Identification of HIV Mutations in Donors Experiencing Virologic Failure on Raltegravir-Containing Regimens

Abstract

HIV still remains a public global health concern with 38 million people living with HIV. There is no cure to HIV, however combination antiretroviral therapy (ART) is a highly effective treatment that suppresses the virus. Despite the effectiveness of ART, drug resistance mutations can arise, typically found in the target gene. However, previous in vitro studies have identified drug resistance mutations to integrase inhibitors in non-target genes. In this study, we investigated whether mutations in non-target genes, gag Nucleocapsid (NC) and/or nef (3’PPT) might also contribute to drug resistance and virologic failure in five individuals with HIV failing Raltegravir (an integrase inhibitor). Single- Genome Sequencing (SGS) was performed on plasma-derived viruses from pre-ART and early and/or late ART failure samples from these participants, then the gag and nef sequences were analyzed for mutations. We specifically identified a mutation, V24I, in the Nucleocapsid region of gag in vivo that is similar to previously identified resistance mutations in vitro. This analysis suggests that non-target genes may contribute to the emergence of drug resistance in vivo.