Maraviroc

Maraviroc is an oral CCR5 co-receptor antagonist used in treatment-experienced adults and children infected only with CCR5-tropic HIV-1. It blocks a human receptor rather than a viral enzyme, so it works only after a tropism test shows no CXCR4 or dual-mixed virus. The dose changes with the interacting drug, and it carries a boxed warning for hepatotoxicity with allergic features.

Class. CCR5 antagonist; entry inhibitor.

Mechanism. Binds the CCR5 receptor on CD4 cells and blocks the interaction with the viral gp120 envelope protein, so the virus cannot enter the cell. It is inactive against CXCR4-tropic virus.

Pharmacokinetics. Oral bioavailability about 33%, not affected by food. Half life 14 to 18 hours. Metabolised by CYP3A4 and a P-glycoprotein substrate, so inhibitors raise and inducers lower levels.

CCR5-tropic HIV-1 infection, treatment-experienced (adults and children 30 kg or more). - 300 mg orally twice daily with no interacting drug. - 150 mg twice daily with strong CYP3A inhibitors (boosted protease inhibitors except tipranavir, cobicistat, itraconazole, clarithromycin). - 600 mg twice daily with inducers (efavirenz, etravirine without a boosted protease inhibitor, rifampicin, carbamazepine, phenytoin).

Children (2 years and over, 10 kg or more). Weight-banded dosing with the same interaction adjustments.

Loading dose, maintenance dose and titration. Not applicable. Maximum: 600 mg twice daily.

Main alternatives. Integrase inhibitors and boosted protease inhibitors, chosen by resistance results.

Contraindications. Hypersensitivity; dual or CXCR4-tropic virus; severe kidney impairment with strong CYP3A inhibitors; St John’s wort.

Serious adverse effects. Hepatotoxicity preceded by rash, fever or eosinophilia (allergic features), postural hypotension, cardiovascular events (uncommon), severe skin reactions, and immune reconstitution syndrome.

Common adverse effects. Cough, dizziness, fever, rash, abdominal pain and upper respiratory infection.

Interactions. Strong CYP3A4 inhibitors lower the dose to 150 mg twice daily, and inducers raise it to 600 mg twice daily; strong inhibitors in kidney impairment raise the risk of postural hypotension.

Common prescribing errors. Prescribing without a tropism test, forgetting the dose change with a booster or efavirenz, and missing early rash.

Special groups. - Pregnancy: limited data; use only if needed. - Breastfeeding: avoid. - Children: from 2 years and 10 kg. - Older adults: usual dose. - Kidney impairment: no adjustment unless CrCl is under 30 mL/min with a strong CYP3A inhibitor, when it is avoided. - Liver impairment: caution; avoid in severe disease.

Regional points. Phenotypic or genotypic tropism testing is rarely available in East Africa, so use is limited to specialist third-line care.

Formulations. Tablets 150 mg and 300 mg; oral solution 20 mg/mL (where available).

Administration. Twice daily with or without food.

Baseline. Tropism result, liver tests, hepatitis B and C status, blood pressure, interaction check.

Monitoring. Liver tests at 2, 4 and 12 weeks and then every 3 months; blood pressure; viral load at 3 and 6 months.

Stopping thresholds. Stop for rash with fever, eosinophilia or raised liver enzymes, or for ALT over 3 times the upper limit of normal with symptoms, or over 5 times without.

Referral and escalation. Specialist review for all patients and for any liver injury.