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Integrating Integrase Inhibitors Into an Antiretroviral Regimen

  • HIV Medicine (CJ Yoon, Section Editor)
  • Published:
Current Treatment Options in Infectious Diseases Aims and scope Submit manuscript

Opinion statement

Integrase strand transfer inhibitors (INSTI) are the newest drug class for treating HIV-1 infections and arguably the most important class available to clinicians. The INSTIs raltegravir, elvitegravir and dolutegravir block strand transfer, the final step catalyzed by integrase, thus preventing incorporation of the viral cDNA into the host genome and subsequent replication. INSTIs are potent, safe and extremely well tolerated. They are the only class of antiretroviral medications in which all members are now recommended by the United States Department of Health and Human Services (DHHS) as preferred first line therapy for treatment-naive HIV-infected patients. They provide a potent component in treatment-experienced patients who have failed prior therapy. INSTIs have minimal effect on serum lipids or glucose. Raltegravir and dolutegravir have few drug interactions, but elvitegravir is co-formulated with the CYP3A4 inhibitor cobicistat, which has significant drug interactions. Stewardship of the INSTI class is a prominent consideration for clinicians as resistance can develop even at low viral loads and mutations can confer cross-resistance within the class. Patients with virologic failure will continue to accumulate integrase resistance mutations over-time, therefore INSTIs should be stopped if virologic failure occurs to conserve sensitivity to other drugs in the class. Dolutegravir has a somewhat unique resistance pattern and appears to have a higher barrier to resistance, which may make it an option for patients who have failed prior raltegravir or elvitegravir-containing regimens. Treatment failure rates are more common in virologically suppressed patients with archived resistance. In patients with a history of virologic failure, switching from a boosted protease inhibitor to raltegravir is not recommended. Clinical trials are evaluating the compound GSK744, an analogue of dolutegravir with a long half-life, which may provide the option of administering INSTI-based antiretroviral therapy with long lasting depot injections rather than daily pills.

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Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

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Conflict of Interest

Philip M. Grant has received research support from Gilead Sciences and Viiv Healthcare.

Andrew R. Zolopa has received research support from Gilead Sciences, Pfizer, Janssen Therapeutics and Viiv Healthcare and is a paid consultant for Tibotec, Bristol-Myers Squibb, Janssen Therapeutics, and Gilead Sciences.

Sean E. Collins and Eugene T. Richardson report no conflicts of interest.

Human and Animal Rights and Informed Consent

This article references studies with human subjects performed by the authors. All studies were approved by the institutional review boards of the participating institutions, complied with the Helsinki Declaration and all study participants signed written informed consent.

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  1. Stanford University Division of Infectious Diseases and Geographic Medicine, 300 Pasteur Drive, L-134, Stanford, CA, 94305-5107, USA

    Sean E. Collins MD, Philip M. Grant MD, Eugene T. Richardson MD & Andrew R. Zolopa MD

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Collins, S.E., Grant, P.M., Richardson, E.T. et al. Integrating Integrase Inhibitors Into an Antiretroviral Regimen. Curr Treat Options Infect Dis 6, 144–158 (2014). https://doi.org/10.1007/s40506-013-0009-6

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