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Mutations present in 15% of patients tested for InSTI resistance
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Among patients who underwent integrase genotypic resistance tests, approximately one of six demonstrated significant resistance to the first-generation integrase strand transfer inhibitors, researchers reported in Clinical Infectious Diseases.
Among the patients with resistance to elvitegravir or raltegravir (Isentress, Merck), 12% also demonstrated high-level resistance to dolutegravir (Tivicay, Viiv Healthcare), a second-generation integrase strand transfer inhibitor (InSTI).
“Although many providers had hoped that the new second-generation InSTI, dolutegravir, would be completely impervious to resistance mutations when their patients were failing raltegravir, that isn’t the case,” Christopher Hurt, MD, clinical assistant professor in the division of infectious diseases at the University of North Carolina at Chapel Hill, told Infectious Disease News. “These data highlight that although dolutegravir is an important addition to our treatment regiments, it isn’t invincible.”
Christopher Hurt
Hurt and colleagues compiled data on integrase sequences and demographics, which were paired with protease-reverse transcriptase genotypic resistance test results if available. They assessed for major mutations, including T66AIK, E92QV, F121Y, Y143CHR, S147G, Q148HKR and N155H. The analysis included 3,294 sequences from 3,012 patients, obtained from 2009 to 2012.
Among the patients in the analysis, 471 (15.6%) had at least one raltegravir or elvitegravir resistance mutations. The most common were the Q148 and N155 pathways, both of which were present in 197 patients. Another 84 patients had Y143 mutations. There were 224 patients with serial integrase genotypic resistance tests, and among these, 22 who had baseline wild-type acquired a major mutation.
“We hope that these data increase awareness of the importance of using integrase resistance testing to help manage patients on these medications who might be failing virologically,” Hurt said.
Hurt said it is assumed that most of the patients in this study developed resistance from exposure to raltegravir because elvitegravir became clinically available about 4 months before the study ended. He and colleagues aim to evaluate the data longitudinally to see what effect elvitegravir and dolutegravir have on patterns of resistance mutations.
“We also hope that our data will encourage surveillance for transmitted resistance, which is a blind spot for us, given the current guidelines that recommend only protease and reverse transcriptase genotyping at entry to care,” Hurt said.
Christopher Hurt, MD, can be reached at churt@med.unc.edu.
Disclosure: Hurt reports no relevant financial disclosures. Other researchers report research funding and/or consultancies with Bristol-Myers Squibb, Gilead, GlaxoSmithKline, Janssen, Merck and ViiV.
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