Delayed viral rebound post-ART interruption in infant macaques given SIV-specific neutralizing antibodies

Interventions to prevent HIV rebound in the absence of antiretroviral therapy (ART) are needed. Here, we use a rhesus macaque model of pediatric HIV to assess the impact of simian immunodeficiency virus (SIV) Env-specific rhesus monoclonal antibodies (RhmAbs) on viral rebound. We find that RhmAb-treated infants experience delayed rebound compared to controls (median of 64 versus 7.5 days, p = 0.0007). Time to rebound very strongly correlates with both ITS102.01-LS concentrations (r = 0.9, p = 0.002) and anti-drug antibodies against ITS103.01-LS (r = -0.95, p = 0.008). SIVgag-specific CD8⁺ T cell levels increase after RhmAb administration and negatively correlate with rebound viremia (r = -0.67, p = 0.0415). Treatment also expands neutralization breadth and potency against tier 2 and tier 3 viruses in 5/8 and 3/8 RhmAb-receiving animals, respectively. Thus, giving SIV Env RhmAbs prior to ART cessation leads to prolonged time to viral rebound, enhanced antiviral T cell responses, and broadening of neutralization capacity, thereby supporting use of neutralizing Abs to promote post-ART viral control.