Evaluating the Safety and Pharmacokinetics of VRC01, VRC01LS, and VRC07-523LS, Potent Anti-HIV Neutralizing Monoclonal Antibodies, in HIV-1-Exposed Infants

VRC01, VRC01LS, and VRC07-523LS are anti-HIV neutralizing monoclonal antibodies that may help
prevent mother-to-child transmission of HIV. This study will enroll HIV-infected mothers who
are at increased risk of passing HIV on to their children. The purpose of this study is to
assess the safety and PK of VRC01, VRC01LS, and VRC07-523LS in HIV-exposed infants.

This study will enroll mother-infant pairs into five groups. Infants enrolled in Dose Group 1
and Dose Group 2 will receive a single VRC01 injection less than 72 hours after birth.
Infants in Dose Group 3 will receive a VRC01 injection less than 5 days after birth. They
will then receive additional VRC01 injections monthly for at least 6 months and no more than
18 months while breastfeeding.

Dose Groups 4 and 5 will each enroll infants into two cohorts: Cohort 1 (non-breastfeeding)
or Cohort 2 (breastfeeding). Infants in Dose Group 4, Cohort 1 will receive a single VRC01LS
injection less than 72 hours after birth. Infants in Dose Group 4, Cohort 2 will receive an
initial VRC01LS injection no longer than 5 days after birth, and a second VRC01LS injection
at Week 12 if they are still breastfeeding. Infants in Dose Group 5, Cohort 1 will receive a
single VRC07-523LS injection less than 72 hours after birth. Infants in Dose Group 5, Cohort
2 will receive an initial VRC07-523LS injection no longer than 5 days after birth, and a
second VRC07-523LS injection at Week 12 if they are still breastfeeding.

The mothers will not receive any VRC01, VRC01LS, or VRC07-523LS injections. At study entry,
all mothers will undergo a medical history review and a blood collection. Infants in Dose
Groups 1 and 2 will attend several study visits through Week 48. Infants in Dose Group 3, 4,
and 5 will attend several study visits through Week 96. Visits will include a medical history
review, physical examination, blood collection, and oral fluid collection.

Maternal Inclusion Criteria:

- Documentation of HIV infection. Documentation of HIV-1 infection is defined as
positive results from two samples collected at different time points. All samples
tested must be whole blood, serum, or plasma. For this protocol, the results for
sample #2 may be pending at the time of enrollment. Results documented in the clinical
record from past testing may be used to satisfy the criteria for documentation of
HIV-1 infection. More information on this criterion can be found in the protocol.

- Greater than or equal to 18 years of age

- Able and willing to provide signed informed consent for herself and her infant

Maternal Exclusion Criteria:

- Prior participation in any HIV-1 vaccine trial

- Receipt of any other active or passive HIV immunotherapy or investigational product
during this pregnancy. (Note that administration of Food and Drug Administration
[FDA]-approved antiretroviral [ARV] drugs when used to treat disease or prevent
mother-to-child transmission are not considered investigational.)

- Documented or suspected serious medical illness or immediate life-threatening
condition (other than HIV infection) in the mother that may interfere with the ability
to complete study requirements, as judged by the examining clinician

Infant Inclusion Criteria:

- Born to an HIV-1-infected woman who meets all maternal inclusion/exclusion criteria
listed above

- Gestational age, by best obstetrical, ultrasound, or infant exam, greater than or
equal to 36 weeks

- Birth weight greater than or equal to 2.0 kg

- Allowable infant age at the time of enrollment is dependent on the Dose Group and
Cohort:

- Dose Groups 4 and 5 (Cohort 1): Less than 72 hours of age, and anticipated
availability to receive VRC01LS or VRC07-523LS immunization at less than 72 hours
after birth.

- Dose Groups 4 and 5 (Cohort 2): Less than or equal to 5 days of age, and
anticipated availability to receive VRC01LS or VRC07-523LS immunization no more
than 5 days after birth.

- At increased risk of HIV acquisition defined as documentation of one or more of the
following risk factors:

- Dose Groups 4 and 5 (Cohort 1), only:

- Mother received no antiretroviral therapy (ART) during pregnancy or mother began
or reinitiated ART (after an interruption of greater than 14 days), during the
third trimester of pregnancy; or

- Mother with any detectable viral replication (HIV RNA above the limit of
detection) at last measurement prior to delivery determined within 30 days of
delivery; or

- Prolonged rupture of membranes (greater than 12 hours); or

- Mother with documented* 2-class resistant HIV infection, which may include
historical documentation of lack of response

- Women who have a documented history of virologic failure while on
non-nucleoside reverse transcriptase inhibitors (NNRTIs) but who had no
resistance testing at the time of viral failure will be considered to have
NNRTI-documented resistance.

- Dose Groups 4 and 5 (Cohort 2), only (African sites):

- Mother intends to breastfeed

Infant Exclusion Criteria:

- Receipt of any other active or passive HIV immunotherapy or investigational product
other than the study vaccine (Note: Infant prophylaxis with any licensed ARV drugs
clinically prescribed to prevent mother-to-child HIV transmission are not considered
investigational.)

- Receipt of or anticipated need for blood products, immunoglobulin, or
immunosuppressive therapy. This includes infants who require hepatitis B
immunoglobulin (HBIG) but does not require exclusion of infants who receive hepatitis
B vaccine in the newborn period.

- Documented or suspected serious medical illness, serious congenital anomaly, or
immediate life-threatening condition in the infant that may interfere with the ability
to complete study requirements, as judged by the examining clinician

- Any requirement for supplemental oxygen beyond 24 hours of life or requiring
supplemental oxygen at the time of the VRC01, VRC01LS, or VRC07-523LS dose

- Baseline laboratory results:

- Hemoglobin less than 12.0 g/dL

- Platelet count less than 100,000 cells/mm^3

- Absolute neutrophil count: for infants less than or equal to 24 hours old, less
than 4,000 cells/mm^3; for infants greater than 24 hours old, less than 1,250
cells/mm^3

- Serum glutamic pyruvic transaminase (SGPT) (alanine aminotransferase [ALT])
greater than or equal to 1.25 times upper limit of age adjusted normal

- Dose Groups 4 and 5 (Cohort 1), only: Infant is breastfeeding at time of enrollment or
mother has indicated an intention to initiate breastfeeding. Note: if a child is
breastfed prior to known maternal diagnosis (in the case of a woman diagnosed in the
intrapartum period), the child is still eligible as long as breastfeeding is stopped
by the time the child is enrolled and there is no plan to resume breast milk feeding.