New perinatal HIV infections continue, at a rate of about one every 4 minutes. Treatment with antiretroviral therapy (ART) limits the size of the persistent reservoir in children but also limits the development of antiviral immune responses. Upon interruption of ART, viral rebound occurs in the majority of cases even following very early treatment, indicating formation of the rebound-competent reservoir soon after infection. Children infected by breastfeeding typically have a more delayed diagnosis and thus do not receive very early ART. These children in particular may benefit from immunotherapies added to ART at the onset of their treatment course.
The experiments proposed here will provide new evidence regarding the mechanisms of HIV/SIV reservoir establishment and how this process may be perturbed in a model of perinatal infection. While several studies using bNAbs have been conducted or are in progress/proposed in newborns and children, none involve the addition of additional virus- and/or host-direct immunotherapies. Combination therapy may prove to be the next frontier in pediatric cure research; however, given unknowns regarding safety and efficacy, initial studies in a relevant pediatric nonhuman primate model are essential.