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What if HIV were unable to develop resistance against a new therapeutic agent?

Mark A Wainberg1*, Thibault Mesplède2 and Francois Raffi3

Author Affiliations

1 Departments of Medicine and Microbiology, Jewish General Hospital, McGill University, Montreal, QC, Canada

2 McGill University AIDS Centre, Montreal, QC, Canada

3 Division of Infectious Diseases, Nantes University Hospital, Nantes, France

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BMC Medicine 2013, 11:249  doi:10.1186/1741-7015-11-249

Published: 22 November 2013



The HIV integrase inhibitor, Dolutegravir (DTG), was recently approved by the Food and Drug Administration in the United States and is the only HIV drug that has not selected for resistance mutations in the clinic when used as part of first-line therapy. This has led to speculation that DTG might have a higher genetic barrier for the development of drug resistance than the other compounds that are used in therapy.


In this Opinion article, we speculate that this is due to greatly diminished replication capacity on the part of viruses that might become resistant to DTG when the drug is used in initial therapy and that DTG might be able to be used in HIV prevention and eradication strategies. We also note that no compensatory mutation that might restore viral replication fitness to HIV in the aftermath of the appearance of a single drug resistance mutation has yet to be observed.


DTG is a valuable addition to the anti-HIV armamentarium of drugs and its long-term utility may potentially exceed its obvious use in treatment of HIV disease.

Human immunodeficiency virus type 1; Integrase inhibitors; Antiretroviral therapy; Dolutegravir; HIV prevention strategies; Viral fitness; Drug resistance