Enfuvirtide

Summary

Enfuvirtide (T-20) is the first approved HIV fusion inhibitor, indicated for treatment-experienced adults and pediatric patients (≥6 years) with HIV-1 infection who have evidence of HIV-1 replication despite ongoing antiretroviral therapy. It is administered by twice-daily subcutaneous injection and is used in combination with other antiretroviral agents.

Mechanism of Action

Enfuvirtide is a 36-amino acid synthetic peptide that binds to the HR1 domain of the HIV-1 gp41 transmembrane glycoprotein, preventing the conformational change required for fusion of the viral envelope with the CD4+ T-cell membrane, thereby blocking viral entry into host cells.

Routes of Administration

Goals & Uses

• Prevention of HIV disease progressionDisease ModificationModerate
• Salvage therapy for multidrug-resistant HIVAntiretroviral SalvageHigh
• Reduction of HIV-1 viral loadAntiviral / Virologic SuppressionHigh
• Increase in CD4+ T-cell countImmunological RestorationHigh

Contraindications

• Treatment-naive HIV patientsClinical IndicationModerate
• Hypersensitivity to enfuvirtide or any excipientAllergy / HypersensitivityHigh

Adverse Effects

• Peripheral neuropathyNeurologicalUncommon
• Hypersensitivity reactionsImmunologicRare
• EosinophiliaHematologicUncommon
• Fatigue and insomniaGeneral / CNSCommon
• Injection site reactions (ISRs)Local / DermatologicCommon
• Bacterial pneumoniaInfectiousUncommon

Drug Interactions

• RifampicinLow
• SaquinavirLow
• RitonavirLow

Population Constraints

• PregnancyReproductive SafetyRelative
• Renal impairmentOrgan ImpairmentRelative
• Pediatric patients < 6 yearsAgeAbsolute
• Coagulation disorders / anticoagulant useHematologicRelative

Regulatory Status

• European UnionApprovedApproved: HIV-1 infection in treatment-experienced adults and children ≥6 years in combination with other antiretroviral medicinal productsApproved by EMA in 2003 under centralized procedure. Brand name Fuzeon. Marketing authorization held by Roche.
• United StatesApprovedApproved: HIV-1 infection in treatment-experienced adults and pediatric patients ≥6 years in combination with other antiretroviral agentsFDA approved March 13, 2003. Accelerated approval based on surrogate endpoints (viral load reduction). First fusion inhibitor approved.
• United KingdomApprovedApproved: HIV-1 infection in treatment-experienced adults and pediatric patients ≥6 years in combination with other antiretroviral agentsRetained approval post-Brexit under MHRA; consistent with EU label.

Approved by the FDA in March 2003 and by the EMA in 2003 under the brand name Fuzeon. Indicated only for treatment-experienced patients with detectable viral load on current antiretroviral regimens. Roche and Trimeris developed the compound jointly.

Evidence & Sources

No sources recorded yet.