people with reduced liver function, the label states: “Based on studies with oral cabotegravir, no dosage adjustment of APRETUDE is necessary for individuals with mild or moderate hepatic impairment (Child-Pugh A or B).”
US prescribing information · 4338428e-43d4-4e02-ac9d-bd98e738a7da · read 2026-08-30
On people with reduced kidney function, the label states: “Based on studies with oral cabotegravir, no dosage adjustment of APRETUDE is necessary for individuals with mild (creatinine clearance ≥60 to <90 mL/min), moderate (creatinine clearance ≥30 to <60 mL/min) or severe renal impairment (creatinine clearance ≥15 to <30 mL/min) [see Clinical Pharmacology ( 12.3 )] .”
US prescribing information · 4338428e-43d4-4e02-ac9d-bd98e738a7da · read 2026-08-30
Where the result stopped carrying
Breakthrough infections during prophylaxis carried integrase inhibitor resistance and delayed detection, and the registration paper closes by asking the field for strategies to prevent it
The proposed remedy, RNA screening at every visit, has a positive predictive value of 29% within six months of an injection, and its false positives caused injections to be delayed or stopped in people without HIV
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
Given by a clinician
❝ Quoted from a source
Where this came from
Copied from a source RNAWiki stored, with the source named.
Read from the recorded approval status.
No source is stored against this line.
Form and route
Extended-release intramuscular nanocrystal suspension, given gluteally, with an oral tablet formulation used as a lead-in and as oral bridging
✎ Source-linked record
Where this came from
A person wrote this into the record with the study named beside it. No reviewer has signed it off.
The form and route recorded on this substance.
No source is stored against this line.
Who oversees it
RNAWiki has not recorded a supervision or regulatory status for this substance.
❝ Quoted from a source
Where this came from
Copied from a source RNAWiki stored, with the source named.
No register row and no identity class settled the question.
No source is stored against this line.
What is in the pack
The prevention product is given as an injection every two months after an initiation interval; the treatment regimen is given with rilpivirine monthly or two-monthly. An oral lead-in is used before treatment injections so that tolerability is established before a depot is created. Rifampicin and rifapentine are contraindicated because UGT1A1 induction lowers exposure below the protective range, and a depot cannot be dose-adjusted after it has been placed.
✎ 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
Injection site reactions are the dominant adverse event, reported in 81.4% of recipients in HPTN 083 and 38.0% in HPTN 084, decreasing in frequency over time and rarely leading to discontinuation. Hepatotoxicity and hypersensitivity reactions are labelled. The distinctive risks are structural rather than toxicological: drug persists for a year or more after the last injection, so acquiring HIV during that decline risks integrase resistance, and HIV testing is required before every injection. Depressive disorders including suicidal ideation are labelled for the treatment regimen.
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
Extended-release intramuscular nanocrystal suspension, given gluteally, with an oral tablet formulation used as a lead-in and as oral bridging
✎ 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
An oral lead-in is used before treatment injections so that tolerability is established before a depot is created. Rifampicin and rifapentine are contraindicated because UGT1A1 induction lowers exposure below the protective range, and a depot cannot be dose-adjusted after it has been placed.
✎ 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
8 products list this as an active ingredient in the United States drug directory. 8 of them contain it and nothing else.
FDA National Drug Code directory · 52482-018 · read 2026-08-29
They are sold as powder and tablet, film coated, taken oral.
FDA National Drug Code directory · 52482-018 · 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 organic anion transporter 1 inhibitors [moa].
FDA National Drug Code directory · 52482-018 · read 2026-08-29
2 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 · 4338428e-43d4-4e02-ac9d-bd98e738a7da · read 2026-08-29
Those labels are classed as human prescription drug.
US prescribing information · 4338428e-43d4-4e02-ac9d-bd98e738a7da · read 2026-08-29
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 Cabotegravir 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 superiority over daily oral prophylaxis reflects greater intrinsic antiviral protection rather than the difference between an administered drug and a self-taken one
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 excess of resistance among long-acting failures is caused by the depot tail rather than by chance in small event counts, in prevention or in treatment
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 better bone mineral density over 105 weeks means fewer fractures, which no prevention trial has been powered to test
Why it sounds right. It follows from something real on this page: a body step, an animal result or a related finding.
The missing step. Nobody measured this in people for this use, or the study that did measure it did not show it.
What would change this
A study in people, for this exact use, measuring this exact thing, that a reviewer signs off.
RNAWiki has not yet published a reviewed conclusion for this use.
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 Cabotegravir 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.
HPTN 083: 13 infections against 39, and the trial was stopped at the first interim look
In plain words
In 4,566 men who have sex with men and transgender women, injections every eight weeks produced 13 HIV infections against 39 on the daily tablet. The independent review board stopped the trial early at its first scheduled interim analysis.
What was measured
Incident HIV infection: 0.41 against 1.22 per 100 person-years, hazard ratio 0.34 (95% CI 0.18 to 0.62)
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
HPTN 083 (NCT02720094) was a randomised, double-blind, double-dummy non-inferiority trial comparing long-acting cabotegravir 600 mg intramuscularly every eight weeks with daily oral tenofovir disoproxil-emtricitabine, with participants followed for 153 weeks. The intention-to-treat population was 4,566, of whom 570 (12.5%) identified as transgender women, median age 26. Among 1,698 United States participants, 845 (49.8%) identified as Black. Incident HIV infection occurred in 52 participants: 13 in the cabotegravir group, incidence 0.41 per 100 person-years, against 39 in the oral group, incidence 1.22 per 100 person-years, hazard ratio 0.34 (95% CI 0.18 to 0.62). The trial was stopped early for efficacy on the first preplanned interim analysis, and the effect was consistent across prespecified subgroups. Injection-site reactions were reported in 81.4% of the cabotegravir group against 31.3% of the oral group, the latter reflecting the double-dummy placebo injections.
Written into the record, not signed off as a reviewed claim
HPTN 084: 4 infections against 36 in women, a hazard ratio of 0.12
In plain words
In 3,224 women across seven countries in sub-Saharan Africa, four women in the injection group acquired HIV against thirty-six on the daily tablet. This is the population in which two earlier prevention trials had reported no effect at all.
What was measured
Incident HIV infection in women: 0.20 against 1.85 per 100 person-years, hazard ratio 0.12 (95% CI 0.05 to 0.31)
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
HPTN 084 (NCT03164564) was a phase 3, randomised, double-blind, double-dummy, active-controlled superiority trial at 20 sites in seven countries in sub-Saharan Africa, enrolling 3,224 participants assigned female sex at birth, aged 18 to 45, median age 25. Forty incident infections occurred over 3,898 person-years, overall incidence 1.0% (95% CI 0.73 to 1.40): four in the cabotegravir group, 0.2 per 100 person-years (95% CI 0.06 to 0.52), and 36 in the oral group, 1.85 per 100 person-years (1.3 to 2.57), hazard ratio 0.12 (95% CI 0.05 to 0.31), p<0.0001, risk difference -1.6%. Injection coverage was 93% of total person-years. Injection site reactions were more frequent in the cabotegravir group, 577 of 1,519 (38.0%) against 162 of 1,516 (10.7%), and did not lead to injection discontinuation. Confirmed pregnancy incidence was 1.3 per 100 person-years and no congenital anomalies were reported.
Written into the record, not signed off as a reviewed claim
The registration paper ends by asking the field to solve its own failure mode
In plain words
When someone acquires HIV despite the injections, two things go wrong at once. The diagnosis is delayed because the drug suppresses the virus enough to blunt the tests, and the virus that emerges has usually developed integrase resistance because it grew up in a long stretch of not-quite-enough drug.
What was measured
Integrase inhibitor resistance and delayed HIV detection among breakthrough infections, reported in the primary trial publication
Effect estimate
No reviewed effect estimate exists for this record.
Limits
This entry records a failure.
From the source
The HPTN 083 results section states that in participants in whom HIV infection was diagnosed after exposure to long-acting cabotegravir, integrase strand-transfer inhibitor resistance and delays in the detection of HIV infection were noted. The conclusion states, in its own words, that strategies are needed to prevent integrase resistance in cases of cabotegravir prevention failure. The mechanism is the pharmacokinetic tail: drug released from an intramuscular depot declines over months, so a person who acquires HIV during that decline spends an extended period at concentrations too low to suppress and high enough to select. That is the mirror image of an oral drug, whose concentrations fall through the same range in a day. This is not an incidental safety note; it is the principal unresolved problem of long-acting prevention, identified in the trial that established the approach.
Written into the record, not signed off as a reviewed claim
The proposed fix works and brings a new problem: RNA screening halved delays and false-positived at 45%
In plain words
Adding a viral RNA test at every visit cut diagnostic delays from 47% of cases to 7% and got people onto treatment forty-seven days sooner. But nearly half the positive RNA results were wrong, and within six months of an injection more than seven in ten were wrong, which caused injections to be delayed or stopped in people who did not have HIV.
What was measured
Diagnostic delay in 7% against 47% of cases, treatment initiation at median 15 against 62 days, positive predictive value 55% overall and 29% within six months of an injection
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
In the open-label extension of HPTN 083, sites performed rapid, antigen/antibody and HIV RNA testing at every visit. RNA screening was associated with fewer diagnostic delays, 7% against 47% of cases (p=0.02), and earlier treatment initiation, median 15 against 62 days (p=0.02). Drug resistance was less frequent with RNA screening, 15% against 31% of cases, but this did not reach significance (p=0.22). Five cases were first detected by RNA testing alone. Sensitivity was 93% (95% CI 76 to 99) and specificity 99.92% (95% CI 99.88 to 99.95), but positive predictive value was 55% (95% CI 40 to 69) overall and 29% (95% CI 13 to 49) when cabotegravir had been administered less than six months earlier. Some false-positive RNA results led to delay or discontinuation of injections. A specificity of 99.92% sounds decisive and produces a coin-flip positive predictive value here, because the prevalence being screened for is very low. That arithmetic is the audit.
Written into the record, not signed off as a reviewed claim
The comparison is partly pharmacology and partly whether the comparator was taken
In plain words
In the trial in women, injections were given 93% of the time they were due. In the same trial, fewer than half the blood samples from the tablet group had drug levels consistent with taking it daily. So a hazard ratio of 0.12 compares a drug that was delivered with a drug that partly was not.
What was measured
That the superiority of cabotegravir over daily oral prophylaxis reflects greater intrinsic antiviral protection rather than the difference between an administered drug and a self-taken one
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
HPTN 084 reported injection coverage of 93% of total person-years, and in a random subset of 405 participants in the oral arm, 812 of 1,929 plasma samples (42.1%) had tenofovir concentrations consistent with daily use. A separate nested case-control analysis of HPTN 083 established the concentration-response relationship on the cabotegravir side: minimum plasma cabotegravir at or above four times the protein-adjusted 90% inhibitory concentration was reached in 26% of participants who acquired HIV against 76% of matched controls, and was associated with a 93% reduction in acquisition risk relative to concentrations below one times that threshold (95% CI 76% to 98%, p<0.001). Two readings follow, and both are legitimate. Pharmacologically, the trials compare an assured exposure with a variable one rather than one molecule with another. Clinically, that is exactly the comparison a person choosing between them faces, and a drug that gets into the body is better than one that does not. The inference to resist is the third one: that cabotegravir is intrinsically more potent at preventing HIV than tenofovir-emtricitabine, which neither trial measured.
Written into the record, not signed off as a reviewed claim
Better bone than the comparator, measured on the surrogate rather than on fractures
In plain words
Bone density was measured in the prevention trial over two years, and the injection group did better than the tenofovir tablet group. As everywhere else in this class, what was measured is a scan result, not a broken bone.
What was measured
Change in bone mineral density over 105 weeks, cabotegravir against tenofovir disoproxil-emtricitabine
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
A prespecified bone substudy of HPTN 083 reported that long-acting cabotegravir had a better bone safety profile than tenofovir disoproxil-emtricitabine over 105 weeks, and the authors conclude that for individuals with low bone mineral density or other fracture risk factors, cabotegravir prevention should be considered over tenofovir-based prevention. The endpoint is bone mineral density, which is a surrogate. No prevention trial in this field has been powered for fracture, and this one was not either. The finding is a genuine measured difference and it belongs in a decision for someone with established osteoporosis; it is not evidence that fewer bones break.
Written into the record, not signed off as a reviewed claim
In treatment, failure is rare and disproportionately carries resistance
In plain words
Used for treatment with rilpivirine, monthly injections failed as rarely as daily tablets, seven people in each arm out of 591. But six of the seven injection failures had developed resistance mutations against three of the seven on tablets.
What was measured
That the excess of resistance among long-acting treatment failures is caused by the slow decline of drug from the intramuscular depot rather than by chance in 14 events
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
The pooled week 48 analysis of ATLAS (NCT02951052) and FLAIR (NCT02938520) covered 591 participants per arm, randomised to continue current oral therapy or switch to monthly intramuscular cabotegravir with rilpivirine after a four-week oral lead-in. Non-inferiority was met at a 4% margin for the primary and key secondary efficacy endpoints. Confirmed virological failure, two consecutive measurements at or above 200 copies per millilitre, occurred in 7 participants in each arm; resistance-associated mutations were present in 6 of 7 long-acting failures against 3 of 7 on oral therapy. Injection site reactions affected 83% of long-acting recipients and led to withdrawal of 6 (1%). The count is measured. That the difference is caused by the depot tail rather than by chance in 14 total events is an inference, mechanistically coherent and resting on small numbers, and it is the same inference the prevention data support from the other direction.
This order is fixed in code and does not count clicks or time on the page.
What is not here
7 questions this page could not answer
These sections were prepared and left out because there was nothing to put in them. They are listed rather than hidden, so the gaps in this record are visible.
What was measured, goal by goal — found nothing in the sources checked.
How close this is to real life — found nothing in the sources checked.
Felt, measured, or meaningful — found nothing in the sources checked.
How long anything takes — found nothing in the sources checked.
What it may clash with — found nothing in the sources checked.
Other ways to the same goal — found nothing in the sources checked.
What changed on this page — found nothing in the sources checked.
The record as stored
The full record, for auditing
Everything above is built from what is below. This layer keeps the technical vocabulary, record identifiers and every stored row, so a reader who wants to check the page can.
The older medicine-wide conclusion held in this record
Written for a clinical reader, and about the medicine as a whole rather than about one indication, population and set of trials. RNAWiki does not treat it as a programme conclusion and no reviewer has signed it off in that form. It is here word for word because it is what the record holds.
An integrase strand-transfer inhibitor formulated as a long-acting intramuscular suspension; it cut HIV acquisition by 66% against daily oral tenofovir-emtricitabine in 4,566 men who have sex with men and transgender women (hazard ratio 0.34) and by 88% in 3,224 women in sub-Saharan Africa (hazard ratio 0.12), and both trials stopped early for efficacy — while producing integrase resistance and delayed diagnosis in the breakthrough infections that did occur.
Recorded evidence blocks (9)
Q1
On the Cabotegravir label: indicated for what?
"APRETUDE is indicated for pre‑exposure prophylaxis (PrEP) to reduce the risk of sexually acquired HIV-1 infection in adults and adolescents weighing at least 35 kg who are at risk for HIV-1 acquisition. Individuals must have a negative HIV-1 test prior to initiating APRETUDE (with or without an oral lead-in with oral…": indications and usage on Cabotegravir's label. DailyMed label · 4338428e-43d4-4e02-ac9d-bd98e738a7da · 2025-04-11
Q2
53 registered trials of Cabotegravir — at which phases?
"This protocol was early terminated on 10/15/2024 due to low enrollment"; 1 of 53 registered studies
Show the evidence
TrialNCT05755204
terminated; "This protocol was early terminated on 10/15/2024 due to low enrollment"
recorded 2026-09-01 · last checked 2026-09-04
Q4
Human studies of Cabotegravir used GSK1265744 10 mg oral solution — over how long?
Human studies of Cabotegravir used "GSK1265744 10 mg oral solution". ClinicalTrials.gov · 2026-09-01
20 recorded entries; human; oral, tablet, intramuscular, subcutaneous; also "GSK1265744 5 mg tablet", "GSK1265744 30mg", "GSK1265744 5mg"
Show the evidence
human
NCT00812318
oral; GSK1265744 10 mg oral solution
NCT00812318
tablet; GSK1265744 5 mg tablet
NCT00920426
GSK1265744 30mg
NCT00920426
GSK1265744 5mg
NCT01593046
intramuscular; GSK1265744 LAP 800mg intramuscular injection
NCT01593046
subcutaneous; GSK1265744 LAP 200mg subcutaneous injection
14 more recorded rows
humanNCT01593046
intramuscular; GSK1265744 LAP 200mg intramuscular injection
humanNCT01593046
intramuscular; GSK1265744 LAP 400mg intramuscular injection
humanNCT01641809
GSK1265744 10 mg
humanNCT01641809
GSK1265744 30 mg
humanNCT01641809
GSK1265744 60 mg
humanNCT01754116
oral; GSK1265744 30 mg oral
humanNCT01754116
oral; Midazolam 3 mg oral + GSK1265744 30mg oral
humanNCT01754116
GSK1265744 400 mg (200 nm)
humanNCT01754116
GSK1265744 400 mg (1 micro m)
humanNCT01754116
GSK1265744 400 mg (5 micro m)
humanNCT01848340
150 mg GSK1265744B
humanNCT02799264
Cabotegravir 30 mg
humanNCT04484337
Cabotegravir 400 mg/mL
humanNCT04484337
Cabotegravir 200 mg/mL
recorded 2026-09-01 · last checked 2026-09-04
Q5
Cabotegravir's half-life is 1 week — which schedules were studied?
1 week, the half-life Cabotegravir's label states: "Concentrations were measured at steady-state 1 week after intramuscular administration of cabotegravir extended-release injectable suspensions given monthly or every 2 months. c Elimination half-life driven by slow absorption rate from the intramuscular injection site. d Dosing in mass balance studies: single-dose…" DailyMed label · 4338428e-43d4-4e02-ac9d-bd98e738a7da · 2025-04-11
Show the evidence
half lifepharmacokinetics
1 week; Concentrations were measured at steady-state 1 week after intramuscular administration of cabotegravir extended-release injectable suspensions given monthly or every 2 months. c Elimination half-life driven by slow absorption rate from the intramuscular injection site. d Dosing in mass balance studies: single-dose oral administration of [ 14 C] cabotegravir.
metabolismpharmacokinetics
Absorption a T max (days), median 7 Distribution % Bound to human plasma proteins >99.8 Blood-to-plasma ratio 0.52 CSF-to-plasma concentration ratio (median [range]) b 0.003 (0.002 to 0.004) Elimination t 1/2 (weeks), mean c 5.6 to 11.5 Metabolism Metabolic pathways UGT1A1 UGT1A9 (minor) Excretion Major route of elimination Metabolism % of dose excreted as total 14 C (unchanged drug) in urine d…
recorded 2025-04-11 · last checked 2026-09-04
Q6
Which 13 trials of Cabotegravir posted no result?
Posted no result
13 of 13 completed trials
Registrations
NCT00812318, NCT00659191, NCT00920296, NCT01467531, NCT01848340 and NCT01593046, and 7 more
Completion dates
oldest 2008-08; newest 2024-05-23
Show the evidence
Trial
NCT00812318
2008-08
NCT00659191
2008-11
NCT00920296
2009-09
NCT01467531
2012-02
NCT01848340
2013-07
NCT01593046
2013-11
7 further recorded trials
NCT01754116
2014-04
NCT02027454
2014-06
NCT02159131
2014-12
NCT02799264
2016-08
NCT02354950
2016-09-16
NCT02354937
2016-11-01
NCT05112939
2024-05-23
Q7
At the median, Cabotegravir's trials enrolled 132 people — anything larger?
Median enrolment
132
Largest enrolment
4570
Registered trials counted
52
Q8
What do 421 spontaneous reports say about Cabotegravir — 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.
Cabotegravir appears in spontaneous reports to regulators. Across the 10 most-reported reaction terms, 421 reaction mentions were counted: product use in unapproved therapeutic environment 68; viral load increased 66; product dose omission issue 64; virologic failure 52. FAERS via Open Targets · CHEMBL2403238 · 2026-06-24
Show the evidence
product use in unapproved therapeutic environment
68
viral load increased
66
product dose omission issue
64
virologic failure
52
injection site pain
50
pathogen resistance
48
4 more recorded rows
blood hiv rna increased
25
product complaint
19
product administered at inappropriate site
16
viral mutation identified
13
recorded 2026-06-24 · last checked 2026-09-04
Q9
Which 10 reactions does Cabotegravir's label not list?
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
✗ required summary fields resolved: 4 required field(s) not terminal: Why people use it, Best-supported result, Biggest unanswered question, Human evidence
✓ public claims reviewed: 0 reviewed claim(s); drafts are never rendered
✓ source coverage passed: 6 source rows
✓ no critical contamination: no quarantine open
✓ canonical metadata passed: slug and display name present
✓ no raw internal fields: enforced by the copy-contract test over the rendered page
This is a record of evidence. It is not medical advice, and it does not say this substance suits you. Nothing here says any substance on RNAWiki is appropriate for a child.