Enfuvirtide

Chemical Identity

Property	Value
Chemical Formula	C204H301N51O64
Molecular Weight	4492 Da
CAS Number	159519-65-0
Peptide Class	Synthetic Linear Peptide (36 amino acids)
Sequence	YTSLIHSLIEESQNQQEKNEQELLELDKWASLWNWF
Route	SC injection

Structure

Enfuvirtide (T-20, Fuzeon) is a synthetic 36-amino acid peptide corresponding to a region of the HIV-1 gp41 transmembrane glycoprotein. It mimics the C-terminal heptad repeat region of gp41 that binds to the N-terminal heptad repeat, preventing the conformational change required for membrane fusion.

Mechanism of Action

During HIV entry, gp41 undergoes a conformational change exposing the N-terminal and C-terminal heptad repeat regions, which fold into a six-helix bundle that drives membrane fusion. Enfuvirtide binds to the N-terminal heptad repeat, preventing six-helix bundle formation and blocking the final step of viral-cell membrane fusion.

Clinical Applications

• HIV-1 infection: Treatment-experienced patients with multidrug-resistant virus (Fuzeon)
• TROTORO and TORO trials: Significant viral load reduction in heavily pretreated patients
• Salvage therapy: When other antiretroviral options exhausted
• Bridge therapy: While awaiting other treatment options

Pharmacokinetics

• Half-life: 3.8 hours
• Tmax: 4-8 hours (SC)
• Bioavailability: 84% (SC)
• Metabolism: Proteolytic degradation
• Dosing: 90 mg SC twice daily
• Route: SC injection (thigh, abdomen, upper arm)

Safety and Side Effects

Injection site reactions (98%, most common reason for discontinuation), bacterial pneumonia (increased risk), insomnia, depression, peripheral neuropathy, and eosinophilia. Requires proper injection technique training.

References

• Lalezari, J.P., et al. (2003). T-20 versus optimized background regimen for HIV. New England Journal of Medicine, 348, 2175-2185.
• Kilby, J.M., et al. (1998). Peptide T-20 inhibitor of HIV-1 fusion. Nature Medicine, 4, 1302-1307.