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

Dosage Protocols

The following reflects doses used in published research studies. This is not medical advice. Consult a qualified healthcare professional.

Beginner90 mg SC BID (adult standard)
Intermediate90 mg SC BID (adult standard)
AdvancedPediatric dosing: 2 mg/kg (max 90 mg) SC BID
Cycle DurationChronic use — continued as part of combination antiretroviral therapy

HIV fusion inhibitor. Used only as part of combination antiretroviral therapy in treatment-experienced patients with ongoing viral replication. Rotate injection sites to minimize injection site reactions.

Routes of Administration

Subcutaneous Injection ~84%

Inject into upper arm, anterior thigh, or abdomen. Rotate sites — injection site reactions occur in ~98% of patients (nodules, cysts, erythema).

Stacking Protocols

Popular research stacks involving Enfuvirtide (T-20):

Salvage Antiretroviral Regimen

Used in treatment-experienced HIV patients with multidrug-resistant virus. Combined with active agents from other classes to achieve virologic suppression. Clinical use only.

EnfuvirtideIntegrase inhibitor (raltegravir/dolutegravir)Protease inhibitor (darunavir/r)

Reconstitution

StorageReconstituted solution: use immediately or refrigerate 2-8°C and use within 24 hours

Tap vial for ~10 seconds, gently roll between palms for 10 seconds to avoid foaming. May take up to 45 minutes to dissolve fully.

Need exact syringe measurements?

Amino Acid Sequence

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 (36 AA)

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

Safety & Contraindications

This information is for educational purposes only. Consult a qualified healthcare provider before using any peptide.

Relative

Pregnancy / Lactation

Relative

Bleeding Disorders

Absolute

Active Skin Infection at Injection Site

FDA Safety Information

FDA labeling warns of injection-site reactions, hypersensitivity reactions, and increased bacterial pneumonia risk.

FDA Source: Bulk Drug Substances Safety Risks

Pharmacokinetics

Half-Life~3.8 hours
StorageStore unreconstituted vials at room temperature (15-30°C). After reconstitution: refrigerate 2-8°C, use within 24 hours.

Synergistic Compounds

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

Antiretroviral combination therapyEntry inhibitors (Maraviroc)

Learn More

References & Further Reading