Dolutegravir: A New HIV Integrase Inhibitor for the Treatment of HIV Infection

Blake Max; Sonia Vibhakar


Future Virology. 2014;9(11):967-978. 

In This Article

Abstract and Introduction


Dolutegravir is a second-generation HIV integrase strand transfer inhibitor (INSTI) and the most recent antiretroviral approved for treatment of HIV-1 infection. Dolutegravir in combination with two nucleoside reverse transcriptase inhibitors is one of the preferred regimens recommended by the Department of Health and Human Services HIV treatment guidelines for treatment-naive adults and adolescents. This recommendation is based on clinical trial data where dolutegravir demonstrated superiority compared with guideline preferred regimens containing efavirenz and ritonavir-boosted darunavir and noninferiority compared with first-generation INSTI, raltegravir. Dolutegravir also demonstrated superiority when compared with raltegravir in treatment-experienced, integrase-naive patients and clinical efficacy in patients with resistance to first-generation INSTIs. Overall, dolutegravir has demonstrated excellent tolerability, limited drug interactions, minimal drug resistance and once-daily dosing for treatment-naive patients.


For almost two decades antiretroviral therapy has decreased morbidity and mortality for HIV infected patients.[1] Since the introduction of highly active antiretroviral therapy in 1996 medications to treat HIV have steadily improved. HIV clinicians now have at their disposal five distinct classes of antiretroviral medications, the most recent class that has had a major impact on the treatment of HIV infection are the HIV integrase strand transfer inhibitors (INSTIs). There are currently three US FDA approved INSTIs: raltegravir (Isentress®, Merck Sharp & Dohme Corp., NJ, USA), elvitegravir (available as a fixed dose combination tablet Stribild® [Stribild-Gilead Sciences, Inc., CA, USA] in the USA) and dolutegravir (Tivicay®, ViiV Healthcare, NC, USA). Dolutegravir, a second-generation INSTI, is the most recent FDA-approved antiretroviral that has demonstrated impressive antiviral efficacy based on randomized controlled trials compared with other first-line regimens recommended by the Department of Health and Human Services HIV treatment guidelines for adults and adolescents.[2] Dolutegravir has excellent pharmacokinetic characteristics, is well tolerated, has few drug interactions, minimal drug resistance and can be dosed once or twice daily depending on prior HIV integrase resistance. In August 2013, dolutegravir was FDA approved for treatment of HIV-1 infected patients over the age of 12 years and weighing over 40 kg. This article reviews the pharmacology, pharmacokinetics, clinical efficacy, resistance, safety and drug interactions of dolutegravir.