This page shows what was measured, who it was measured in, and what that does not settle.
What Efavirenz does in the body
HIV treatment as part of a combination.
Reverse transcriptase has to open and close like a hand to copy genetic material. Efavirenz does not go into the part of the enzyme that does the chemistry. It slots into a greasy pocket just beside it and holds the whole structure rigid, so the hand can no longer close. The enzyme is intact, present, and useless. Because the pocket is not doing anything essential for the virus otherwise, a single change to one amino acid in it can make the drug stop working entirely.
What happened in people
It suppressed HIV better than older treatment, and two thirds of the registered dose later worked as well with fewer side effects.
✓ Reviewed first-read answer
Where this came from
A person wrote this and a reviewer approved it against this exact record. It carries no effect size.
A reviewer approved this against this record. The reviewed-claim record carrying the exact population and effect size does not exist yet.
No source is stored against this line.
The limit that matters most
Strong study and ordinary-care evidence disagree on whether it doubles suicidal thoughts or acts.
Where it acts
HIV-1 reverse transcriptase in the cytoplasm of infected CD4-positive T cells; the side effects are generated in the central nervous system
Kind of result
The kind of result is not recorded
Supervision
Professional supervision is normally required. A regulator classifies this substance in a way that restricts how it is supplied.
What the registries record it as
The substance registry classes this as chemical.
FDA substance registry · JE6H2O27P8 · read 2026-08-29
Its recorded molecular formula is C14H9ClF3NO2.
US prescribing information · 13ca3456-e5bf-4bb1-af95-b1378658a358 · 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.
The limit a reviewer approved as the one that matters most here.
The four opening statements run to 116 words.
Words this page uses
Four words worth knowing first
Chosen from what this page shows, with each one explained before the word it depends on.
Comparator
A comparator is whatever the treatment was measured against.
A picture of it, and where the picture fails
It is like the other runner in a race.
Where that stops being true. A race has one winner. A study can show both arms improved.
What people get wrong. Results are read without asking what the other group got. Beating nothing is not beating a treatment.
The control condition against which the experimental intervention is assessed.
Randomisation
Randomisation means chance decides who gets which treatment.
A picture of it, and where the picture fails
It is like a coin toss deciding the groups.
Where that stops being true. A coin toss is fair once. Fairness here comes from doing it for everyone.
What people get wrong. It is thought to make groups identical. It makes them similar on average, including on things nobody measured.
Allocation of participants to arms by a chance process, so that unmeasured factors are balanced in expectation.
Absolute difference
An absolute difference is how many more people in a hundred were affected.
A picture of it, and where the picture fails
It is like counting heads in two rooms of a hundred.
Where that stops being true. Heads are easy to count. Study results carry a margin of error too.
What people get wrong. It is confused with a percentage change, which can look far larger.
The arithmetic difference in event rates between arms.
Confidence interval
A confidence interval is the range the true answer is likely to sit in.
A picture of it, and where the picture fails
It is like a weather forecast giving a range rather than one number.
Where that stops being true. A forecast range covers tomorrow. This one covers what the study could resolve.
What people get wrong. The middle number is read as the answer. A range crossing zero means no change is still possible.
An interval estimate that would contain the true parameter in a stated proportion of repeated studies.
What happened in people◇Read from sources, not yet reviewed
What happened in people
Each card is one study: the exact question it asked, who was in it, and whether it showed what it set out to show.
Proportion with plasma HIV-1 RNA suppressed to undetectable levels against indinavir-based therapy
✓ The study showed what it set out to show
Who was studied
Study 006 (DMP 266-006)
How many people
450
Study design
Phase 3, randomised, open-label, three arms
Compared against
Not recorded for this study
Kind of result
A number that stands in for health
What was found
70% versus 48%, p<0.001
Repeated elsewhere
Replicated
What this does not prove. Meeting one endpoint in one population does not carry to other goals or other people.
The limits of this study, and where it came from
Main limit. No limitation is recorded for this study.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Oral capsule and film-coated tablet, single agent and in fixed-dose combinations
Interval reported. Not recorded in this summary
Written into the record, not signed off as a reviewed claim.
Difference in the proportion with viral load below 200 copies per millilitre at week 48, efavirenz 400 mg against 600 mg
✓ The study showed what it set out to show
Who was studied
ENCORE1 (NCT01011413)
How many people
630
Study design
Randomised, double-blind, placebo-controlled, non-inferiority, 48-week primary with 96-week follow-up
Compared against
A dummy treatment
Kind of result
A number that stands in for health
What was found
94.1% versus 92.2%, difference 1.85% (95% CI -2.1 to 5.79); at week 96, 90.0% versus 90.6% (95% CI -5.2 to 4.0, p=0.72)
Repeated elsewhere
Replicated
What this does not prove. Meeting one endpoint in one population does not carry to other goals or other people.
The limits of this study, and where it came from
Main limit. The reduced dose produced significantly fewer drug-related adverse events and fewer discontinuations for them, and higher CD4 counts. The trial was funded by a foundation and a university, sixteen years after the higher dose was registered.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Oral capsule and film-coated tablet, single agent and in fixed-dose combinations
Interval reported. 95% CI -2
Written into the record, not signed off as a reviewed claim.
Time to suicidality, defined as suicidal ideation or attempted or completed suicide, efavirenz-containing against efavirenz-free regimens
✗ The study did not show it
Who was studied
Pooled ACTG suicidality analysis (NCT00013520, NCT00050895, NCT00084136, NCT00118898)
How many people
5332
Study design
Participant-level pooled analysis of four randomised treatment-naive trials
Compared against
Not recorded for this study
Kind of result
A number that stands in for health
What was found
Hazard ratio 2.28 (95% CI 1.27 to 4.10, p=0.006); attempted or completed suicide hazard ratio 2.58 (95% CI 0.94 to 7.06, p=0.065)
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. Eight suicides in the efavirenz group against one. There was no standardised suicidality questionnaire, and efavirenz was open-label in three of the four contributing studies. A routine-care cohort using marginal structural models later found a weighted hazard ratio of 1.21 (95% CI 0.66 to 2.28).
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Oral capsule and film-coated tablet, single agent and in fixed-dose combinations
Interval reported. 95% CI 1
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
Efavirenz
What a person takes: Oral capsule and film-coated tablet, single agent and in fixed-dose combinations.
The measurement behind this step
Taken once daily on an empty stomach, conventionally at bedtime so that the central nervous system effects occur during sleep. A high-fat meal raises exposure enough to matter. Efavirenz both induces and is metabolised by cytochrome P450 enzymes, principally CYP2B6 with a CYP3A4 contribution, which makes its interaction list long and includes rifampicin, methadone, hormonal contraceptives and several antifungals.
Getting in
Swallowed once a day, and it is why once a day became possible
One tablet, once daily, taken on an empty stomach and usually at bedtime so the dizziness happens while asleep. The regimen it replaced needed dosing every eight hours around meals.
╌╌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
Terminal half-life is 40 to 55 hours after multiple dosing, which is what supports once-daily administration and also what makes the drug the last one to disappear when a regimen is stopped, leaving a period of effective monotherapy in which resistance can be selected. A high-fat meal raises exposure enough that the label specifies dosing on an empty stomach. Efavirenz induces its own metabolism through CYP3A4 and is cleared principally by CYP2B6.
The molecule is small and greasy, so it moves into cells without help. It also crosses into the central nervous system, which is where the vivid dreams, dizziness and mood changes come from.
──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
Efavirenz is highly lipophilic and over 99% protein-bound, and it distributes into the central nervous system, where its concentration correlates with neuropsychiatric symptom frequency. Plasma exposure varies roughly three-fold by CYP2B6 516 genotype, so the same milligram dose is a different pharmacological dose in different people, and the slow-metaboliser genotype is markedly more common in populations of African ancestry.
It wedges into a pocket that only exists once it arrives
Beside the working part of the copying enzyme there is a greasy gap that opens only when a drug like this pushes into it. Efavirenz forces it open and stays there.
╌╌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 non-nucleoside binding pocket in the p66 subunit is not present in the unliganded enzyme; it is created by rotation of tyrosine 181 and tyrosine 188 out of the way as the drug binds. The site sits about 10 angstroms from the polymerase catalytic triad, so inhibition is allosteric and non-competitive with respect to the nucleotide substrate.
Copying DNA requires the enzyme to move through a repeating cycle of shapes. With the drug wedged in place the structure is rigid. The enzyme is still there and still holding the genetic material; it simply cannot complete a step.
╌╌Described, with no measurement named. No measurement is named for this step, so it is drawn as an unconfirmed link.
The measurement behind this step
Binding restricts mobility of the thumb subdomain and the primer grip, so the enzyme cannot execute the conformational change that follows nucleotide binding. Catalysis is blocked rather than the substrate being displaced. Because the pocket has no catalytic role, K103N and Y181C abolish binding while leaving polymerase function intact, which is why a single substitution confers high-level resistance across the entire first-generation class.
Virus falls fast, and stays down until one mutation arrives
Viral load drops and stays down, in nine out of ten patients at two years in the trials. What ends it is not gradual loss of effect but a single mutation, which then also removes every other drug in the same family.
╌╌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
Week 96 suppression below 50 copies per millilitre was 89% in ACTG 5142 and 90% at either dose in ENCORE1. Failure is typically abrupt and accompanied by K103N, which confers high-level cross-resistance to efavirenz and nevirapine at no measurable fitness cost, so the mutation persists in the reservoir and in transmitted virus. Pretreatment non-nucleoside resistance reached an estimated 11.0% in southern Africa by 2016, which is the reason the global first line moved to dolutegravir.
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.
Fewer people every year. It has been superseded as first-line therapy in the WHO and United States guidelines by dolutegravir, and now serves mainly as an alternative agent and in regimens where a specific interaction rules out an integrase inhibitor.
Who is missing from the studies
Which groups were under-represented in the studies has not been recorded for this substance. Pregnancy, breastfeeding, children, older adults, and people with liver or kidney conditions are commonly excluded from trials; nothing here says whether they were.
What the label states about particular groups
On pediatric, the label states: “The safety, pharmacokinetic profile, and virologic and immunologic responses of efavirenz were evaluated in antiretroviral-naive and -experienced HIV-1 infected pediatric patients 3 months to 21 years of age in three open-label clinical trials [see Adverse Reactions ( 6.2 ),Clinical Pharmacology ( 12.3 ), and Clinical Studies ( 14.2 )].”
US prescribing information · 13ca3456-e5bf-4bb1-af95-b1378658a358 · read 2026-08-30
On older people, the label states: “Clinical studies of efavirenz did not include sufficient numbers of subjects aged 65 years and over to determine whether they respond differently from younger subjects.”
US prescribing information · 13ca3456-e5bf-4bb1-af95-b1378658a358 · read 2026-08-30
On people who are pregnant, the label states: “Animal Data Effects of efavirenz on embryo-fetal development have been studied in three nonclinical species (cynomolgus monkeys, rats, and rabbits).”
US prescribing information · 13ca3456-e5bf-4bb1-af95-b1378658a358 · read 2026-08-30
On people who are breastfeeding, the label states: “Risk Summary The Centers for Disease Control and Prevention recommend that HIV-infected mothers not breastfeed their infants to avoid risking postnatal transmission of HIV.”
US prescribing information · 13ca3456-e5bf-4bb1-af95-b1378658a358 · read 2026-08-30
On people with reduced liver function, the label states: “Efavirenz is not recommended for patients with moderate or severe hepatic impairment because there are insufficient data to determine whether dose adjustment is necessary.”
US prescribing information · 13ca3456-e5bf-4bb1-af95-b1378658a358 · read 2026-08-30
Where the result stopped carrying
The pregnancy contraindication restricted access for women of childbearing potential for roughly a decade on preclinical primate data, and was reversed in the 2013 WHO guidelines
The single-mutation resistance barrier drove pretreatment non-nucleoside resistance to an estimated 11.0% in southern Africa by 2016, above the WHO 10% threshold for changing national first-line therapy
This is a scope explorer, not a diagnosis engine.
It shows who was studied so you can see whether people similar to you were included.
RNAWiki cannot tell whether a study fits you. It can show who was in it.
What it would be like to take◇Read from sources, not yet reviewed
Why it might seem to do nothing
A real effect and a noticed effect are different things. These are the recorded reasons the two come apart.
It was studied in different people
The people in the studies were not much like the reader.
On this record: Which groups were under-represented in the studies has not been recorded for this substance. Pregnancy, breastfeeding, children, older adults, and people with liver or kidney conditions are commonly excluded from trials; nothing here says whether they were.
The evidence may simply be wrong
Small early studies often do not hold up.
On this record: RNAWiki has not yet published a reviewed conclusion for this use.
Other reasons RNAWiki checked and found nothing for (11)
It was studied for a different goal
The studies measured something else entirely. Nothing in this record points to this reason.
A different form was studied
The studied form is not the form on the shelf. Nothing in this record points to this reason.
There was nothing to correct
Where a level is already normal, topping it up may change nothing. Nothing in this record points to this reason.
Something else had to happen too
In the studies it was paired with training, a diet or another treatment. Nothing in this record points to this reason.
The change is too small to feel
A real change can still sit below what a person notices. Nothing in this record points to this reason.
Day-to-day swing hides it
Sleep, food, stress and time of day move most numbers more than this would. Nothing in this record points to this reason.
Not enough time yet
The studies ran longer than the person has waited. Nothing in this record points to this reason.
It was not taken as studied
Missed days change the result, and studies count them. Nothing in this record points to this reason.
Something else changed at the same time
Two changes at once cannot be told apart afterwards. Nothing in this record points to this reason.
The product may not be what it says
Contents of a sold product are not always what the label states. Nothing in this record points to this reason.
No recorded reason
RNAWiki has nothing stored that would explain it. Nothing in this record points to this reason.
None of these is a reason to take more. Taking more is not a step this page ever suggests.
What it would be like to take◇Read from sources, not yet reviewed
What taking it involves
The recorded facts about getting hold of it and using it. Nothing here is a suggestion about what you should do.
How it is supplied
Prescription only
❝ Quoted from a source
Where this came from
Copied from a source RNAWiki stored, with the source named.
Read from the recorded approval status.
No source is stored against this line.
Form and route
Oral capsule and film-coated tablet, single agent and in fixed-dose combinations
✎ 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
Professional supervision is normally required. A regulator classifies this substance in a way that restricts how it is supplied.
❝ Quoted from a source
Where this came from
Copied from a source RNAWiki stored, with the source named.
Suppression classes recorded: S3.
No source is stored against this line.
What is in the pack
Taken once daily on an empty stomach, conventionally at bedtime so that the central nervous system effects occur during sleep. A high-fat meal raises exposure enough to matter.
✎ 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: Efavirenz both induces and is metabolised by cytochrome P450 enzymes, principally CYP2B6 with a CYP3A4 contribution, which makes its interaction list long and includes rifampicin, methadone, hormonal contraceptives and several antifungals.
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
Central nervous system effects occur in more than half of patients in the first weeks: dizziness, abnormal dreams, impaired concentration, insomnia. Most attenuate but not all do. Psychiatric symptoms including severe depression are labelled, and the randomised suicidality signal is described in the audits above. Rash occurs commonly and is usually mild. Hepatotoxicity, hyperlipidaemia and gynaecomastia are labelled. The pregnancy contraindication that once accompanied this drug has been removed following human birth-outcome data, and the WHO recommends it throughout pregnancy including the first trimester.
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 capsule and film-coated tablet, single agent and in fixed-dose combinations
✎ 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 high-fat meal raises exposure enough to matter.
✎ 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. The rest of the recorded wording: Efavirenz both induces and is metabolised by cytochrome P450 enzymes, principally CYP2B6 with a CYP3A4 contribution, which makes its interaction list long and includes rifampicin, methadone, hormonal contraceptives and several antifungals.
No source is stored against this line.
What is recorded as being sold
42 products list this as an active ingredient in the United States drug directory. 30 of them contain it and nothing else.
FDA National Drug Code directory · 48087-0062 · read 2026-08-29
They are sold as capsule, powder, tablet and tablet, film coated, taken oral.
FDA National Drug Code directory · 48087-0062 · read 2026-08-29
The regulator's established pharmacologic class for it is cytochrome p450 2b6 inducers [moa], cytochrome p450 2c19 inhibitors [moa] and cytochrome p450 2c9 inhibitors [moa].
FDA National Drug Code directory · 48087-0062 · read 2026-08-29
16 published labels name it as an active ingredient. 6 of them describe this substance alone, which is where its own label text on this page comes from.
US prescribing information · 5f261872-d705-4549-a43d-2ad6b0164dc3 · read 2026-08-29
Those labels are classed as human prescription drug.
US prescribing information · 5f261872-d705-4549-a43d-2ad6b0164dc3 · read 2026-08-29
Efavirenz is oral at 3 DOSAGE FORMS & STRENGTHS • Efavirenz Tablets, USP 600 mg 600-mg tablets are yellow, biconvex, capsule-shaped, film-coated tablets, engraved with "ML 12" on one side and plain on the other side. •Tablets: 600 mg ( 3 ), recorded as fda label in effect 2024-06-28 in the United States.
US prescribing information · 13ca3456-e5bf-4bb1-af95-b1378658a358 · read 2026-08-30
Recorded price in US: 1.34911 USD per one unit as the pricing file counts it — a tablet, capsule, patch or single item, across 4 priced products whose strengths and pack forms differ, as of 2026-08-26, paid by retail pharmacies buying the product, as surveyed by the Centers for Medicare & Medicaid Services. It is not a list price, an insurance price, or what anyone pays at a counter..
Recorded source · 2026-08-26 · read 2026-08-28
Evidence carries across two names for one substance. It does not carry across a salt, a mirror form or a mixture.
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.
Self-experiment planning is not offered for a prescription or clinician-supervised medicine. The questions below are for a clinician or pharmacist.
Questions worth asking
Which of the trials of Efavirenz 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 central nervous system defects in three of twenty cynomolgus monkey fetuses predicted human teratogenicity — 2,026 first-trimester human exposures produced one neural tube defect
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 two-fold suicidality hazard measured in randomised trial populations transfers unchanged to routine care, where a cohort analysis found a weighted hazard ratio of 1.21
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 dose carried from phase 2 into registration was the dose the drug required, which held as an assumption for sixteen years and was wrong by a third
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 Efavirenz 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.
Study 006: 70% suppressed against 48% on the protease inhibitor standard
In plain words
The trial that established the drug put it against indinavir, then the best available. Efavirenz with two nucleosides suppressed 70% of patients to undetectable against 48%, and drove far fewer people off treatment with side effects.
What was measured
Proportion with plasma HIV-1 RNA suppressed to undetectable, and discontinuation for adverse events
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
Study 006 (DMP 266-006) randomised 450 patients naive to lamivudine, non-nucleosides and protease inhibitors, open-label, to efavirenz 600 mg with zidovudine and lamivudine, to indinavir 800 mg every eight hours with zidovudine and lamivudine, or to efavirenz plus indinavir. Plasma HIV-1 RNA was suppressed to undetectable in 70% of the efavirenz-nucleoside group against 48% of the indinavir-nucleoside group (p<0.001); the efavirenz-plus-indinavir arm reached 53%. CD4 counts rose by 180 to 201 cells per cubic millimetre across all three arms. Discontinuation for adverse events was 27% on efavirenz against 43% on indinavir (p=0.005). The dosing schedule is the part of this result that changed practice: once daily against every eight hours.
Written into the record, not signed off as a reviewed claim
ACTG 5142: 89% against 77% on lopinavir-ritonavir at 96 weeks
In plain words
A publicly funded trial in 757 patients compared efavirenz with a boosted protease inhibitor and with a regimen containing neither nucleoside. Efavirenz won on virological failure, and the nucleoside-sparing arm produced more resistance.
What was measured
Time to virological failure and proportion below 50 copies per millilitre at week 96
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
ACTG 5142 (NCT00050895) randomised 757 treatment-naive patients with a median CD4 count of 191 cells per cubic millimetre to efavirenz with two nucleoside reverse transcriptase inhibitors, to lopinavir-ritonavir with two nucleosides, or to lopinavir-ritonavir with efavirenz and no nucleosides. At a median follow-up of 112 weeks, time to virological failure was longer in the efavirenz group than in the lopinavir-ritonavir group (p=0.006). At week 96, 89% of the efavirenz group, 77% of the lopinavir-ritonavir group and 83% of the nucleoside-sparing group had fewer than 50 copies per millilitre (p=0.003 for efavirenz against lopinavir-ritonavir). Time to discontinuation for toxicity did not differ between groups, and resistance mutations at virological failure were more frequent in the nucleoside-sparing group.
Written into the record, not signed off as a reviewed claim
The registered dose was a third too high, and an academic trial proved it in 2014
In plain words
Efavirenz was approved at 600 mg a day in 1998 and stayed there for sixteen years. A trial funded by a foundation, not a manufacturer, then randomised 630 patients to 400 mg or 600 mg. The lower dose was non-inferior, produced higher CD4 counts, and caused significantly fewer drug-related side effects.
What was measured
That the dose selected in phase 2 dose-ranging and carried into registration was the dose the drug needed — an assumption that held for sixteen years and was wrong by a third
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
ENCORE1 (NCT01011413) was a double-blind, placebo-controlled non-inferiority trial at 38 sites in 13 countries in treatment-naive adults, all on tenofovir and emtricitabine. At week 48, 94.1% of the 400 mg group against 92.2% of the 600 mg group had viral load below 200 copies per millilitre, difference 1.85% (95% CI -2.1 to 5.79) against a -10% margin. CD4 counts were higher on the lower dose by 25 cells per microlitre (95% CI 6 to 44, p=0.01). Study-drug-related adverse events occurred in 118 against 146 patients, difference -10.5% (95% CI -18.2 to -2.8, p=0.01), and 6 (2%) against 18 (6%) stopped treatment because of them (p=0.01). At week 96 suppression was 90.0% against 90.6%, difference -0.6 (95% CI -5.2 to 4.0, p=0.72). The trial was funded by the Bill and Melinda Gates Foundation and UNSW Australia. The finding was not a refinement of a marginal dose. It was one third of the active ingredient in every efavirenz tablet on earth, removable at no measured cost in efficacy, sitting undiscovered for sixteen years because nobody whose product it was had a reason to look.
Written into the record, not signed off as a reviewed claim
Contraindicated in early pregnancy on three monkeys, cleared by 2,026 human pregnancies
In plain words
Efavirenz was labelled as dangerous in the first trimester because three of twenty monkey fetuses had brain and spinal defects. Human data eventually accumulated: 2,026 first-trimester exposures produced one neural tube defect, a rate no different from the general population, and the WHO reversed its guidance in 2013.
What was measured
That central nervous system malformations in three of twenty cynomolgus monkey fetuses predicted human teratogenicity — an inference that shaped guidelines for a decade and that 2,026 human pregnancies did not support
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
The original signal was preclinical: central nervous system malformations in cynomolgus monkey fetuses exposed in the first trimester, which put efavirenz into the old FDA pregnancy category D and produced guidance against its use in women who might conceive. Ford and colleagues pooled human birth outcomes three times as data accumulated. By 2014 the review covered 23 studies, of which 21 reported outcomes on 2,026 live births after first-trimester efavirenz exposure. Forty-four congenital anomalies were reported, a pooled proportion of 1.63% (95% CI 0.78 to 2.48), of which exactly one was a neural tube defect, an incidence of 0.05% (95% CI below 0.01 to 0.28) and comparable to the general population. Across twelve studies with a comparator, the relative risk of any congenital anomaly against non-efavirenz regimens was 0.78 (95% CI 0.56 to 1.08). This review fed directly into the 2013 WHO antiretroviral guidelines, which recommended efavirenz for adults regardless of sex and throughout pregnancy including the first trimester. The reversal cost years of restricted access for women in exactly the countries where the drug was the only realistic option.
Written into the record, not signed off as a reviewed claim
Suicidality: a two-fold hazard in trials, no clear signal in routine care
In plain words
Pooling four randomised trials found suicidal thoughts and acts roughly twice as common on efavirenz, with eight suicides against one. A cohort study in ordinary clinical care found no clear increase. Both analyses are competent, and the disagreement has not been resolved.
What was measured
That the two-fold suicidality hazard measured in trial populations describes the risk faced by patients in routine care, or that its absence in cohort studies refutes the randomised finding
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
Mollan and colleagues analysed participant-level data from four AIDS Clinical Trials Group treatment-naive studies conducted 2001 to 2010 (NCT00013520, NCT00050895, NCT00084136, NCT00118898), 3,241 randomised to efavirenz-containing and 2,091 to efavirenz-free regimens, median follow-up 96 weeks. Suicidality incidence per 1,000 person-years was 8.08 (47 events) against 3.66 (15 events), hazard ratio 2.28 (95% CI 1.27 to 4.10, p=0.006). Attempted or completed suicide was 2.90 against 1.22 per 1,000 person-years, hazard ratio 2.58 (95% CI 0.94 to 7.06, p=0.065), with 8 suicides against 1. The authors note there was no standardised suicidality questionnaire and that efavirenz was open-label in three of the four studies. A subsequent cohort of 597 adults initiating therapy in routine United States care, using marginal structural models to handle channelling bias, found a weighted hazard ratio of 1.21 (95% CI 0.66 to 2.28). A 2021 transportability analysis reweighted the trial effect onto a cohort of 8,291 routine-care patients and obtained a transported hazard ratio of 1.8 (95% CI 0.9 to 4.4) against 2.3 (1.2 to 4.4) in the trials, an attenuation of more than 20%. What is measured is the randomised hazard ratio. What is inferred, in either direction, is which of these two populations a given reader belongs to.
Written into the record, not signed off as a reviewed claim
One amino acid ends it, and by 2016 that had happened across a continent
In plain words
A single change at position 103 of reverse transcriptase makes efavirenz stop working, and it costs the virus nothing to carry. By 2016 roughly one in ten people starting treatment in southern and eastern Africa already had that kind of resistance before their first dose, which is the threshold at which the WHO says a country must change its first-line drug.
What was measured
Pooled prevalence of pretreatment non-nucleoside reverse transcriptase inhibitor resistance by region in 2016, and its yearly rate of increase
Effect estimate
No reviewed effect estimate exists for this record.
Limits
This entry records a failure.
From the source
A systematic review and meta-regression of 358 datasets covering 56,044 adults in 63 low-income and middle-income countries estimated 2016 pretreatment non-nucleoside resistance prevalence at 11.0% (95% CI 7.5 to 15.9) in southern Africa, 10.1% (5.1 to 19.4) in eastern Africa, 7.2% (2.9 to 16.5) in western and central Africa and 9.4% (6.6 to 13.2) in Latin America and the Caribbean. The yearly increase in the odds of pretreatment resistance was 23% (95% CI 16 to 29) in southern Africa and 11% to 17% elsewhere. The WHO threshold for changing national first-line therapy is 10%. The structural cause is that the non-nucleoside pocket is not catalytic, so K103N and Y181C abolish drug binding without the fitness penalty that constrains resistance to nucleoside analogues or to second-generation integrase inhibitors. The failure being audited here is not that patients failed. It is that a drug class with a one-mutation barrier was deployed as the global first line for fifteen years, and the resistance that ended it was predictable from the crystal structure.
Written into the record, not signed off as a reviewed claim
The side effects are a genotype, and the genotype is unevenly distributed
In plain words
How much efavirenz ends up in the blood depends on a common variant in the enzyme that clears it. People carrying two copies of the slow variant have roughly three times the drug exposure, and that variant is much more common in people of African ancestry, who are also the population the drug was most widely deployed in.
What was measured
Median efavirenz 24-hour area under the curve by CYP2B6 516 genotype: 44, 60 and 130 microgram-hours per millilitre
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
ACTG A5097s measured efavirenz plasma concentration-time profiles and central nervous system symptoms in 154 participants: 89 European-American, 50 African-American, 15 Hispanic. The CYP2B6 T/T genotype at position 516 was present in 20% of African-Americans against 3% of European-Americans and was associated with substantially greater exposure: median 24-hour area under the curve was 44, 60 and 130 microgram-hours per millilitre for G/G, G/T and T/T respectively (p<0.0001). The G516T genotype was associated with central nervous system symptoms at week 1 (p=0.036). No association was found for CYP3A4, CYP3A5 or MDR1 polymorphisms. The three-fold exposure difference across a common genotype is also the pharmacological setting for the ENCORE1 result: a fixed 600 mg dose is a very different dose in different people, and the population in which the standard dose was set was not the population in which most of it was eventually taken.
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What is not here
7 questions this page could not answer
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Felt, measured, or meaningful — found nothing in the sources checked.
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The record as stored
The full record, for auditing
Everything above is built from what is below. This layer keeps the technical vocabulary, record identifiers and every stored row, so a reader who wants to check the page can.
The older medicine-wide conclusion held in this record
Written for a clinical reader, and about the medicine as a whole rather than about one indication, population and set of trials. RNAWiki does not treat it as a programme conclusion and no reviewer has signed it off in that form. It is here word for word because it is what the record holds.
A non-nucleoside inhibitor that wedges into a pocket beside the active site of HIV reverse transcriptase and stops the enzyme flexing; it suppressed 70% of treatment-naive patients against 48% on the protease inhibitor standard of 1999 and 89% against 77% on lopinavir-ritonavir in 2008, and a later independent trial then showed that two thirds of the registered dose worked just as well with fewer side effects.
Recorded evidence blocks (11)
Q2
On the Efavirenz label: indicated for what?
"1 INDICATIONS & USAGE Efavirenz in combination with other antiretroviral agents is indicated for the treatment of human immunodeficiency virus type 1 (HIV-1) infection in adults and in pediatric patients at least 3 months old and weighing at least 3.5 kg. Efavirenz is a non-nucleoside reverse transcriptase inhibitor…": indications and usage on Efavirenz's label. DailyMed label · 13ca3456-e5bf-4bb1-af95-b1378658a358 · 2024-06-28
Q3
238 registered trials of Efavirenz — at which phases?
Registered studies posting no result
170 of 238
238 registered studies of Efavirenz: 56 phase2, 56 phase3, 53 phase1, 40 phase4, 32 na, 11 na or unstated, 1 early phase1. CLINICALTRIALS_SNAPSHOT · 2026-09-01
920 with a PubMed record
Show the evidence
phase2
56
phase3
56
phase1
53
phase4
40
na
32
na or unstated
11
9 more recorded rows
early phase1
1
completed
198
unknown
15
terminated
10
withdrawn
5
not yet recruiting
4
no longer available
2
recruiting
2
suspended
2
recorded 2026-09-01 · last checked 2026-09-04
Q4
11 of Efavirenz's trials stopped: futility/efficacy, accrual/recruitment, funding/business, other?
futility/efficacy (1), accrual/recruitment (4), funding/business (3) and other (3): Efavirenz's stop wording, clustered. CLINICALTRIALS_SNAPSHOT · 2026-09-01
"A delay in protocol approval and approval of laboratory sites in Salvador, Brazil left too little time for completion of enrollment into the study."; 11 of 238 registered studies
Show the evidence
Trial
NCT00523458
terminated; "A delay in protocol approval and approval of laboratory sites in Salvador, Brazil left too little time for completion of enrollment into the study."
NCT00533390
terminated; "Lack of financial support and low inclusion rate"
NCT00737724
terminated; "Other published trials showed definitive expected superiority of Group 1"
NCT00775606
terminated; "Study stopped 12/2010 due to poor enrollment. Only 15 of 60 needed enrolled."
NCT01194856
terminated; "Closed due to low enrollment"
NCT01254656
terminated; "See termination reason in detailed description."
5 further recorded trials
NCT01293123
terminated; "Did not meet enrollment goals"
NCT01515813
withdrawn; "On 05/08/12, team working on revising protocol and re-open study under version 2.0"
NCT01980342
terminated; "loss of funding"
NCT02631473
suspended; "Study is on hold whilst a grant application for further funding is put together"
NCT04504045
terminated; "Slow recruitment due to COVID-19, the study was stopped when recruited numbers fulfilled the pre-defined lower sample size."
recorded 2026-09-01 · last checked 2026-09-04
Q5
Human studies of Efavirenz used Efavirenz capsules 200 mg and 600 mg — over how long?
studies of Efavirenz used the recorded amount. ClinicalTrials.gov · 2026-09-01
18 recorded entries; human; also "Efavirenz capsules 200 mg and 600 mg", "Efavirenz 600mg", "Efavirenz(Sustiva)600 mg"
Efavirenz's half-life is 10 days — which schedules were studied?
10 days, the half-life Efavirenz's label states: "Multiple doses of 200-400 mg per day for 10 days resulted in a lower than predicted extent of accumulation (22-42% lower) and a shorter terminal half-life of 40-55 hours (single dose half-life 52-76 hours)." DailyMed label · 13ca3456-e5bf-4bb1-af95-b1378658a358 · 2024-06-28
tmax 3-5 hours.
Show the evidence
half lifepharmacokinetics
10 days; Multiple doses of 200-400 mg per day for 10 days resulted in a lower than predicted extent of accumulation (22-42% lower) and a shorter terminal half-life of 40-55 hours (single dose half-life 52-76 hours).
tmaxpharmacokinetics
3-5 hours; Time-to-peak plasma concentrations were approximately 3-5 hours and steady-state plasma concentrations were reached in 6-10 days.
metabolismpharmacokinetics
Metabolism Studies in humans and in vitro studies using human liver microsomes have demonstrated that efavirenz is principally metabolized by the cytochrome P450 system to hydroxylated metabolites with subsequent glucuronidation of these hydroxylated metabolites.
recorded 2024-06-28 · last checked 2026-09-04
Q7
Which running trial of Efavirenz could settle lifespan?
NCT07482085 measures Median survival time, reading out 2028-12.
1 open trial; n 246; "Efavirenz for the Treatment of Creutzfeldt-Jakob Disease"
Show the evidence
TrialNCT07482085
"Efavirenz for the Treatment of Creutzfeldt-Jakob Disease"; n 246; "Median survival time"; 2028-12
Q8
Which 104 trials of Efavirenz posted no result?
Posted no result
104 of 104 completed trials
Registrations
NCT00001086, NCT00000939, NCT00000912, NCT00000914, NCT00001087 and NCT00005018, and 98 more
Completion dates
oldest 1999-09; newest 2023-12-31
Show the evidence
Trial
NCT00001086
1999-09
NCT00000939
2000-01
NCT00000912
2000-05
NCT00000914
2000-06
NCT00001087
2000-07
NCT00005018
2000-10
14 further recorded trials
NCT00000903
2001-07
NCT00006190
2001-11
NCT00000918
2002-02
NCT00005918
2002-04
NCT00000919
2002-11
NCT00000893
2002-12
NCT00013897
2003-04
NCT00000885
2003-06
NCT00001758
2003-08
NCT00023413
2004-02
NCT00005762
2004-05
NCT00016601
2004-05
NCT00196599
2004-09
NCT00196612
2004-09
Q9
At the median, Efavirenz's trials enrolled 76 people — anything larger?
Median enrolment
76
Largest enrolment
29612
Registered trials counted
229
Q10
What do 3605 spontaneous reports say about Efavirenz — 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.
Efavirenz appears in spontaneous reports to regulators. Across the 10 most-reported reaction terms, 3605 reaction mentions were counted: virologic failure 714; drug resistance 532; viral mutation identified 454; pathogen resistance 353. FAERS via Open Targets · CHEMBL223228 · 2026-06-24
Show the evidence
virologic failure
714
drug resistance
532
viral mutation identified
454
pathogen resistance
353
drug interaction
315
depression
279
4 more recorded rows
treatment failure
262
abortion spontaneous
250
small for dates baby
239
immune reconstitution inflammatory syndrome
207
recorded 2026-06-24 · last checked 2026-09-04
Q11
Which 10 reactions does Efavirenz's label not list?
( 7 ) 7.1 Potential for efavirenz to Affect other Drugs Efavirenz has been shown in vivo to induce CYP3A and CYP2B6.
drug_interactions
Other compounds that are substrates of CYP3A or CYP2B6 may have decreased plasma concentrations when coadministered with efavirenz 7.2 Potential for Other Drugs to Affect efavirenz Drugs that induce CYP3A activity (e.g., phenobarbital, rifampin, rifabutin) would be expected to increase the clearance of efavirenz resulting in lowered plasma concentrations [see Dosage and Administration ( 2.2 )].
drug_interactions
Immunosuppressants: Cyclosporine, tacrolimus, sirolimus, and others metabolized by CYP3A ↓ immunosuppressant Dose adjustments of the immunosuppressant may be required.
pharmacokinetics
Metabolism Studies in humans and in vitro studies using human liver microsomes have demonstrated that efavirenz is principally metabolized by the cytochrome P450 system to hydroxylated metabolites with subsequent glucuronidation of these hydroxylated metabolites.
pharmacokinetics
The in vitro studies suggest that CYP3A and CYP2B6 are the major isozymes responsible for efavirenz metabolism.
pharmacokinetics
Drug Interaction Studies Efavirenz has been shown in vivo to cause hepatic enzyme induction, thus increasing the biotransformation of some drugs metabolized by CYP3A and CYP2B6.
2 more recorded rows
Interaction statementpharmacokinetics
In in vitro studies, efavirenz did not inhibit CYP2E1 and inhibited CYP2D6 and CYP1A2 (Ki values 82-160 μM) only at concentrations well above those achieved clinically.
Interaction statementpharmacokinetics
Coadministration of efavirenz with drugs primarily metabolized by CYP2C9, CYP2C19, CYP3A, or CYP2B6 isozymes may result in altered plasma concentrations of the coadministered drug.
ChEMBL 37 — CC BY-SA 3.0 Unported · ChEMBL ATC CC BY-SA · ClinicalTrials.gov — US Government work · Open Targets 26.06 — CC0 · mixed register set; per-register licences in docs/specs/corpus-20k-sources.md · openFDA / DailyMed — US Government work
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