Enfuvirtide (T-20)

Overview

Enfuvirtide (Fuzeon) is a synthetic 36-amino acid peptide HIV fusion inhibitor that was the first member of this antiretroviral drug class and remains the only peptide antiretroviral approved by the FDA (2003). Derived from the heptad repeat 2 (HR2) region of the HIV-1 gp41 transmembrane protein, enfuvirtide prevents HIV-1 from fusing with CD4+ T-cell membranes by competitively blocking the conformational change required for viral envelope-cellular membrane fusion. It is used in treatment-experienced patients with multidrug-resistant HIV-1 as part of combination antiretroviral therapy.

Mechanism of Action

HIV-1 entry requires sequential interactions: gp120 binds CD4 and co-receptor CCR5/CXCR4, causing gp41 to unfold and expose its fusion peptide (FP), which inserts into the target cell membrane. Two heptad repeat regions (HR1, HR2) of gp41 then fold together in a six-helix bundle structure that brings viral and cellular membranes into close apposition for fusion. Enfuvirtide, derived from HR2, binds HR1 before six-helix bundle formation, preventing the conformational change and inhibiting membrane fusion. This blocks viral entry without requiring intracellular drug access.

Potential Benefits

• First-in-class HIV fusion inhibitor
• Activity against multidrug-resistant HIV-1 (new mechanism)
• Effective in treatment-experienced patients
• No cross-resistance with other antiretroviral drug classes
• Additive/synergistic with other antiretrovirals in combination regimens

Research Dosage Notes

The following reflects doses used in published research studies. This is not medical advice.

90 mg (1 mL) SC twice daily into upper arm, thigh, or abdomen. Rotate injection sites.

Amino Acid Sequence

Side Effects & Safety

• Injection site reactions (virtually universal; nodules, cysts, ecchymosis)
• Increased bacterial pneumonia risk
• Hypersensitivity reactions (1-2% of patients)
• High cost and twice-daily injection burden

Synergistic Compounds

The following compounds have been studied alongside Enfuvirtide (T-20) for potential complementary or synergistic effects:

Related Peptides

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References & Further Reading

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