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Enfuvirtide
Systematic (IUPAC) name
Acetyl-YTSLIHSLIEESQNQ QEKNEQELLELDKWASLWNWF-amide
Identifiers
CAS number	159519-65-0
ATC code	J05AX07
PubChem	16130199
DrugBank	BTD00106
Chemical data
Formula	C202H298N50O64
Mol. mass	4492.1 g/mol
Pharmacokinetic data
Bioavailability	84.3% (SC)
Protein binding	92%
Metabolism	Hepatic
Half life	3.8 hours
Excretion	unknown
Therapeutic considerations
Pregnancy cat.	B2 (Au), B (U.S.)
Legal status	S4 (Au), POM (UK), ℞-only (U.S.)
Routes	Subcutaneous (SC)

Enfuvirtide (INN) is an HIV fusion inhibitor, the first of a novel class of antiretroviral drugs used in combination therapy for the treatment of HIV-1 infection. It is marketed under the trade name Fuzeon (Roche).

Enfuvirtide therapy costs an estimated USD$25,000 per year in the United States. Its cost and inconvenient dosing regimen are factors behind its use as a reserve, for "salvage" therapy in patients with multi-drug resistant HIV.

Contents 1 Structural Formula 2 History 3 Pharmacology 3.1 Mechanism of action 3.2 Microbiology 4 Clinical use 4.1 Indications 4.2 Dosage forms 4.3 Adverse effects 5 References

Ac-Tyr-Thr-Ser-Leu-Ile-His-Ser-Leu- Ile-Glu-Glu-Ser-Gln-Asn-Gln-Gln-Glu- Lys-Asn-Glu-Gln-Glu-Leu-Leu-Glu- Leu-Asp-Lys-Trp-Ala-Ser-Leu-Trp-Asn- Trp-Phe-NH₂

Enfuvirtide originated at Duke University, where researchers formed a pharmaceutical company known as Trimeris. Trimeris began development on enfuvirtide in 1996 and initially designated it T-20. In 1999, Trimeris entered into partnership with Hoffmann-La Roche to complete the development of the drug. It was approved by the U.S. Food and Drug Administration (FDA) on March 13, 2003 as the first HIV fusion inhibitor, a new class of antiretroviral drugs. It was approved on the basis of two studies (TORO 1 and TORO 2) which compared the effect of optimized regimens of antiretroviral medication with and without the addition of enfuvirtide on serum viral load.

Enfuvirtide works by disrupting the HIV-1 molecular machinery at the final stage of fusion with the target cell, preventing uninfected cells from becoming infected. A biomimetic peptide, enfuvirtide was rationally designed to mimic components of the HIV-1 fusion machinery and displace them, preventing normal fusion. Drugs that disrupt fusion of virus and target cell are termed entry inhibitors or Fusion inhibitors. HIV binds to host cell receptor CD4+ by the protein GP120; upon binding, GP120 deforms allowing the viral protein GP41 to embed itself into the host cell's plasma membrane, entry inhibitors bind to GP41 preventing the creation of an entry pore for the capsid of the virus keeping it out of the cell. [1]

Enfuvirtide is considered to be active against HIV-1 only. Low activity against HIV-2 isolates has been demonstrated in vitro.^[1]

Variable susceptibility to enfuvirtide has been observed in clinical isolates, with acquired resistance the result of a mutated 10 amino acid motif in viral gp41. Primary resistance, however, has yet to be observed.^[2]

Enfuvirtide is indicated for the treatment of HIV-1 infection, in combination therapy with other antiretrovirals, in patients where all other treatments have failed.^[3]

By virtue of its peptide nature, enfuvirtide is marketed in injectable form. The lyophilised enfuvirtide powder must be reconstituted by the patient and administered twice daily by subcutaneous injection.

Common adverse drug reactions (≥1% of patients) associated with enfuvirtide therapy include: injection site reactions (pain, hardening of skin, erythema, nodules, cysts, itch; experienced by nearly all patients, particularly in the first week), peripheral neuropathy, insomnia, depression, cough, dyspnoea, anorexia, arthralgia, infections (including bacterial pneumonia) and/or eosinophilia. Various hypersensitivity reactions occur infrequently (0.1–1% of patients), symptoms of which include rash, fever, nausea, vomiting, chills, rigors, hypotension, elevated hepatic transaminases; and possibly more severe reactions including respiratory distress, glomerulonephritis and/or anaphylaxis – rechallenge is not recommended.^[3]

v • d • e Antivirals used against HIV (HAART) (primarily J05)
Nucleoside & Nucleotide Reverse Transcriptase Inbitors (NRTI)	Abacavir (ABC) • Didanosine • Emtricitabine° • Lamivudine (3TC)° • Stavudine • Zidovudine (AZT)° • Tenofovir° • Apricitabine† • Stampidine† • Zalcitabine‡
Non-Nucleoside Reverse Transcriptase Inhibitiors (NNRTI)	Efavirenz° • Nevirapine • Etravirine† • Rilpivirine† • Loviride‡ • Delavirdine‡
Protease Inhibitors (PI)	Atazanavir • Darunavir • Fosamprenavir • Lopinavir° • Nelfinavir • Ritonavir • Saquinavir • Tipranavir • Amprenavir‡ • Indinavir‡
Entry/fusion inhibitors	Enfuvirtide • Maraviroc • Vicriviroc†
Integrase inhibitors	Raltegravir • Elvitegravir†
Maturation inhibitors	Bevirimat† • Vivecon™†
Combined formulations	Combivir • Atripla • Trizivir • Truvada • Kaletra • Epzicom
Other & experimental agents	Foscarnet • Synergistic enhancers • Epigallocatechin gallate • Portmanteau inhibitors • Globoidnan A • Griffithsin • Diarylpyrimidines • Calanolide A
†Undergoing clinical trials, not FDA approved. ‡Formerly or rarely used agent. °Preferred 1st line agent.