Characterization of HIV humoral immunity during analytical treatment interruption

This study investigated whether HIV binding antibody (Ab) and p24 antigen (Ag) quantitation could detect humoral immune responses or p24 Ag before or following detectable plasma viral load (VL) rebound during antiretroviral therapy interruption (ATI) and provide insights into post-rebound viral replication.

Longitudinal plasma samples collected before and following ATI from 40 participants (485 samples; mean of 12/participant) in the ACTG A5345 study who began antiretroviral therapy during either acute or chronic stages of infection were analyzed using commercial immunoassays to assess HIV Ab and Ag dynamics, including following dissociation of immune complexes for improved Ag detection.

Neither Ab nor Ag levels increased in plasma before VL rebound. However, 75% of participants exhibited increased Ab reactivity concurrent with or shortly after VL rebound, which declined upon ART reinitiation. Participants who were ART-treated early had lower Ab levels at ATI initiation but demonstrated greater fold increases in Ab during ATI than late-treated participants. Two participants who demonstrated post-treatment control of VL showed gradual Ab increases that paralleled intermittent VL elevations. p24 Ag was only detectable after dissociating immune complexes in samples with VL > 10⁴ RNA copies/mL, correlating strongly with VL levels.

Although antibody levels did not predict viral rebound, tracking their longitudinal changes provided meaningful information about viral replication patterns and immune reactivation during and after rebound, offering a practical tool for monitoring ATI outcomes.