Dual bNAb Treatment in Children

This study will evaluate the impact of two broadly neutralizing antibodies, VRC01LS and 10-1074, on the maintenance of HIV suppression in a cohort of early-treated children in Botswana.

The primary objectives are as follows:

• To conduct an interventional clinical trial to determine the safety, pharmacokinetics, dosing and antiviral efficacy of up to 24 weeks of maintenance VRC01LS and 10-1074 immunotherapy in early-treated HIV-1 infected children in Botswana.
• To evaluate effects of treatment with VRC01LS and 10-1074 on the size and cellular composition of residual viral reservoirs.
• To investigate the influence of VRC01LS and 10-1074 treatment on the magnitude and quality of antiviral innate and adaptive immune responses.

The study includes 4 steps: the pharmacokinetics (PK) Step, Step 1, Step 2, and Step 3. In the PK Step, antiretroviral treatment (ART) is continued and 12 study participants will undergo safety and PK testing, 6 for each bNAb used in the study (10-1074 and VRC01LS). In Step 1, ART is continued and dual bNAb treatment occurs, with PK confirmation of dual bNAb dosing for the first 6 participants in Step 1. In Step 2, ART is withdrawn and dual bNAb maintenance treatment occurs. In Step 3, dual bNAbs will be discontinued and participants will be re-started on ART.

Participants will be in the study for a minimum of 56 weeks, and a maximum of 98 weeks for those who start in the PK step and continue through the study.

Inclusion criteria

for PK Step*:

• On ART for at least 96 weeks
• Greater than or equal to 96 weeks and less than 5 years of age at enrollment
• HIV RNA less than 40 copies/mL for at least 24 weeks prior to entry
• Ability to remain in close study follow-up for at least 12 weeks
• Willingness to receive IV infusions of bNAbs
• Willingness to provide signed informed consent (by the parent/guardian)

• *It is anticipated that all children in PK Step will be from Early Infant Treatment (EIT) Study (NCT02369406); however, up to 4 HIV+ children outside the PK Study (age range 2-5 years) may participate in the PK Step if otherwise eligible and if EIT children are unavailable.

Inclusion criteria

for Entry into Step 1 (followed by participation in Steps 2-3):

• EIT Study participant (NCT02369406)
• On ART for at least 96 weeks
• Greater than or equal to 96 weeks and less than 7 years of age at enrollment
• HIV RNA less than 40 copies/mL for at least 24 weeks prior to entry
• Ability to remain in close study follow-up for at least 56 weeks
• Willingness to receive IV infusions of bNAbs
• Willingness to provide signed informed consent (by the parent/guardian)

Exclusion criteria

• Medical condition making survival for at least 32 weeks unlikely
• Active tuberculosis or malignancy
• Actively breastfeeding
• Previous receipt of VRC01/VRC01LS or 10-1074 (except during the PK Step)