Naturally occurring resistance mutations to HIV-1 entry inhibitors in subtypes B, C, and CRF31_BC

Abstract Background Entry inhibitors are a class of antiretroviral (ARV) drugs that prevent HIV replication by blocking viral entry into the host cell. The investigation of naturally occurring mutations associated with entry inhibitors across subtypes is required because genetic differences between HIV-1 variants may influence the emergence of drug resistance. Despite the importance of subtype C, which predominates globally, the majority of studies include only subtype B strains. Objectives To investigate the presence of natural resistance mutations to entry inhibitors in HIV-1 subtypes B, C, and CRF31_BC strains. Study design Eighty samples were collected from antiretroviral-naive patients. The gp41 gene from 67 patients and the gp120 gene from 65 patients were partially sequenced. Resistance mutations to entry inhibitors Enfuvirtide, Maraviroc, and Vicriviroc were screened. Results ENF resistance-associated mutations of HR1 and HR2 on gp41 were not associated with any subtype. However, the major polymorphisms detected in HR1: N42S, L54M, and A67T were most prevalent in subtype C ( p p Conclusions This study shows that many more resistance-associated mutations to entry inhibitors in ARV-naive patients occur in subtype C compared with subtype B strains. However, further studies will be necessary to elucidate if the differential genetic background of HIV subtypes can affect the efficacy of treatment with entry inhibitors.