Table 1.
Drug | Raltegravir | Elvitegravir | Dolutegravir | GSK1265744LA |
---|---|---|---|---|
Manufacturer | Merck & Co | Gilead Sciences | ViiV & GSK | ViiV |
Generation | First | First | Second | Second |
FDA approved | 2007 | 2012 | 2013 | N/A |
Tolerability | Good | Good | Good | N/A |
Food requirement | No | Yes | No | No |
Metabolism | UGT1A1 | Cytochrome P450 CYP3A4 major; UGT1A1/3 minor |
Glucuronidation UGT1A1 major; CYP3A4 minor |
|
Half-life: t 1/2 | 9 h | 3 h alone; 9 h with cobicistat boost | 12–15 h (average 14 h) | 21–50 days (nanosuspension) |
Renal/biliary | Competitive use of UGT1A1a to metabolize drug and unconjugated bilirubin | Inhibitor of OCT2b, inhibiting creatinine secretion, no effect on GFR; small rise in bilirubina | ||
Adult dosing | 400 mg twice daily | Daily combination pill | 50 mg daily in INSTI-naïve; 50 mg twice daily in INSTI-experienced |
Treatment: 600-mg bimonthly injection (under investigation) PrEP: 800-mg quarterly injection (under investigation) |
Pediatric dosing | Chewable tabs 100 and 25 mg | Not available | 50 mg once daily in 12 years and older and weighing at least 40 kg; pediatric granule formulation in process | Not available |
Co-treatment for tuberculosis | Rifampin: decreases AUC, induces UGT1A1, increase dose by 100%; rifabutin: no dose adjustment | Avoid with rifabutin due to drug/drug interactions | Rifampin: dose adjust 50 mg twice daily; rifabutin: no need to dose adjust | |
Cross-resistant | Yes | Yes | No; exception may be Q148 + ≥2 additional mutations | No |
AUC area under curve, GFR glomerular filtration rate, GSK GlaxoSmithKline, INSTI integrase strand transfer inhibitor, PrEP pre-exposure prophylaxis, t 1/2 half-life
aUGT1A1 is the same metabolic enzyme that processes unconjugated bilirubin setting up a competitive use
bHuman organic cation transporter