Transient viral exposure drives functionally-coordinated humoral immune responses in HIV-1 post-treatment controllers

A rare sub-population of people living with HIV-1 experience long-lasting viral remission after interrupting antiretroviral therapy and are considered post-treatment controllers. Here the authors characterise the humoral immune response to HIV-1 in a cohort of post-treatment controllers. HIV-1 post-treatment controllers are rare individuals controlling HIV-1 infection for years after antiretroviral therapy interruption. Identification of immune correlates of control in post-treatment controllers could aid in designing effective HIV-1 vaccine and remission strategies. Here, we perform comprehensive immunoprofiling of the humoral response to HIV-1 in long-term post-treatment controllers. Global multivariate analyses combining clinico-virological and humoral immune data reveal distinct profiles in post-treatment controllers experiencing transient viremic episodes off therapy compared to those stably aviremic. Virally-exposed post-treatment controllers display stronger HIV-1 humoral responses, and develop more frequently Env-specific memory B cells and cross-neutralizing antibodies. Both are linked to short viremic exposures, which are also accompanied by an increase in blood atypical memory B cells and activated subsets of circulating follicular helper T cells. Still, most humoral immune variables only correlate with Th2-like circulating follicular helper T cells. Thus, post-treatment controllers form a heterogeneous group with two distinct viral behaviours and associated immune signatures. Post-treatment controllers stably aviremic present silent humoral profiles, while those virally-exposed develop functionally robust HIV-specific B-cell and antibody responses, which may participate in controlling infection.

Automated summary

This study characterized the humoral immune response to HIV-1 in post-treatment controllers and found that they can be divided into two distinct groups based on viral behavior and immune signatures. Virally-exposed post-treatment controllers displayed stronger immune responses, which may contribute to their ability to control infection.