Principal Investigator: Roger Shapiro, MD,MPH

Study Objectives:

Primary Objectives

• (Step 1a): To describe the safety and pharmacokinetics of bNAb immunotherapy with VRC07-523LS, PGDM1400LS and PGT121.414.LS when added to existing effective ART in early-treated children living with HIV-1 in Botswana:
•  (Step 1b): To describe the safety of up to 24 weeks of bNAb immunotherapy with VRC07-523LS, PGDM1400LS, and PGT121.414.LS when added on a rotating schedule to existing effective ART in early-treated children living with HIV-1 in Botswana.
•  (Step 2): To describe the safety, maintenance of virologic suppression, and CD4 cell count preservation of 24 weeks of maintenance VRC07-523LS, PGDM1400LS and PGT121.414.LS immunotherapy alone, following the discontinuation of ART in selected early-treated children living with HIV-1 in Botswana.
•  (Step 3): To describe the safety, maintenance of virologic suppression, and CD4 cell count preservation of up to 48 weeks of ATI (with no ART or bNAbs) among participants who meet specified criteria for an ATI.

Secondary Objectives

• To measure the proportion of participants with viral rebound defined as a single plasma HIV-1 RNA ≥400 copies/mL at/prior to 48 weeks of bNAb-only treatment (for those who continue bNAb-only treatment beyond 24 weeks).
• To monitor and report time to re-suppression of plasma HIV-1 RNA following re-initiation of ART, for participants who experience viral rebound on bNAbs alone or during ATI.
• To measure the size of residual viral reservoirs during each step of the study. Comparisons will include change during triple bNAbs + ART; change during triple bNAbs alone; change during ATI; and change during entire study.

Study Design: This is a Phase I/II, open-label study of treatment with three bNAbs for virally suppressed children and young adults living with HIV-1 in Botswana, using VRC07-523LS, PGDM1400LS and PGT121.414.LS; the study will also include an ATI for selected participants.

Up to approximately 41 participants may be enrolled (35 may enter in Step 1 and approximately six may enter Step 3 directly). Participants will be enrolled at two NIAID-approved clinical research sites in Botswana: Gaborone (CRS #31833) and Francistown (CRS #31891).

Study Population:

• Children living with HIV aged 24 weeks up to 12 years with HIV-1 RNA that has been suppressed to <40 copies/mL for at least 24 weeks prior to entry.
• Adolescents/young adults aged between 13 to 25 years of age living with HIV, with HIV-1 RNA that has been suppressed to <40 copies/mL for at least 96 weeks prior to entry.

Sample Size:

This study will be conducted among approximately 41 participants who were previously enrolled in the EIT/Tatelo, or Moso Cohort Study, or Adolescent Cohort Study (Phodiso Study).

Study duration: 5 years

Sponsor: National Institute of Allergy and Infectious Diseases