LAUSR

Early initiation of antiretroviral therapy (ART) alters viral rebound kinetics after analytic treatment interruption (ATI) and may play a role in promoting HIV-1 remission. Autologous neutralizing antibodies (aNAbs) represent a key adaptive immune response in people living with HIV-1. We aimed to investigate the role of aNAbs in shaping post-ATI HIV-1 rebound variants. We performed single-genome amplification of HIV-1 env from pre-ART and post-ATI plasma samples of 12 individuals who initiated ART early after infection. aNAb activity was quantified using pseudoviruses derived from the most common plasma variant, and the serum dilution that inhibited 50% of viral infections was determined. aNAb responses matured while participants were on suppressive ART, because on-ART plasma and purified immunoglobulin G (IgG) demonstrated improved neutralizing activity against pre-ART HIV-1 strains when compared with pre-ART plasma or purified IgG. Post-ATI aNAb responses exerted selective pressure on the rebounding viruses, because the post-ATI HIV-1 strains were more resistant to post-ATI plasma neutralization compared with the pre-ART virus. Several pre-ATI features distinguished post-treatment controllers from noncontrollers, including an infecting HIV-1 sequence that was more similar to consensus HIV-1 subtype B, more restricted proviral diversity, and a stronger aNAb response. Post-treatment control was also associated with the evolution of distinct N-glycosylation profiles in the HIV-1 envelope. In summary, aNAb responses appeared to mature after early initiation of ART and applied selective pressure on rebounding viruses. The combination of aNAb activity with select HIV-1 sequence and reservoir features identified individuals with a greater chance of post-treatment control. Description Autologous neutralizing antibodies select for rebounding HIV-1 variants and may identify individuals with a greater chance of post-treatment control. ARTsy antibodies Post-treatment controllers (PTCs) are able to durably suppress human immunodeficiency virus (HIV)-1 after stopping antitretroviral therapy (ART). However, the features that distinguish PTCs from non-controllers (NC) remain unclear. Here, Esmaeilzadeh et al. evaluated plasma samples from six PTCs and six NCs who started ART early after infection, measuring viral load, viral diversity, and HIV-1 neutralizing antibody titers. The authors found that autologous neutralizing antibodies matured during antiretroviral therapy and was an important contributor to viral suppression after ART discontinuation. PTCs could be distinguished from NCs by a stronger neutralizing antibody response and a less diverse proviral reservoir. These features may be used to identify PTCs, although the authors highlight the need to look at a more diverse pool of individuals living with HIV-1. —CM