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Antiviral activity of HIV‐1 integrase strand‐transfer inhibitors against mutants with integrase resistance‐associated mutations and their frequency in treatment‐naïve individuals
Author(s) -
Margot Nicolas A.,
Ram Renee R.,
White Kirsten L.,
Abram Michael E.,
Callebaut Christian
Publication year - 2019
Publication title -
journal of medical virology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.782
H-Index - 121
eISSN - 1096-9071
pISSN - 0146-6615
DOI - 10.1002/jmv.25564
Subject(s) - integrase , dolutegravir , elvitegravir , virology , mutant , mutation , integrase inhibitor , resistance mutation , human immunodeficiency virus (hiv) , genetics , biology , antiretroviral therapy , gene , reverse transcriptase , viral load , rna
The development of resistance to human immunodeficiency virus 1 (HIV‐1) integrase strand‐transfer inhibitors (INSTI) has been documented; however, knowledge of the impact of pre‐existing integrase (IN) mutations on INSTI resistance (INSTI‐R) is still evolving. The frequency of HIV‐1 IN mutations in 2177 treatment‐naïve subjects was investigated, along with the INSTI susceptibility of site‐directed mutant viruses containing major and minor INSTI‐R mutations. Total 6 of 39 minor INSTI‐R mutations (M50I, S119P/G/T/R, and E157Q) were found in >1% of IN‐treatment‐naïve subjects with no impact on INSTI susceptibility. When each combined with major INSTI‐R mutation, M50I, S119P, and E157Q led to decreased susceptibility to elvitegravir but remained sensitive to dolutegravir and bictegravir.