In vitro comparison of the susceptibilities of the same drug resistance mutations to reverse-transcriptase inhibitors of subtype B and CRF01_AE HIV-1 strains

As the recommended drugs for first-line regimens in HIV-1 infections, reverse-transcriptase inhibitors (RTIs) are widely used around the world. To escape from the selective pressure imposed by RTIs, HIV-1 constantly mutates to adapt to its environment. However, it is unclear how resistance mutations emerging in response to RTIs affect drug susceptibility in strains of different subtypes. To explored this phenomenon, typical RTI-induced drug resistance mutations (DRMs) were selected to test their effects on the susceptibility of different subtype strains. The same RTI-induced DRMs were introduced into infectious clones of subtypes B and CRF01_AE, and phenotypic resistance tests were performed to compare the differences in susceptibilities to various RTIs. The experimental results revealed that mutations such as M41L and V106M were more likely to occur in the CRF01_AE subtype. However, phenotypic analysis of reconstructed clones containing these resistance mutations revealed that CRF01_AE exhibited significantly lower sensitivity to RTIs than did subtype B. For azvudine (FNC), a novel nucleoside reverse transcriptase inhibitor (NRTI), the resistance level of CRF01_AE was significantly lower than that of subtype B. In conclusion, the same mutation affecting resistance to RTIs can have significantly different impacts depending on the subtype of the HIV-1 strain. This finding serves as a reference for guiding rational drug use in the future. Moreover, relying solely on phenotypic experimental results from subtype B to evaluate resistance levels of unclear mutations in other subtypes may be inappropriate and should be approached with caution.