Two cases of dolutegravir failure with R263K mutation
نویسندگان
چکیده
منابع مشابه
Dolutegravir resistance mutation R263K cannot coexist in combination with many classical integrase inhibitor resistance substitutions.
The new integrase strand transfer inhibitor (INSTI) dolutegravir (DTG) displays limited cross-resistance with older drugs of this class and selects for the R263K substitution in treatment-experienced patients. We performed tissue culture selections with DTG, using viruses resistant to older INSTIs and infectivity and resistance assays, and showed that the presence of the E92Q or N155H substitut...
متن کاملThe R263K mutation in HIV integrase that is selected by dolutegravir may actually prevent clinically relevant resistance to this compound
INTRODUCTION Drug resistance against dolutegravir (DTG) or the nucleosides with which it has been co-administered has never been observed in patients receiving this drug in first-line therapy. In contrast, a R263K mutation that confers low-level resistance (3-4 fold) to DTG has been selected by DTG in culture. Our group has ascribed the absence of resistance to DTG to the high fitness cost exac...
متن کاملAddition of E138K to R263K in HIV integrase increases resistance to dolutegravir, but fails to restore activity of the HIV integrase enzyme and viral replication capacity.
BACKGROUND The results of several clinical trials suggest that the integrase inhibitor dolutegravir may be less prone than other drugs to the emergence of HIV drug resistance mutations in treatment-naive patients. We have shown that the R263K mutation commonly emerged during tissue culture selection studies with dolutegravir and conferred low levels of resistance to this drug while simultaneous...
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...
متن کاملThe R263K Dolutegravir Resistance-Associated Substitution Progressively Decreases HIV-1 Integration
Human immunodeficiency virus (HIV) infection persists despite decades of active antiretroviral therapy (ART), effectively preventing viral eradication. Treatment decreases plasma viral RNA, but viral DNA persists, mostly integrated within the genome of nucleated blood cells. Viral DNA blood levels correlate with comorbidities and the rapidity of viral rebound following treatment interruption. T...
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ژورنال
عنوان ژورنال: AIDS
سال: 2018
ISSN: 0269-9370
DOI: 10.1097/qad.0000000000001978