Table 1.

Comparison of currently available and future integrase inhibitors

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