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Clinical trials of HIV antiretroviral therapy: Integrase inhibitors

Paul E Sax, MD
Section Editor
John G Bartlett, MD
Deputy Editor
Jennifer Mitty, MD, MPH


HIV-1 integrase is essential for viral replication; integrase inserts viral DNA into the cellular genome through two catalytic reactions. Loss of integrase activity disrupts the viral life cycle. Inhibitors of the integrase function have potent in vitro and in vivo antiviral activity.

This topic will discuss clinical trials data on the three integrase inhibitors available for clinical use: raltegravir, the first agent available in this class, elvitegravir, which is available in a co-formulated tablet in combination with cobicistat, tenofovir, and emtricitabine, and dolutegravir, which is approved for use in combination with abacavir/lamivudine and tenofovir/emtricitabine for individuals who are antiretroviral naïve, and is active in patients with multidrug HIV resistance. 

The pharmacology of integrase inhibitors, as well as the indications for initiating antiretroviral therapy (ART) and the selection and monitoring of these regimens, is discussed elsewhere. (See "Patient monitoring during HIV antiretroviral therapy" and "Selecting antiretroviral regimens for the treatment-naïve HIV-infected patient" and "When to initiate antiretroviral therapy in HIV-infected patients" and "Considerations prior to initiating antiretroviral therapy" and "Selecting an antiretroviral regimen for treatment-experienced HIV-infected patients who are failing therapy" and "Overview of antiretroviral agents used to treat HIV".)


Raltegravir (MK-0518) is an integrase inhibitor with potent in vitro activity against both wild-type and multidrug-resistant HIV [1]. It is metabolized by hepatic glucuronidation and has no effect on cytochrome 3A4 [2]. Raltegravir is used for the treatment of antiretroviral naïve and experienced individuals. The risk of resistance is lower when coadministered with other active agents; when resistance occurs, it is associated with the emergence of mutations at several potential sites, most commonly Q148R or N155H. The clinical trials that support these recommendations are described below.

Treatment-naive patients — Raltegravir has demonstrated significant efficacy in treatment-naive patients. Studies show that raltegravir has rapid, potent, and durable efficacy with a lower rate of adverse events than efavirenz [3-5]. In treatment-naïve patients, raltegravir should be given twice daily.


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Literature review current through: Sep 2016. | This topic last updated: Oct 3, 2013.
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