Abstract Long-term viral suppression with antiretroviral treatment (ART) is difficult to maintain over the course of an entire lifetime, and significant toxicities to ART may accumulate with time. Novel strategies that maintain HIV viral suppression while allowing time off 3-drug ART are needed, and proof-of-concept studies to demonstrate the feasibility of such a strategy – and to study its impact on viral reservoir, immune responses, and clinical outcomes – are of high priority. We propose an open-label Phase 1/2 study to evaluate the efficacy of the broadly neutralizing HIV-1 monoclonal antibody VRC01 to maintain viral suppression in the absence of ART among virally suppressed HIV-infected children who started standard ART within 96 hours of birth (or soon after intrapartum infection). All children will be recruited from the Early Infant Treatment (EIT) study (U01AI114235), and have been followed from birth with frequent assessments of their clinical, virologic and immunologic characteristics. Children who have received 96-240 weeks of ART and meet virologic entry criteria will be offered enrollment into the proposed study. The intervention will consist of ongoing ART plus infusions of VRC01 antibodies for a period of 6 weeks, followed by monthly maintenance administration of VRC01 treatment alone for up to 24 additional weeks. Children receiving VRC01 maintenance therapy will be monitored closely, with immediate re-initiation of ART following any VL > 400 copies/mL. All participants will resume ART at week 30. The study is designed to evaluate three possible benefits of VCR01 therapy in HIV-1- infected children: 1) we will characterize the duration of virologic control that can be maintained with VRC01 treatment following early ART, providing proof-of-concept that VRC01 may serve as a possible alternative to standard ART in children with low viral reservoirs; 2) we will investigate whether VRC01 therapy is associated with changes in the size and/or the cellular or clonal composition of residual viral reservoirs, which will be highly informative for developing strategies to limit viral persistence and to destabilize viral reservoir homeostasis in pediatric patients; and 3) we will evaluate whether treatment with VRC01 is associated with qualitative or quantitative changes in innate or adaptive antiviral immune responses, and if it facilitates the development of an antiviral immune profile that can enable spontaneous post-treatment viral control.