Bictegravir

Bictegravir is an oral integrase strand transfer inhibitor available only in a single fixed-dose tablet with emtricitabine and tenofovir alafenamide. It has a high barrier to resistance and is used for first-line and switch therapy in adults and children. It has no booster, but strong enzyme inducers such as rifampicin lower its levels.

Class. Integrase strand transfer inhibitor.

Mechanism. Binds the integrase active site and blocks strand transfer. It keeps activity against most dolutegravir-naive resistance patterns.

Pharmacokinetics. Oral absorption not affected by food. Half life about 18 hours. Metabolised by CYP3A4 and UGT1A1. It inhibits OCT2 and MATE1, raising serum creatinine without true change in glomerular filtration.

HIV-1 infection (adults and children 25 kg or more). One tablet orally once daily containing bictegravir 50 mg, emtricitabine 200 mg and tenofovir alafenamide 25 mg.

Children 14 to under 25 kg. One tablet containing bictegravir 30 mg, emtricitabine 120 mg and tenofovir alafenamide 15 mg once daily.

Dose adjustment for kidney function. CrCl 30 mL/min or more: no adjustment; under 30 and not on dialysis: not advised; on haemodialysis: acceptable, given after dialysis.

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

Main alternative. Dolutegravir with tenofovir and lamivudine.

Contraindications. Hypersensitivity; co-administration with dofetilide or rifampicin.

Serious adverse effects. Severe acute exacerbation of hepatitis B after stopping, lactic acidosis with hepatic steatosis (rare), hepatotoxicity, and immune reconstitution syndrome.

Common adverse effects. Headache, diarrhoea, nausea, fatigue, weight gain and mild creatinine rise.

Interactions. - Rifampicin, rifapentine, carbamazepine, phenytoin, phenobarbital and St John’s wort: avoid. - Polyvalent cations: take 2 hours before antacids containing aluminium or magnesium; with food, calcium and iron can be taken together. - Metformin: raises levels; monitor.

Common prescribing errors. Giving with rifampicin, taking on an empty stomach with iron or calcium, and stopping in hepatitis B without cover.

Special groups. - Pregnancy: safe data are limited but increasing; dolutegravir has more. - Breastfeeding: limited data; avoid unless benefit is clear. - Children: lower-strength tablet from 14 kg. - Older adults: usual dose. - Kidney impairment: avoid under CrCl 30 mL/min unless on haemodialysis. - Liver impairment: no adjustment in mild to moderate; not advised in severe.

Regional points. It is little used in East African public programmes, where tuberculosis co-treatment with rifampicin is common and rules it out.

Formulations. Fixed-dose tablets 50/200/25 mg and 30/120/15 mg.

Administration. Once daily with or without food.

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

Monitoring. Viral load at 6 months and then yearly; creatinine, phosphate and urinalysis yearly; weight and lipids.

Stopping thresholds. Stop only with hepatitis B cover; stop for ALT over 3 times the upper limit of normal with symptoms, or over 5 times without.

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