Differential Sensitivities of Retroviruses to Integrase Strand Transfer Inhibitors
نویسندگان
چکیده
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 کاملStructure-Guided Optimization of HIV Integrase Strand Transfer Inhibitors
Integrase mutations can reduce the effectiveness of the first-generation FDA-approved integrase strand transfer inhibitors (INSTIs), raltegravir (RAL) and elvitegravir (EVG). The second-generation agent, dolutegravir (DTG), has enjoyed considerable clinical success; however, resistance-causing mutations that diminish the efficacy of DTG have appeared. Our current findings support and extend the...
متن کاملMutations Located outside the Integrase Gene Can Confer Resistance to HIV-1 Integrase Strand Transfer Inhibitors
Resistance to the integrase strand transfer inhibitors raltegravir and elvitegravir is often due to well-identified mutations in the integrase gene. However, the situation is less clear for patients who fail dolutegravir treatment. Furthermore, most in vitro experiments to select resistance to dolutegravir have resulted in few mutations of the integrase gene. We performed an in vitro dolutegrav...
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HIV integrase (IN) strand transfer inhibitors (INSTIs) are among the newest anti-AIDS drugs; however, mutant forms of IN can confer resistance. We developed noncytotoxic naphthyridine-containing INSTIs that retain low nanomolar IC50 values against HIV-1 variants harboring all of the major INSTI-resistant mutations. We found by analyzing crystal structures of inhibitors bound to the IN from the ...
متن کاملTransmitted resistance to HIV integrase strand-transfer inhibitors: right on schedule.
Transmitted drug resistance (TDR), the primary acquisition of an HIV variant already resistant to antiretrovirals, affects approximately 15% of all new infections in the United States. Historically, from the time initial agents in the reverse transcriptase, protease and entry inhibitor classes were introduced, it took 3-5 years before the first case reports of TDR appeared. With the description...
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ژورنال
عنوان ژورنال: Journal of Virology
سال: 2011
ISSN: 0022-538X,1098-5514
DOI: 10.1128/jvi.02541-10