Elvitegravir

Elvitegravir is an oral integrase strand transfer inhibitor that is only available boosted with cobicistat, as a single tablet with emtricitabine and tenofovir alafenamide. It has a lower barrier to resistance than dolutegravir and many interactions through cobicistat. It is not advised in pregnancy because levels fall in the second and third trimesters.

Class. Integrase strand transfer inhibitor (boosted).

Mechanism. Binds the integrase active site and blocks strand transfer. The T66I, E92Q and Q148 mutations reduce susceptibility and also affect raltegravir.

Pharmacokinetics. Absorption improved by food. Half life about 9 hours with cobicistat. Metabolised by CYP3A4. Cobicistat inhibits CYP3A4 and CYP2D6 and also raises serum creatinine without true change in filtration.

HIV-1 infection (adults and children 25 kg or more). One tablet orally once daily with food, containing elvitegravir 150 mg, cobicistat 150 mg, emtricitabine 200 mg and tenofovir alafenamide 10 mg.

Children 14 to under 25 kg. A lower-strength tablet is used where licensed.

Dose adjustment for kidney function. CrCl 30 mL/min or more: no adjustment; under 30: not advised unless on dialysis.

Loading dose, maintenance dose and titration. Not applicable. Maximum: one tablet daily.

Main alternative. Dolutegravir or bictegravir regimens.

Contraindications. Hypersensitivity; co-administration with rifampicin, rifapentine, carbamazepine, phenytoin, phenobarbital, St John’s wort, ergot alkaloids, oral midazolam, triazolam, pimozide, lurasidone, simvastatin, lovastatin, sildenafil for pulmonary hypertension, and alfuzosin.

Serious adverse effects. Severe acute exacerbation of hepatitis B after stopping, lactic acidosis with hepatic steatosis (rare), kidney tubular injury (less than with the disoproxil salt), and immune reconstitution syndrome.

Common adverse effects. Diarrhoea, nausea, headache, fatigue and weight gain.

Interactions. - Cobicistat inhibits CYP3A4: avoid with many drugs, including the list of contraindications, and inhaled or injected corticosteroids (Cushing syndrome). - Polyvalent cations: separate antacids by at least 2 hours. - Do not combine with another booster or protease inhibitor.

Common prescribing errors. Using in pregnancy, giving with rifampicin, and missing cobicistat interactions.

Special groups. - Pregnancy: not advised because drug levels fall in the second and third trimesters. - Breastfeeding: limited data; avoid. - Children: tablet from 25 kg. - Older adults: usual dose with kidney checks. - Kidney impairment: avoid under CrCl 30 mL/min unless on dialysis. - Liver impairment: no adjustment in mild to moderate; not advised in severe.

Regional points. It is rarely available in East African public programmes, and rifampicin co-treatment excludes it.

Formulations. Fixed-dose tablet 150/150/200/10 mg.

Administration. Once daily with food.

Baseline. HIV test, hepatitis B status, creatinine and eGFR, urinalysis, drug history, pregnancy test.

Monitoring. Viral load at 6 months and then yearly; creatinine, phosphate and urinalysis yearly; interaction review at every prescription change.

Stopping thresholds. Stop only with hepatitis B cover; switch if pregnancy is confirmed.

Referral and escalation. Specialist review for pregnancy, virological failure and kidney decline.