Dolutegravir: A New Integrase Strand Transfer Inhibitor for the Treatment of HIV

• Published in: Pharmacotherapy 2014-05, Vol.34 (5), p.506-520
• Main Authors: Shah, Bhavik M., Schafer, Jason J., DeSimone Jr, Joseph A.
• Format: Article
• Language: English
• Subjects: Biological and medical sciences; Clinical Trials as Topic; dolutegravir; Drug Interactions; Drug therapy; DTG; elvitegravir; Heterocyclic Compounds, 3-Ring - administration & dosage; Heterocyclic Compounds, 3-Ring - adverse effects; Heterocyclic Compounds, 3-Ring - pharmacokinetics; Heterocyclic Compounds, 3-Ring - therapeutic use; HIV; HIV Infections - drug therapy; HIV Infections - virology; HIV Integrase - metabolism; HIV Integrase Inhibitors - administration & dosage; HIV Integrase Inhibitors - adverse effects; HIV Integrase Inhibitors - pharmacokinetics; HIV Integrase Inhibitors - therapeutic use; Human immunodeficiency virus; Human viral diseases; Humans; Immunodeficiencies; Immunodeficiencies. Immunoglobulinopathies; Immunopathology; Infectious diseases; INSTI; integrase inhibitor; integrase strand transfer inhibitor; Medical sciences; Pharmacology. Drug treatments; raltegravir; S/GSK1349572; Treatment Outcome; Viral diseases; Viral diseases of the lymphoid tissue and the blood. Aids
• ISSN: 0277-0008; 1875-9114
• DOI: 10.1002/phar.1386

The first two integrase strand transfer inhibitors (INSTIs) approved for treatment of patients infected with human immunodeficiency virus (HIV) were raltegravir and elvitegravir. Both raltegravir and elvitegravir are now guideline‐preferred agents as part of an antiretroviral regimen for treatment‐naive patients. However, raltegravir is dosed twice/day. Elvitegravir is available in a single‐tablet regimen and dosed once/day because it is administered with the pharmacokinetic booster cobicistat, a potent CYP3A4 inhibitor that can lead to clinically significant drug–drug interactions. In addition, raltegravir and elvitegravir have a low genetic barrier to resistance and are associated with cross‐resistance. Dolutegravir is a new‐generation INSTI administered once/day without a pharmacokinetic booster and can be coformulated in a single‐tablet regimen. Phase III studies have demonstrated the efficacy and safety of dolutegravir for treatment‐naive and treatment‐experienced patients. Compared with other INSTIs, dolutegravir has a higher genetic barrier to resistance. Dolutegravir was approved by the U.S. Food and Drug Administration in August 2013 and joins raltegravir and elvitegravir as guideline‐preferred agents for the management for HIV‐infected treatment‐naive patients.