Humoral immunity to HIV-1: kinetics of antibody responses in chronic infection reflects capacity of immune system to improve viral set point

We analyzed the humoral immune response in 46 patients following structured treatment interruption (STI) to investigate the general potential of therapeutic vaccination in chronic HIV-1 infection. Evoked antibody titer increases to glycoprotein 120 (gp120) and p24 were low during 4 short-term STIs and only reached significance during a fifth long-term interruption. Although induction of binding antibodies to viral antigens was not associated with potent suppression of viremia, we observed that individuals with a rapid and high response to p24, and to a lesser extent also to gp120, lowered their viral set points significantly. Of note, the increase of the anti-p24 response correlated with specific CD4 T helper frequency to this antigen. Despite induction of binding antibody responses, which correlated with improved viral control, the increase in neutralizing activity was marginal and did not lead to this enhanced viral suppression. However, a subgroup of patients who potently suppressed viremia independently of STI had significantly higher pre-existing neutralization titers, suggesting a role of humoral immunity in conferring potent protection. In summary, measuring the kinetics of antibody responses provided a marker to validate the responsiveness and capacities of the immune system of HIV-1-infected individuals and reflected the patients' ability to decrease viral set points