Resistance against Integrase Strand Transfer Inhibitors and Relevance to HIV Persistence

Autor: Thibault Mesplède, Mark A. Wainberg
Jazyk: angličtina
Rok vydání: 2015
Předmět:
Zdroj: Viruses, Vol 7, Iss 7, Pp 3703-3718 (2015)
Druh dokumentu: article
ISSN: 1999-4915
DOI: 10.3390/v7072790
Popis: 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.
Databáze: Directory of Open Access Journals