Antiviral activity of HIV-1 integrase strand-transfer inhibitors against mutants with integrase resistance-associated mutations and their frequency in treatment-naïve individuals

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.人类免疫缺陷病毒1型（HIV-1）对整合酶链转移抑制剂（integrase strand-transfer inhibitors, INSTI）的耐药性演化已有文献报道，但学界对预先存在的整合酶（integrase, IN）突变对整合酶链转移抑制剂耐药性（INSTI-R）的影响认知仍在逐步完善。本研究调查了2177例HIV-1初治受试者体内的整合酶突变发生频率，并检测了携带主要及次要INSTI耐药突变的定点突变病毒对INSTI的敏感性。在39种次要INSTI耐药突变中，共有6种（M50I、S119P/G/T/R及E157Q）在超过1%的未接受过整合酶治疗的初治受试者中被检出，且上述突变对INSTI敏感性无显著影响。当上述次要突变与主要INSTI耐药突变联合存在时，M50I、S119P及E157Q会导致病毒对埃替格韦（elvitegravir）的敏感性下降，但仍对多替拉韦（dolutegravir）与比克替拉韦（bictegravir）保持敏感。