Will drug resistance against dolutegravir in initial therapy ever occur?
نویسندگان
چکیده
Dolutegravir (DTG) is a second-generation integrase strand transfer inhibitor (INSTI) and INSTIs are the latest class of potent anti-HIV drugs. Compared to the first generation INSTIs, raltegravir, and elvitegravir, DTG shows a limited cross-resistance profile. More interestingly, clinical resistance mutations to DTG in treatment-naive patents have not been observed to this date. This review summarizes recent studies on resistance mutations to DTG and on our understanding of the mechanisms of resistance to DTG as well as future directions for research.
منابع مشابه
Integrase Strand Transfer Inhibitors in HIV Therapy
HIV drug resistance has been one of the major obstacles to HIV eradication and has contributed to the need for the constant development of new antiretroviral drugs over the past 25 years. With the recent approval of dolutegravir for human therapy by the U.S. Food and Drug Administration, health practitioners may soon have access to three integrase strand transfer inhibitors to treat individuals...
متن کاملWhat if HIV were unable to develop resistance against a new therapeutic agent?
BACKGROUND 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 comp...
متن کاملImplications for the future of the HIV epidemic if drug resistance against dolutegravir cannot occur in first-line therapy
Received 3 November 2015; Revised 19 November 2015; Accepted 19 November 2015; Published 4 December 2015 Copyright: – 2015 Wainberg MA and Mesplede T; licensee International AIDS Society. This is an Open Access article distributed under the terms of the Creative Commons Attribution 3.0 Unported (CC BY 3.0) License (http://creativecommons.org/licenses/by/3.0/), which permits unrestricted use, di...
متن کاملThe Combination of the R263K and T66I Resistance Substitutions in HIV-1 Integrase Is Incompatible with High-Level Viral Replication and the Development of High-Level Drug Resistance.
UNLABELLED The R263K substitution in integrase has been selected in tissue culture with dolutegravir (DTG) and has been reported for several treatment-experienced individuals receiving DTG as part of salvage therapy. The R263K substitution seems to be incompatible with the presence of common resistance mutations associated with raltegravir (RAL), a different integrase strand transfer inhibitor ...
متن کاملResistance mutations against dolutegravir in HIV integrase impair the emergence of resistance against reverse transcriptase inhibitors.
OBJECTIVE Among 1222 antiretroviral-naive patients who received dolutegravir (DTG) as part of first-line therapy, none has developed resistance against this compound after 48-96 weeks of follow-up. Moreover, only four occurrences of virological failure with resistance mutations have been documented in previously drug-experienced patients who received DTG as a first time integrase inhibitor as a...
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