This is a study evaluating the safety and how the body handles a drug of potent broadly neutralizing anti HIV antibodies known as PGT121.414.LS when administered alone and in combination with VRC07523LS antibodies. Antibodies are protective proteins produced by the immune system. They attach to antigens (foreign substances) and remove them from the body. Children are still getting infected with HIV despite interventions to prevent mother to child transmission. This infection can occur during pregnancy, delivery or breastfeeding. According to UNAIDs statistics there were 160000 cases globally each year. Despite the advances made in prevention of passing of HIV from mother to child, before, during and after birth and breast milk transmission continue to occur for a variety of reasons. Reasons for continued transmission during childbirth period and early after the baby is born include birthing parents being diagnosed and treated late in pregnancy or having ART-resistant virus or poor adherence to ART. Further, even with effective treatments for infants born to birthing parents known to be living with HIV, acute

parental HIV acquisition during pregnancy or while breastfeeding is a situation in which the birthing parent is not diagnosed and treated soon enough to prevent all transmission to the now exposed infant. The study is being conducted in many countries globally. The protocol is not yet open to accrual. In Kenya the study is being conducted at the Kericho site. There are no other sites in Kenya participating in the study. Approximately 48 parent-infant pairs will be enrolled into the study

globally. The Kericho site anticipates to enroll up to 15 mother-infant pairs. Only mothers who intend to breastfeed their infants will be enrolled at the Kericho site. HIV positive pregnant women will be screened in third trimester or soon after delivery and enrolled within 72 hours of delivery. Mothers will not receive any study drugs. They will receive treatment as per the Kenya National Treatment guidelines. Infants who will qualify for the study will be initiated on the study drugs.

Infants will also receive Zidovudine and Nevirapine for prevention of mother to child transmission as per the Kenya National Guidelines. Infants will receive PGT121.414.LS antibodies alone or in combination with VRC07-523LS within 72 hours after delivery. This is the first time that PGT121.414.LS is being used in this age group and the first time that combination of two IPs is being used for the infants. Children will benefit from more frequent HIV testing and ancillary care that is provided through the study. The study may benefit the society by leading to availability of widened passing if HIV from parent to child prevention options for children born to HIV positive mothers.

Vertical transmission of HIV still occurs among the HIV exposed infants despite existing interventions with 160,000 children being diagnosed with HIV every year globally. Transmission resulting from breastfeeding is a major challenge to reducing rates of HIV among infants. Without (Antiretroviral Therapy) ART for the birthing parent or infant, transmission risk over the first year of life is between 5% and 15%. The risk can be reduced by exclusive breastfeeding, rather than mixed feeding, in the first six months and by provision of ART during the time of breastfeeding to either birthing parent or infant. Recommended therapy to prevent breast milk transmission is ART for the birthing parent during the period of breastfeeding and a period of (Nevirapine) NVP for the infant immediately after birth. However, even with treatment, transmission occurs in approximately 2% to 5% of infants in many countries. Vertical transmission is not limited to infants who breastfeed. As noted above, in both resource rich and resource-constrained settings, transmission continues to occur due to late diagnosis of the birthing parent’s HIV, no receipt of antiretroviral (ARV) drugs or reduced duration of ART during pregnancy, ART resistance, active viral replication during pregnancy, or prolonged rupture of membranes. HIV acquisition during pregnancy or during the time of breastfeeding is an additional significant contributor to vertical transmission. Therefore, it remains critically important to identify means to interrupt vertical transmission of HIV. Infants (less than 72 hours of age, gestational age at birth at least 36 weeks, birth weight at least 2 kg) who are born to people living with HIV-1 will be enrolled. The infant’s birthing parent will also be enrolled in the study but will not receive the broadly neutralizing monoclonal antibodies (PGT121.414.LS or VRC07-523LS). Participants will be enrolled in one of two sequential Cohorts. Participants in Cohort 1 will receive PGT121.414.LS alone and participants in Cohort 2 will receive PGT121.414.LS and VRC07523LS in combination. Within each Cohort, infants will be assigned to strata based on whether the birthing parent has indicated an intention to breastfeed (Stratum BF) or formula feed (Stratum FF). This is a first in age group and first time use of combination of the IPs in this age group. The Kericho site will enroll up to 15 mother infant pairs into the Breastfeeding stratum only of

both cohorts. The participants will be followed up for up to 96 weeks after enrollment. The study will evaluate the safety and pharmacokinetics (PK) of the potent, broadly neutralizing anti-HIV monoclonal antibodies (mAb) PGT121.414.LS alone and in combination with VRC07-523LS soon after birth in infants exposed to HIV-1