Ibalizumab

Ibalizumab is an intravenous humanised monoclonal antibody against CD4, a post-attachment entry inhibitor used in heavily treatment-experienced adults with multidrug-resistant HIV-1. It does not block CD4 function and has no cross-resistance or drug interactions, but it needs clinic infusions and is available in few places.

Class. Monoclonal antibody; CD4-directed post-attachment HIV-1 inhibitor.

Mechanism. Binds domain 2 of CD4 on host cells and blocks the conformational change needed after attachment for viral entry.

Pharmacokinetics. Intravenous only. Elimination is by receptor-mediated clearance, with a half life about 3 days at the maintenance dose. It does not use liver enzymes or the kidney.

Multidrug-resistant HIV-1 infection, heavily treatment-experienced (adults). - Loading: 2000 mg intravenously once, over at least 30 minutes. - Maintenance: 800 mg intravenously every 2 weeks, over 15 to 30 minutes (or by intravenous push over 30 seconds). - Given with an optimised background regimen that includes other active drugs.

Missed dose. If more than 3 days late, give another 2000 mg loading dose and resume the 800 mg schedule.

Loading dose, maintenance dose and titration. Loading dose 2000 mg once, then 800 mg every 2 weeks. Maximum: 2000 mg in a single dose.

Main alternatives. Fostemsavir or enfuvirtide.

Contraindications. Hypersensitivity.

Serious adverse effects. Immune reconstitution syndrome, infusion-related reactions, and severe rash (rare).

Common adverse effects. Diarrhoea, dizziness, nausea and rash.

Interactions. None of clinical importance.

Common prescribing errors. Using without another active drug, and late maintenance doses without a reload.

Special groups. - Pregnancy: limited data. - Breastfeeding: avoid. - Children: not established. - Older adults: usual dose. - Kidney impairment: no adjustment. - Liver impairment: no adjustment.

Formulations. Solution for infusion 200 mg/1.33 mL vial (150 mg/mL).

Administration. Dilute in 250 mL of 0.9% sodium chloride for loading; observe for 1 hour after the first dose.

Baseline. Resistance result, CD4 count, viral load, hypersensitivity history.

Monitoring. Viral load at 1 and 3 months and then every 3 months; infusion reactions.

Stopping thresholds. Stop for severe hypersensitivity or infusion reaction.

Referral and escalation. Specialist review for every patient.