The purpose of this study was to evaluate the safety and antiviral activity to promote clearance of HIV-1 infected cells of VRC01 in infants with HIV beginning combination antiretroviral therapy (cART).

VRC01 is an experimental human immunoglobulin G1 (IgG1) monoclonal antibody. The purpose of this study was to evaluate the safety and antiviral activity to promote clearance of HIV-1 infected cells of VRC01 received within 12 weeks of birth in infants with HIV initiating cART.

All infants were required to have initiated cART within 14 days before or at study entry. Infants were randomly assigned to either receive VRC01 (VRC01, Arm 1) or not receive VRC01 (No-VRC01, Arm 2). Randomization was stratified by whether the initial cART regimen included an integrase inhibitor.

Infants in the VRC01 arm received VRC01 injections at study entry (Week 0) and Weeks 2, 6, and 10. Infants in the No-VRC01 arm received no study product.

Infants attended study visits at Weeks 1, 2, 3, 6, 7, 10, 11, 14, 16, 20, 24, 36, and 48. Visits included physical examinations, blood and urine collection.

Infants' mothers could optionally be enrolled in the study for one-time specimen collection for exploratory evaluations. Maternal study participation was not required for infant study participation.

The study was closed to enrollment prematurely on March 19, 2020 due to the outbreak of coronavirus disease 2019 (COVID-19) and after enrolling 61 of the targeted 68 infants.

Infant Inclusion Criteria:

• Weigh at least 2500 grams

• Confirmed HIV-1 infection

• The following laboratory values at screening:

  • Cluster of differentiation 4 (CD4) lymphocyte percentage greater than 15
  • Severity grade 1 or lower hemoglobin, platelet count, and absolute neutrophil count
  • Severity grade 1 or lower alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase

• First dose of initial combination antiretroviral therapy (cART) regimen taken on the day of randomization or within 14 days prior to the day of randomization

• Expected to be available for 48 weeks of follow-up at study entry

• Parent or legal guardian willing and able to provide written informed consent for infant participation in the study

• Parent or legal guardian willing and able to complete reactogenicity memory aids for study purposes, based on parent/guardian report.

Infant Exclusion Criteria:

• Infant or infant's mother received exclusionary active or passive HIV-specific immunotherapy

• Initiated a combination of three or more antiretrovirals, all at or above recommended treatment doses, within 48 hours of birth

• Received within 30 days prior to study entry, or was identified as requiring, any of the following:

  • Chronic (more than 14 days) systemic steroid treatment
  • Immunoglobulin treatment
  • Immunomodulators (interleukins, interferons, cyclosporin)
  • Cytotoxic chemotherapy
  • Treatment for active tuberculosis (TB) disease
  • Any investigational agent
  • Note: Treatment for latent TB infection was permitted

• Any documented or suspected clinically significant medical illness, clinically significant congenital anomaly, or immediately life-threatening condition that, in the opinion of the site investigator or designee, would interfere with the infant's ability to comply with study requirements

• Any other condition that, in the opinion of the site investigator or designee, would make participation in the study unsafe, complicate interpretation of study outcome data, or otherwise interfere with achieving the study objectives

Maternal Inclusion Criteria (maternal study participation was not required for infant study participation):

The mothers of enrolled infants were asked to consent to blood collection and storage for this study. The following criteria must have been met in order for mothers to undergo blood collection for this purpose:

• Mother was willing and able to provide independent written informed consent for blood collection and storage for virology and immunology investigations
• Mother had no documented or suspected condition that, in the opinion of the site investigator or designee, would make blood collection unsafe

Individual participant data that underlie results in the publication, after deidentification.

Beginning 3 months following publication and available throughout period of funding of the International Maternal Pediatric Adolescent AIDS Clinical Trial (IMPAACT) Network by NIH.

• With whom? Researchers who provide a methodologically sound proposal for use of the data that is approved by the IMPAACT Network.
• For what types of analyses? To achieve aims in the proposal approved by the IMPAACT Network.
• By what mechanism will data be made available? Researchers may submit a request for access to data using the IMPAACT "Data Request" form at: https://www.impaactnetwork.org/studies/submit-research-proposal. Researchers of approved proposals will need to sign an IMPAACT Data Use Agreement before receiving the data."