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Module 19210 lessonsRxPrep 2023 HIV entry inhibitor material, reconciled with NIH Adult, Adolescent, Pediatric, and Perinatal HIV Guidelines and current FDA labeling through August 2026

HIV Entry and Attachment Inhibitors

Map HIV attachment and fusion to maraviroc, fostemsavir, ibalizumab, and enfuvirtide, then integrate tropism, multidrug resistance, delivery, interactions, toxicity, and accountable salvage-regimen design.

01

Trace attachment, coreceptor engagement, gp41 refolding, and membrane fusion in the HIV-1 entry sequence.

02

Differentiate host-directed and virus-directed entry inhibitors by molecular target.

03

Use coreceptor tropism testing to determine whether maraviroc has a viable target.

04

Dose maraviroc according to the complete CYP3A and renal context.

05

Explain fostemsavir conversion, gp120 binding, administration, interaction, and safety constraints.

06

Plan ibalizumab loading, maintenance, administration, missed-dose recovery, and reaction monitoring.

07

Teach enfuvirtide reconstitution, subcutaneous delivery, storage, site rotation, and toxicity response.

08

Construct an optimized background regimen from cumulative resistance and treatment history.

09

Preserve HBV treatment and use current pregnancy guidance during regimen reconstruction.

10

Close selection with virologic response, safety, access, and delivery ownership.

192.01

Lesson

Map the Entry Sequence Before Choosing the Drug

HIV-1 entry is an ordered molecular process. Each therapy blocks a different event, so a class label alone is not enough to predict activity, resistance, or delivery.

What to learn
  • gp120
  • CD4
  • CCR5 and CXCR4
  • gp41
  • Membrane fusion
Entry sequenceFollow the virus to the membrane
01gp120 to CD4Attachment

Carry this evidence forward.

02CCR5 or CXCR4Coreceptor

Carry this evidence forward.

03gp41 refoldingMembrane pull

Carry this evidence forward.

04FusionCytoplasmic entry

Own the next clinical action.

Begin with attachment

Envelope gp120 first engages CD4. This interaction changes gp120 conformation and exposes a coreceptor-binding surface.

Engage a coreceptor

The virus then uses CCR5 or CXCR4. Maraviroc allosterically blocks host CCR5, so it has no activity when detectable virus can enter through CXCR4.

Trigger fusion

Coreceptor binding enables gp41 to refold and draw viral and cellular membranes together. Enfuvirtide interrupts this gp41 fusion machinery.

Distinguish the other targets

Fostemsavir becomes temsavir and binds viral gp120 before CD4 attachment. Ibalizumab binds domain 2 of host CD4 after attachment and blocks downstream entry changes without depleting CD4 cells.

Quick check

0 of 1 answered
01Which pairing correctly matches an agent to its entry target?
Answer every question to submit.
192.02

Lesson

Build the Regimen From Cumulative Evidence

Entry and attachment inhibitors are most often considered when resistance, intolerance, or safety limits conventional options. Novel action does not make monotherapy safe.

What to learn
  • Virologic failure
  • Cumulative genotype
  • Phenotype
  • Optimized background regimen
  • Fully active drug
Regimen reconstructionProtect every remaining active mechanism
01HistoryAll prior ART

Carry this evidence forward.

02SusceptibilityGenotype and phenotype

Carry this evidence forward.

03Active partnersPrefer two or more

Carry this evidence forward.

04Early HIV RNA4 to 8 weeks

Own the next clinical action.

Confirm failure and its cause

Review HIV RNA trajectory, adherence, dispensing, food requirements, interactions, tolerability, and access before assigning resistance.

Read resistance cumulatively

A current plasma genotype may not display archived substitutions after drug pressure changes. Combine every prior genotype, phenotype, treatment response, and exposure.

Avoid functional monotherapy

Current guidance prefers at least two, and when possible three, fully active agents in a new regimen. Adding one active drug to a failing regimen can rapidly sacrifice that drug.

Monitor the new plan early

Measure HIV RNA before the change and within 4 to 8 weeks. Incomplete response should trigger immediate assessment of delivery, exposure, companion activity, and resistance.

Quick check

0 of 1 answered
01What is the central error in adding fostemsavir alone to a failing regimen?
Answer every question to submit.
192.03

Lesson

Verify the CCR5 Door Before Using Maraviroc

Maraviroc is a host-directed CCR5 antagonist. It is active only when the patient's HIV-1 population depends on CCR5 without detectable CXCR4 use.

What to learn
  • CCR5
  • CXCR4
  • Dual or mixed tropism
  • Allosteric antagonist
  • Tropism assay
Host coreceptorVerify the CCR5 door
01Tropism assayBefore selection

Carry this evidence forward.

02CCR5 onlyNo CXCR4 detected

Carry this evidence forward.

03MVC binds hostAllosteric change

Carry this evidence forward.

04Entry blockedgp120 cannot engage

Own the next clinical action.

Test before selection

Obtain a coreceptor tropism assay whenever maraviroc is being considered. A CCR5-tropic result establishes a necessary target, not a guarantee that the complete regimen will succeed.

Understand the allosteric effect

Maraviroc binds within CCR5 and changes its conformation so gp120 cannot complete productive coreceptor engagement. It does not bind gp120 or block CXCR4.

Interpret dual or mixed virus

If the assay detects CXCR4-using or dual or mixed virus, maraviroc is not an active option. A minority population can become clinically visible under CCR5 blockade.

Reassess persistent viremia

Failure can reflect nonadherence, inadequate companion activity, interactions, or a change in detectable tropism. Reconstruct the full mechanism rather than assuming a single cause.

Quick check

0 of 1 answered
01Which result supports considering maraviroc?
Answer every question to submit.
192.04

Lesson

Dose Maraviroc Inside the Interaction System

Maraviroc exposure changes with CYP3A inhibition, induction, renal function, and hepatic function. The interaction list is part of the dose.

What to learn
  • CYP3A
  • Renal impairment
  • Orthostasis
  • Hepatotoxicity
  • Hypersensitivity
Exposure systemDose from interactions and organs
01CYP3AInhibitor or inducer

Carry this evidence forward.

02KidneyCrCl and dialysis

Carry this evidence forward.

03Blood pressureOrthostasis

Carry this evidence forward.

04Liver and rashUrgent pattern

Own the next clinical action.

Use interaction-based adult dosing

Current NIH tables use 150 mg twice daily with strong CYP3A inhibition, 300 mg twice daily without a strong inhibitor or inducer, and 600 mg twice daily with a strong inducer and no strong inhibitor when otherwise appropriate.

Join renal and interaction data

With creatinine clearance below 30 mL/min or hemodialysis, potent inhibitors or inducers can make use inappropriate. Without those modifiers, monitor closely and reduce from 300 mg to 150 mg twice daily if postural hypotension develops.

Recognize orthostasis

Dizziness and orthostatic hypotension require positional blood pressure, volume, fall-risk, renal, and antihypertensive assessment.

Act on hepatic allergy patterns

Hepatotoxicity may be preceded by rash, fever, eosinophilia, edema, or other systemic allergy features. Stop and urgently evaluate a compatible presentation rather than treating each sign in isolation.

Quick check

0 of 1 answered
01A patient takes a strong CYP3A inhibitor and otherwise qualifies for maraviroc. What adult dose pattern is generally used?
Answer every question to submit.
192.05

Lesson

Block gp120 Attachment With Fostemsavir

Fostemsavir is a prodrug converted to temsavir. Temsavir binds gp120 and prevents HIV-1 from attaching to CD4 at the first receptor step.

What to learn
  • Fostemsavir
  • Temsavir
  • gp120
  • Extended release
  • Strong inducer
gp120 attachmentLock the viral envelope before CD4
01FostemsavirProdrug

Carry this evidence forward.

02TemsavirActive moiety

Carry this evidence forward.

03gp120 lockedViral target

Carry this evidence forward.

04Attachment stopsBefore CD4

Own the next clinical action.

Place the mechanism

Temsavir binds a conserved region of gp120 and stabilizes a conformation that cannot productively engage CD4. This differs from maraviroc's host CCR5 target and ibalizumab's host CD4 target.

Use the labeled regimen

Adults take 600 mg by mouth twice daily with or without food. Swallow the extended-release tablet whole and do not chew, crush, or split it.

Reject strong induction

Strong CYP3A inducers can markedly lower temsavir exposure. Contraindicated examples include rifampin, carbamazepine, phenytoin, enzalutamide, mitotane, and St. John's wort.

Monitor cardiac and hepatic context

Nausea is common. Consider QTc risk with preexisting heart disease or other QT-prolonging therapy, and monitor transaminase or bilirubin changes, especially with HBV or HCV coinfection.

Quick check

0 of 1 answered
01Which instruction is correct for fostemsavir?
Answer every question to submit.
192.06

Lesson

Block Post-Attachment Entry With Ibalizumab

Ibalizumab-uiyk is a humanized monoclonal antibody that binds domain 2 of CD4 and blocks post-attachment entry. Its delivery and missed-dose rules are part of its pharmacology.

What to learn
  • CD4 domain 2
  • Monoclonal antibody
  • Loading dose
  • IV infusion
  • IV push
CD4 post-attachmentBlock the next conformational step
01Load 2,000 mgIV start

Carry this evidence forward.

02CD4 domain 2Host target

Carry this evidence forward.

03Entry arrestedAfter attachment

Carry this evidence forward.

04800 mg every 2 weeksMaintain exposure

Own the next clinical action.

Understand selective CD4 binding

Ibalizumab binds away from major MHC class II interaction sites. It interferes with the conformational steps required for entry without acting as a CD4-depleting therapy.

Load and maintain

Give a 2,000 mg loading dose, then 800 mg every 2 weeks. Current labeling permits diluted IV infusion or undiluted IV push with dose-specific minimum administration times.

Recover a missed maintenance dose

When a maintenance dose is delayed by 3 days or more, give another 2,000 mg loading dose, then resume 800 mg every 2 weeks.

Observe and differentiate reactions

Monitor for hypersensitivity, infusion reactions, and anaphylaxis. Diarrhea, dizziness, nausea, and rash are common, while later inflammatory symptoms may represent immune reconstitution rather than an immediate infusion reaction.

Quick check

0 of 1 answered
01What should happen when an ibalizumab maintenance dose is delayed by at least 3 days?
Answer every question to submit.
192.07

Lesson

Interrupt gp41 Fusion With Enfuvirtide

Enfuvirtide is a peptide fusion inhibitor delivered subcutaneously twice daily. Technique, site reactions, storage, and treatment burden determine whether in vitro activity becomes reliable exposure.

What to learn
  • gp41
  • Fusion inhibitor
  • Subcutaneous injection
  • Reconstitution
  • Site rotation
gp41 fusionKeep the membranes apart
01gp41 exposedAfter coreceptor

Carry this evidence forward.

02T-20 bindsHeptad repeat

Carry this evidence forward.

03Bundle blockedNo membrane pull

Carry this evidence forward.

04No fusionNo entry

Own the next clinical action.

Stop the fusion bundle

Enfuvirtide binds the gp41 heptad repeat region and prevents the conformational bundle that pulls the viral and cellular membranes together.

Use the adult regimen

Adults receive 90 mg subcutaneously twice daily. Rotate the abdomen, anterior thighs, and posterior upper arms while avoiding scarred, inflamed, or repeatedly used sites.

Control preparation and storage

Reconstitute carefully without shaking. Refrigerate a prepared dose and use it within 24 hours. Teach inspection, labeling, transport, and sharps disposal.

Manage expected and serious harm

Most patients develop injection-site pain, erythema, induration, nodules, cysts, pruritus, or ecchymosis. Evaluate infection separately. Assess respiratory symptoms promptly because bacterial pneumonia was more frequent in trials, and never rechallenge after compatible systemic hypersensitivity.

Quick check

0 of 1 answered
01What is the most important practical limitation of enfuvirtide?
Answer every question to submit.
192.08

Lesson

Design Delivery That Can Survive Real Life

These drugs span twice-daily oral therapy, every 2 week IV treatment, and twice-daily self-injection. Susceptibility is irrelevant if the delivery pathway repeatedly fails.

What to learn
  • Access
  • Infusion
  • Injection skill
  • Storage
  • Missed dose
Exposure deliveryMake the route survivable
01Oral BIDMVC and FTR

Carry this evidence forward.

02IV every 2 weeksIBA

Carry this evidence forward.

03SC BIDT-20

Carry this evidence forward.

04Continuity proofRefills and visits

Own the next clinical action.

Compare the routes

Maraviroc and fostemsavir require twice-daily oral adherence. Ibalizumab requires reliable IV access every 2 weeks. Enfuvirtide requires repeated reconstitution and subcutaneous technique.

Assess the human workflow

Evaluate transportation, work schedule, dexterity, vision, refrigeration, housing, privacy, insurance, caregiver support, and the burden of visible injection sites.

Prevent predictable gaps

Book the next infusion before departure, establish a late-dose pathway, teach missed oral doses, and create travel and storage plans before a disruption occurs.

Measure delivery, not intention

Use refill history, infusion attendance, injection-site review, teach-back, and HIV RNA. A stated plan does not prove exposure.

Quick check

0 of 1 answered
01Which factor can make ibalizumab a poor practical fit despite predicted viral activity?
Answer every question to submit.
192.09

Lesson

Protect the Whole Regimen During Recovery

Safety surveillance must distinguish drug toxicity, hypersensitivity, infusion reactions, infection, IRIS, HBV reactivation, and failure. One symptom can represent very different mechanisms.

What to learn
  • IRIS
  • HBV
  • Pregnancy
  • HIV RNA
  • Toxicity
Mechanism of symptomsSeparate toxicity from recovery
01Time courseImmediate or delayed

Carry this evidence forward.

02HIV RNAFalling or rising

Carry this evidence forward.

03Organ dataLiver, BP, sites

Carry this evidence forward.

04Clinical responseToxicity, IRIS, failure

Own the next clinical action.

Recognize immune reconstitution

A rapid virologic response can unmask or worsen inflammation from an infection or autoimmune condition. Evaluate the underlying process instead of assuming the new ART is failing.

Preserve HBV suppression

None of these entry agents treats HBV. Continue tenofovir-based HBV-active ART or another fully suppressive HBV plan when rebuilding HIV therapy.

Use current pregnancy guidance

Do not use obsolete pregnancy letters. Maraviroc, fostemsavir, ibalizumab, and enfuvirtide have different evidence and current recommendations, so consult the latest perinatal guidance for the exact agent.

Assign monitoring ownership

Name who checks HIV RNA, liver tests, interaction changes, infusion or injection problems, adherence, pregnancy considerations, and urgent symptoms. Complex salvage therapy cannot rely on passive follow-up.

Quick check

0 of 1 answered
01Why must HBV-active therapy be preserved when adding an entry inhibitor?
Answer every question to submit.
192.10

Lesson

Choose the Target, Regimen, and Delivery Together

A successful entry-inhibitor plan aligns viral biology, cumulative resistance, companion activity, patient physiology, route, interaction environment, and access.

What to learn
  • Target
  • Susceptibility
  • Complete ART
  • Feasibility
  • Follow-up
Clinical synthesisAlign target, regimen, person, and delivery
01VirusTropism and resistance

Carry this evidence forward.

02Active ARTProtect the novel drug

Carry this evidence forward.

03PersonSafety and feasibility

Carry this evidence forward.

04Follow-upResponse ownership

Own the next clinical action.

Verify the target

Confirm HIV-1, tropism when maraviroc is considered, cumulative resistance, prior entry-agent exposure, and evidence supporting activity.

Construct complete ART

Prefer at least two and when possible three fully active agents. Preserve HBV treatment and avoid adding a single active drug to ongoing replication.

Fit safety and delivery

Integrate renal and hepatic function, QT or orthostatic risk, pregnancy, interactions, infusion access, injection skill, storage, and preference.

Close the feedback loop

Measure HIV RNA early, monitor agent-specific toxicity, verify administration, and have a defined response for delay, reaction, access loss, or incomplete suppression.

Quick check

0 of 1 answered
01Which plan best uses an entry inhibitor?
Answer every question to submit.

Module test

Check the connections.

Each attempt draws 10 questions from the complete 136 question bank.

136 questions in this module bank10 questions per attempt

Each attempt draws a fresh set and rearranges the answer choices.

References

Current clinical foundation.

Lecture material was synthesized with the following contemporary guidance. Verify local policy and current guidance before applying clinical information.

  1. NIH Antiretroviral Drug Characteristics Tables
  2. NIH Virologic Failure and Antiretroviral Options
  3. NIH Drug Resistance Testing
  4. NIH Viral Load and CD4 Monitoring
  5. NIH Renal and Hepatic Dosing Table
  6. NIH Perinatal Antiretroviral Safety Table
  7. FDA Rukobia Prescribing Information
  8. FDA Trogarzo Prescribing Information
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