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Review

Resistance against Integrase Strand Transfer Inhibitors and Relevance to HIV Persistence

1
McGill University AIDS Centre, Lady Davis Institute for Medical Research, Jewish General Hospital, Montréal, QC H3T 1E2, Canada
2
Division of Experimental Medicine, Faculty of Medicine, McGill University, Montréal, QC H3A 2R7, Canada
3
Department of Microbiology and Immunology, Faculty of Medicine, McGill University, Montréal, QC H3A 0G4, Canada
*
Authors to whom correspondence should be addressed.
Academic Editor: Eric O. Freed
Viruses 2015, 7(7), 3703-3718; https://doi.org/10.3390/v7072790
Received: 6 May 2015 / Revised: 29 June 2015 / Accepted: 2 July 2015 / Published: 7 July 2015
(This article belongs to the Special Issue Gene Technology and Resistance to Viruses - Reviews)
Drug resistance prevents the successful treatment of HIV-positive individuals by decreasing viral sensitivity to a drug or a class of drugs. In addition to transmitted resistant viruses, treatment-naïve individuals can be confronted with the problem of drug resistance through de novo emergence of such variants. Resistant viruses have been reported for every antiretroviral drug tested so far, including the integrase strand transfer inhibitors raltegravir, elvitegravir and dolutegravir. However, de novo resistant variants against dolutegravir have been found in treatment-experienced but not in treatment-naïve individuals, a characteristic that is unique amongst antiretroviral drugs. We review here the issue of drug resistance against integrase strand transfer inhibitors as well as both pre-clinical and clinical studies that have led to the identification of the R263K mutation in integrase as a signature resistance substitution for dolutegravir. We also discuss how the topic of drug resistance against integrase strand transfer inhibitors may have relevance in regard to the nature of the HIV reservoir and possible HIV curative strategies. View Full-Text
Keywords: HIV; integrase strand-transfer inhibitors; resistance; raltegravir; elvitegravir; dolutegravir; R263K; viral fitness; viral reservoirs; HIV eradication HIV; integrase strand-transfer inhibitors; resistance; raltegravir; elvitegravir; dolutegravir; R263K; viral fitness; viral reservoirs; HIV eradication
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MDPI and ACS Style

Mesplède, T.; Wainberg, M.A. Resistance against Integrase Strand Transfer Inhibitors and Relevance to HIV Persistence. Viruses 2015, 7, 3703-3718. https://doi.org/10.3390/v7072790

AMA Style

Mesplède T, Wainberg MA. Resistance against Integrase Strand Transfer Inhibitors and Relevance to HIV Persistence. Viruses. 2015; 7(7):3703-3718. https://doi.org/10.3390/v7072790

Chicago/Turabian Style

Mesplède, Thibault, and Mark A. Wainberg. 2015. "Resistance against Integrase Strand Transfer Inhibitors and Relevance to HIV Persistence" Viruses 7, no. 7: 3703-3718. https://doi.org/10.3390/v7072790

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