Enfuvirtide

Enfuvirtide is a subcutaneous peptide fusion inhibitor used in heavily treatment-experienced patients with multidrug-resistant HIV-1, always with other active drugs. It is the only fusion inhibitor and has no interactions through liver enzymes, but its twice-daily injections cause local reactions in nearly all patients, which limits use.

Class. Fusion inhibitor; entry inhibitor.

Mechanism. Binds the HR1 region of viral gp41 and prevents conformational change needed for fusion of viral and cell membranes. Mutations in gp41 cause resistance.

Pharmacokinetics. Subcutaneous bioavailability about 84%. Half life about 3.8 hours. Broken down by proteolysis into amino acids; not metabolised by liver enzymes.

Multidrug-resistant HIV-1 infection (adults). 90 mg (1 mL) subcutaneously twice daily, with other active drugs.

Children 6 to 16 years. 2 mg/kg subcutaneously twice daily (maximum 90 mg in each dose), by weight bands.

Loading dose, maintenance dose and titration. Not applicable. Maximum: 180 mg daily.

Main alternatives. Fostemsavir, ibalizumab, integrase inhibitors and boosted protease inhibitors chosen by resistance results.

Contraindications. Hypersensitivity.

Serious adverse effects. Hypersensitivity reactions (rash, fever, hypotension), bacterial pneumonia (higher in smokers and low CD4 counts), eosinophilia, immune complex reactions and glomerulonephritis (rare), and Guillain-Barré syndrome (rare).

Common adverse effects. Injection-site reactions (pain, erythema, nodules, cysts) in almost all patients, diarrhoea, nausea and fatigue.

Interactions. None of clinical importance.

Common prescribing errors. Using it as the only active drug, injecting into the same site repeatedly, and missing signs of pneumonia.

Special groups. - Pregnancy: limited data. - Breastfeeding: avoid. - Children: from 6 years; weight-banded. - Older adults: usual dose. - Kidney impairment: no adjustment at CrCl 35 mL/min or more; on dialysis, usual dose. - Liver impairment: no adjustment.

Formulations. Powder for injection 108 mg vial (90 mg delivered in each dose).

Administration. Reconstitute with 1.1 mL sterile water, allow it to dissolve (up to 45 minutes), and inject into the upper arm, anterior thigh or abdomen, rotating sites. Use the solution within 24 hours if refrigerated.

Baseline. Resistance result, chest examination, full blood count, liver tests, smoking history.

Monitoring. Injection sites at each visit; respiratory symptoms; full blood count; viral load at 3 and 6 months.

Stopping thresholds. Stop for hypersensitivity, pneumonia needing admission, or glomerulonephritis.

Referral and escalation. Specialist review for all patients and for any hypersensitivity or respiratory illness.