Safety and Pharmacokinetics Study of PGT121.414.LS Alone and in Combination With VRC07-523LS in Infants Exposed to HIV-1

This is an open-label, phase I study of the potent, broadly neutralizing anti-HIV monoclonal antibodies (mAb) PGT121.414.LS alone and in combination with VRC07-523LS administered soon after birth in infants exposed to HIV-1. The study is designed to assess the safety and pharmacokinetics (PK) profile of one and two subcutaneous (SC) doses of PGT121.414.LS alone or in combination with VRC07-523LS through Week 12 and Week 24, respectively.

Inclusion criteria

• Birthing parent is of legal age or circumstance to provide independent informed consent and is willing and able to provide written informed consent for themselves and permission for their infant's participation in this study.
• Birthing parent has confirmed HIV-1 infection based on positive test results from two samples collected from two separate blood collection tubes.
• Infant was singleton or twin.
• Infant's gestational age at birth was at least 36 weeks.
• At birth, infant's weight was at least 2 kg.
• At entry, infant is less than 72 hours of age and is anticipated to receive study product within 72 hours after birth.
• At screening, infant has the following laboratory test results:

• Hemoglobin, normal or grade 1 (≥13 g/dL or ≥8.05 mmol/L)
• Platelets, normal or grade 1 (≥100,000 cells/mm3 or ≥100.000 x10^9 cells/L)
• Absolute neutrophil count (ANC), normal or grade 1

• ≤24 hours old (≥4,000 cells/mm3 or ≥4.000 x10^9 cells/L)
• >24 hours old (≥1,250 cells/mm3 or ≥1.250 x10^9 cells/L)
• Alanine transaminase (ALT), normal (<1.25 x ULN)
• At entry, infant is generally healthy as determined by the site investigator based on review of all available medical history information and physical examination findings.
• Cohorts 1 and 2, Strata BF only: At entry, infant is breastfeeding or the birthing parent has indicated an intention to initiate breastfeeding.
• Cohorts 1 and 2, Strata FF, only: At entry, infant is not breastfeeding and the birthing parent has indicated no intention to breastfeed.
• At entry, infant is at increased risk of HIV acquisition.

Cohorts 1 and 2, Strata FF only:

• Birthing parent had acute HIV during this pregnancy; or
• Birthing parent with detectable viral replication (plasma HIV RNA results at least 50 copies/mL) during pregnancy who did not have confirmed viral suppression, defined as at least two consecutive plasma HIV RNA results less than 50 copies/mL from specimens obtained at least four weeks apart with the latest result within four weeks prior to delivery; or
• Birthing parent not receiving appropriate ART for at least two weeks, with any part of the two-week period occurring within four weeks prior to delivery, based on birthing parent's report or available medical records.

Cohorts 1 and 2, BF only:

• Per birthing parent's report, intends to breastfeed

Exclusion criteria

• Birthing parent has received any investigational product during this pregnancy.
• Infant has received any active or passive HIV immunotherapy or any investigational product.
• At entry, infant with a documented positive HIV Nucleic Acid Test (NAT) result.
• Birthing parent or infant has any 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.