Enfuvirtide Peptide: Structure, Research & Science Guide

By The Peptides Codex Editorial TeamReviewed September 8, 2026

Page data last changed: 2026-10-05. Chemistry registry snapshot: 2026-10-01. Registry refreshes and identity assessments are separate from scientific content review.

Length

36 aa

Class

Synthetic HIV fusion-inhibitor peptide

Function

Binds the HR1 region of HIV-1 gp41 and blocks fusion of the viral and cell membranes

Context

Approved (2003) as the first HIV fusion inhibitor, for treatment-experienced patients with multidrug-resistant HIV-1, given subcutaneously twice daily

The first drug of an entire antiretroviral class — and a 36-residue peptide that must be injected twice a day because the gut destroys it.

Also known as: T-20 · DP-178 · pentafuside · Fuzeon (brand)

Part of the Foundational & therapeutic peptides cluster

Overview

Enfuvirtide (T-20, Fuzeon) is a synthetic 36-amino-acid peptide that blocks HIV-1 entry by binding the gp41 envelope glycoprotein and preventing fusion of the viral and cellular membranes. The first of the fusion-inhibitor class, it was approved in 2003 for treatment-experienced adults with multidrug-resistant virus after two randomised trials showed significantly lower HIV RNA and higher CD4 counts at 24 and 48 weeks when added to optimised background therapy. It is unstable in the gut and is given subcutaneously twice daily.

Source & context

Biological / chemical source: Synthetic 36-residue peptide corresponding to a segment of the HIV-1 envelope glycoprotein gp41

Primary research or clinical context: Approved (2003) as the first HIV fusion inhibitor, for treatment-experienced patients with multidrug-resistant HIV-1, given subcutaneously twice daily

What enfuvirtide is

Enfuvirtide — development codes T-20 and DP-178, originally called pentafuside, marketed as Fuzeon — is a synthetic peptide of 36 amino acids that mimics a segment of the HIV-1 envelope glycoprotein gp41 (Machala, Klinická Mikrobiologie a Infekční Lékařství 2004). Developed jointly by Trimeris and Roche, it was the first of a new class of antiretroviral agents, the fusion inhibitors, which block HIV-1 entry into the host cell (Lalezari and Luber, Drugs of Today 2004). PubChem records it as compound 16130199, CAS 159519-65-0.

Mechanism: stopping the fusion step

HIV enters a cell in stages. The surface glycoprotein gp120 attaches to CD4 and a chemokine co-receptor; the transmembrane glycoprotein gp41 then undergoes a conformational change that pulls the viral and cell membranes together (Chen et al., Expert Opinion on Investigational Drugs 2002). Enfuvirtide binds the HR1 domain of gp41 and blocks that fusion (Machala 2004), so the virus never enters. Because the mechanism is unlike that of every other class, it retains activity against virus resistant to reverse-transcriptase and protease inhibitors, which was its reason for existing (Lazzarin, Expert Opinion on Pharmacotherapy 2005).

Clinical evidence

In two randomised trials in adults with advanced HIV infection, enfuvirtide 90 mg subcutaneously twice daily added to optimised background antiretroviral therapy significantly reduced plasma HIV RNA compared with background therapy alone after 24 weeks, an effect maintained through 48 weeks; the increase in CD4+ cell count was also significantly greater with enfuvirtide at both time points (Dando and Perry, Drugs 2003). Phase 2 and 3 studies confirmed effectiveness and safety in adult and paediatric patients, with only mild or moderate adverse events for most (Lalezari and Luber 2004). Later trials examined intensification with enfuvirtide in treatment-naïve patients (NCT00302822) and switching from enfuvirtide to raltegravir (NCT00454337).

Pivotal findings summarised in the cited reviews
Endpoint	Result
Regimen studied	90 mg subcutaneous twice daily + optimised background therapy
Plasma HIV RNA at 24 weeks	Significantly reduced vs background therapy alone
Durability	Antiviral effect maintained through 48 weeks
CD4+ cell count	Significantly greater increase at 24 and 48 weeks

Resistance and limitations

HIV isolates with reduced susceptibility to enfuvirtide have been recovered from patients receiving it in combination with other antiretrovirals (Dando and Perry 2003), so it is used within an optimised regimen rather than alone. The peptide is not stable in the gastrointestinal tract and must be administered subcutaneously (Machala 2004), and its pharmacokinetics support twice-daily dosing (Lalezari and Luber 2004). Injection-site reactions are the characteristic tolerability issue; a 2021 case report describes enfuvirtide-induced cutaneous amyloidosis at injection sites (Sundharkrishnan et al., Cutis 2021). Enfuvirtide has not been associated with liver injury (LiverTox, NIDDK 2018).

Why a peptide, and how it is made

The drug is a peptide because its target is a peptide surface: only a chain that mimics gp41's own helix can occupy the HR1 groove. That choice carries the standard costs — no oral route, twice-daily injection, and a manufacturing burden that made enfuvirtide one of the most complex synthetic pharmaceuticals of its time. Solid-phase synthesis remains the primary method, but its chemical waste and cost rise steeply with peptide length, and a 2022 study reported producing enfuvirtide biosynthetically in Escherichia coli using a thermostable chaperone-based fusion partner, purified in part by heat denaturation of host proteins (Zenin et al., Biotechnology Reports 2022).

Place in therapy

Enfuvirtide was registered for salvage therapy in patients with multidrug-resistant virus for whom an effective combination of other antiretrovirals could not be constructed (Machala 2004). As integrase inhibitors and newer classes arrived, that niche narrowed; trials of switching from enfuvirtide to raltegravir reflect the transition. It remains an approved medicine and a landmark: proof that a synthetic peptide could become a first-in-class antiviral. It is not a research peptide and is not part of the grey market. This profile is educational and is not medical advice.

Structure & chemistry

Molecular identity & reference confidence

Source-supported reference

Reference values are taken from the cited molecular record or curated profile. A database match is not independent laboratory verification; modifications, counter-ions, and formulations can change the measured mass.

Molecular form: Linear 36-residue synthetic peptide derived from the gp41 sequence; not stable in the gastrointestinal tract, so administered subcutaneously
Species: Not established by this molecular identity audit
Termini (N / C): Not specified / Not specified

Average reference mass

Reference policy updated: 2026-10-05

IUPHAR/BPS source snapshot · 2026-10-01
PubChem molecular record · 2026-10-01

Molecular formula: C204H301N51O64
Average reference mass: ≈ 4,492
Receptors: Not a receptor ligand: binds the HR1 domain of HIV-1 gp41, preventing the conformational change that fuses viral and host membranes
Backbone: Linear 36-residue synthetic peptide derived from the gp41 sequence; not stable in the gastrointestinal tract, so administered subcutaneously
Status: Approved (2003) for treatment-experienced HIV-1 infection with multidrug resistance; the first fusion inhibitor

Identifiers

PubChem CID: 16130199
IUPHAR ligand: 4986
CAS RN: 159519-65-0
UNII: 19OWO1T3ZE

Chemistry values: curated profile, PubChem, IUPHAR/BPS Guide to Pharmacology · fetched 2026-10-01.

Clinical development snapshot

ClinicalTrials.gov lists 54 registered studies with “Enfuvirtide” as an intervention (snapshot 2026-10-01). A registry footprint is not evidence of efficacy or approval.

Registered studies

Highest phase reached

Phase 4

Active in latest 100

Most recent update

2026-08-10

Most recently updated studies
NCT	Title	Phase	Status	Updated
NCT05502341	Study to Compare Bictegravir/Lenacapavir Versus Current Therapy in People With HIV-1 Who Are Successfully Trea	Phase 3	active not recruiting	2026-08-10
NCT00302822	Intensification With Enfuvirtide in Naive HIV-infected Patients (ANRS130)	Phase 3	completed	2026-04-07
NCT01022476	Raltegravir in Patients With End Stage Liver Disease and in Transplant Recipients	Phase 2	completed	2026-04-06
NCT00454337	Efficacy and Tolerance of the Switch From Enfuvirtine to Raltegravir in Antiretroviral Therapy Regimen in HIV	Phase 3	completed	2026-04-06
NCT00120367	Early Intensification of Antiretroviral Therapy Including Enfuvirtide in HIV-1-Related Progressive Multifocal	Phase 2	completed	2026-04-02
NCT02302547	Trial to Evaluate the Interest of a Reductive Anti Retroviral Strategy Using Dual Therapy Inspite of Triple Th	Phase 3	completed	2025-12-26

See all on ClinicalTrials.gov →

Concentration math

Enfuvirtide — reconstitution calculator

Enter how much peptide is in the vial and how much diluent (e.g. bacteriostatic water) is added. The tool returns the resulting solution concentration — and, for any amount you type, the volume it corresponds to. This is educational arithmetic, not a dosing recommendation.

Reference form: Linear 36-residue synthetic peptide derived from the gp41 sequence; not stable in the gastrointestinal tract, so administered subcutaneouslyAverage reference mass: 4,492 Da

Peptide in vial (mg)

Diluent added (mL)

Syringe graduation

Solution concentration

5 mg/mL5,000 mcg/mL

Amount to measure (optional)

mcg

Enter an amount to see the volume it corresponds to.

Educational concentration mathematics only. This tool does not recommend a dose, amount, or protocol, and nothing here is medical advice. Many peptides are not authorized by Health Canada for human use — see our reconstitution and bacteriostatic-water guides for context.

Open the Enfuvirtide calculator on its own page →

Change log

Dated observations from the data pipeline (registry flags, trial footprints, identifiers) and editorial reviews of this profile.

2026-09-08IdentifiersCross-linked to IUPHAR ligand 4986 and PubChem CID 16130199.
2026-09-08TrialsClinicalTrials.gov snapshot added: 54 registered studies, highest phase 4.
2026-09-08EditorialProfile content reviewed and updated by the editorial team.

FAQ about Enfuvirtide

What is Enfuvirtide?+

What Canadian product status is recorded for Enfuvirtide?+

Canadian product status for Enfuvirtide has not been verified in this profile. No verified record here does not mean no authorization exists. Status depends on the product, formulation and use; consult Health Canada's product records.

What is the typical length of Enfuvirtide?+

Enfuvirtide is commonly described as approximately 36 amino acids (Synthetic HIV fusion-inhibitor peptide).

What is enfuvirtide?+

A synthetic 36-amino-acid peptide (T-20, Fuzeon) that blocks HIV-1 from fusing with cells by binding the gp41 envelope glycoprotein. It was the first HIV fusion inhibitor.

How does enfuvirtide work?+

It binds the HR1 domain of gp41 and prevents the conformational change that merges the viral and cell membranes, so the virus cannot enter.

Why is enfuvirtide injected?+

The peptide is unstable in the gastrointestinal tract, so it is given subcutaneously; its pharmacokinetics support twice-daily dosing.

What did the trials show?+

Added to optimised background therapy in treatment-experienced adults, enfuvirtide significantly lowered HIV RNA and raised CD4 counts at 24 and 48 weeks.

Is enfuvirtide still used?+

It remains approved but is reserved for multidrug-resistant HIV; newer oral classes have largely replaced it.

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References & further reading

Disclaimer: Educational content only. Not medical advice. Not instructions for human use. Research peptides and unapproved products may be restricted or illegal to market for human consumption in your jurisdiction. Consult qualified professionals and applicable law.

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