The role of dolutegravir in the management of HIV infection

• Published in: Infection and drug resistance Vol. 8; pp. 19 - 29
• Main Authors: Miller, Misty M, Liedtke, Michelle D, Lockhart, Staci M, Rathbun, R Chris
• Format: Journal Article
• Language: English
• Published: New Zealand Dove Medical Press Limited 01-01-2015; Dove Medical Press
• Subjects: Drug therapy; HIV infection; Review; antiretroviral; Tivicay; treatment-experienced studies; treatment-naïve studies; integrase inhibitor
• ISSN: 1178-6973; 1178-6973
• DOI: 10.2147/IDR.S58706

Dolutegravir is the most recent integrase strand transfer inhibitor approved for HIV-1 infection in both treatment-naïve and experienced patients. As a tricyclic carbamoyl pyridone analog, dolutegravir is rapidly absorbed and distributes through the cerebrospinal fluid. It is hepatically metabolized by uridine diphosphate glucuronosyl transferase 1A1; no inhibition or induction of cytochrome P450 enzymes is noted. As a substrate of CYP 3A4, dolutegravir is affected by rifampin, efavirenz, tipranavir/ritonavir, fosamprenavir/ritonavir, and dose increase is required. Dolutegravir inhibits the organic cation transporter 2, resulting in decreased creatinine clearance with no apparent decrease in renal function. Other adverse effects are minimal but include diarrhea, headache, and nausea. Clinical trials in treatment-naïve and experienced patients are ongoing and will be presented in this text.