Dolutegravir: A New Option for HIV Treatment

Alessia Carbone; Adriano Lazzarin; Antonella Castagna


Future Virology. 2014;9(9):801-810. 

In This Article

Abstract and Introduction


The need for new strategies for treating HIV-1 infection has led to the development of a number of new drugs. The aim of this article is to review the latest results of clinical trials of dolutegravir, an integrase inhibitor whose efficacy, tolerability and safety have been confirmed in treatment-naive and treatment-experienced patients. The findings, together with its high genetic barrier and limited interactions with other drugs, indicate that dolutegravir will play an important role in the future treatment of HIV infection.


Subjects with HIV-1 infection currently have a longer predicted lifespan and therefore need longer-term care.[1,2] The long-lasting success of HAART is often limited by drug toxicity, adherence to therapy and drug resistance,[3] thus making it necessary to increase the development of drugs that have a better pattern of resistance, adherence and tolerability and that do not interact with other drugs. Integrase inhibitors (INIs) make up one of the newest classes of drugs for the treatment of HIV infection.[4]

Integrase is one of the three viral enzymes that are essential for HIV-1 replication and, as it does not have a human homolog, it is an important target for treating HIV infection. It acts as a catalyst by inserting HIV DNA into the genome of the host cell with the mediation of the preintegration complex.[5]

Raltegravir (RAL), the first INI to become available in clinical practice, has been proved to be active in subjects who have developed resistance to other antiretroviral drugs. It has been tested in both treatment-naive and treatment-experienced patients, demonstrating good 5-year efficacy and safety data.[6,7] Nevertheless, this drug requires a twice-daily formulation,[8] and because of its relatively low genetic barrier,[9,10] failure on RAL-including regimens, which is often associated with resistance to this drug, is being increasingly observed in clinical practice.[11]

Elvitegravir (EVG) is another INI with well-documented 3-year efficacy and safety data in naive[12,13] and experienced patients.[14] It can be administered once daily and this represents a clear advantage in clinical practice. Nevertheless, EVG is not manufactured as a standalone agent, it needs a booster in order to maintain adequate plasma concentrations, there is a lack of published data concerning its use in children and, similarly to RAL, it shows a relatively low genetic barrier against resistance. Most of the mutations emerging during failure with EVG led to complete cross-resistance to RAL, thus preventing the sequential use of the two drugs.[15,16]

The emergence of INI resistance has been overcome, at least in part, by the discovery of the second-generation INI dolutegravir (DTG) as a result of the collaborative efforts of scientists working for Shionogi (Japan) and GlaxoSmithKline (UK).[17]