Escape from humoral immunity is associated with treatment failure in HIV-1-infected patients receiving long-term antiretroviral therapy

Interindividual heterogeneity in the disease progression of HIV-1-infected patients receiving long-term antiretroviral therapy suggests that some host-related factors may have limited treatment efficacy. To understand the nature of factors contributing to treatment failure, we performed a retrospective cohort study of 45 chronically HIV-1-infected individuals sharing a similar demographics and route of infection, compared the differences between virologically suppressed (VS) and treatment failure (TF) patients with respect to clinical, immunological and virological characteristics. We found that the baseline diversity of HIV-1 env quasispecies was the major difference between VS and TF group, and higher baseline diversity in TF patients. We further predicted TF-related env mutations using a selection pressure-based approach, followed by an analysis of these mutations based on the available three-dimensional structures of gp120/gp41 or their complexes with neutralizing antibodies. Notably, almost all of the identified residues could be mapped to the epitopes of known HIV-1 neutralizing antibodies, especially the epitopes of broadly neutralizing antibodies, and these mutations tended to compromise antibody-antigen interactions. These results indicate that the escape of HIV-1 from host humoral immunity may play a direct role in TF in long-term antiretroviral-experienced patients and that based on env gene sequence of the viruses in the patients.