Evaluating the Safety and Antiviral Activity of Monoclonal Antibody VRC01 in HIV-Infected Infants Receiving Combination Antiretroviral Therapy

VRC01 is an experimental human immunoglobulin G1 (IgG1) monoclonal antibody. The purpose of
this study is to evaluate the safety and antiviral activity of VRC01 in HIV-1-infected
infants initiating cART within 12 weeks of birth.

The infants will be randomly assigned to either receive VRC01 (Arm 1) or not receive VRC01
(Arm 2). Infants in Arm 1 will receive VRC01 at study entry (Week 0) and Weeks 2, 6, and 10.
Infants in Arm 2 will receive no study product.

Participants will attend study visits at Weeks 1, 2, 3, 6, 7, 10, 11, 14, 16, 20, 24, 36, and
48. Visits will include physical examinations, blood and urine collection, and specimen
collection.

Infants' mothers may optionally be enrolled in the study for one-time specimen collection for
exploratory evaluations. Maternal study participation is not required for infant study
participation.

Study duration is approximately two years. Accrual is expected to require approximately one
year, and each infant will complete 48 weeks of follow-up.

Infant Inclusion Criteria:

All the criteria listed below must be met in order for infants to be included in this
study.

- Parent or legal guardian is willing and able to provide written informed consent for
infant participation in the study, including collection and storage of biological
specimens for exploratory virology and immunology investigations.

- Infant is within 12 weeks (84 days) of birth at study entry.

- Infant weighs at least 2500 g at study entry.

- Infant has confirmed HIV-1 infection based on positive results from two samples (whole
blood or plasma) collected at different time points using the following methods:

- One HIV DNA polymerase chain reaction (PCR)

- One quantitative HIV RNA PCR (above the limit of detection of the assay)

- One qualitative HIV RNA PCR

- One total HIV nucleic acid test

- At least one of the two samples must be tested in a Clinical Laboratory
Improvement Amendments (CLIA)-certified (U.S. sites) or DAIDS Virology Quality
Assurance program (VQA)-certified (non-U.S. sites) laboratory. For tests
performed in other (non-certified) settings, adequate source documentation
including the date of specimen collection, date of testing, test performed, and
test result must be available.

- Infant has the following laboratory values at screening (with samples collected for
testing within 30 days prior to entry):

- CD4 lymphocyte percentage greater than 15

- Severity grade 1 or lower hemoglobin, platelet count, and absolute neutrophil
count

- Severity grade 1 or lower alanine aminotransferase (ALT), aspartate
aminotransferase (AST), and alkaline phosphatase

- See Section 7.3 of the study protocol for guidance on severity grading.

- Infant's initial combination antiretroviral therapy (cART) regimen has been selected
and documented at study entry, prior to randomization, with the first dose taken on
the day of randomization or within 14 days prior to the day of randomization.

- Infant is expected to be available for 48 weeks of follow-up at study entry.

- Parent or legal guardian is willing and able to complete reactogenicity memory aids
for study purposes, based on parent/guardian report.

Infant Exclusion Criteria:

Infants must be excluded from the study if any of the following are identified at any time
prior to randomization:

- Infant or infant's mother received exclusionary active or passive HIV-specific
immunotherapy, as follows:

- Infant received any active or passive HIV-specific immunotherapy prior to study
entry.

- Infant's mother received any active HIV-specific immunotherapy prior to infant
study entry.

- Infant's mother received any passive HIV-specific immunotherapy within two years
prior to infant study entry.

- If infant's mother is breastfeeding: mother is planned to receive any active or
passive HIV-specific immunotherapy at any time during infant study participation.

- Infant initiated a combination of three or more ARVs, all at or above recommended
treatment doses, within 48 hours of birth. Recommended treatment doses are as follows:

- Nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs): As per World
Health Organization (WHO) or U.S. Department of Health and Human Services
pediatric treatment guidelines

- Nevirapine (NVP): At least 8 mg for infants weighing up to 2 kg, at least 12 mg
for infants weighing more than 2 kg

- Lopinavir/ritonavir (LPV/r): 300 mg/75 mg per m^2 of body surface area twice
daily

- All other ARVs: Consult with IMPAACT 2008 Clinical Management Committee (CMC)

- Note: Regimens comprised of fewer than three ARVs, or of three ARVs with at least
one ARV below the recommended treatment dose, are permitted, even if initiated
within 48 hours of birth.

- Infant received within 30 days prior to study entry, or is identified as requiring,
any of the following:

- Chronic (more than 14 days) systemic steroid treatment

- Immunoglobulin treatment

- Immunomodulators (interleukins, interferons, cyclosporin)

- Cytotoxic chemotherapy

- Treatment for active tuberculosis (TB) disease

- Any investigational agent

- Note: Treatment for latent TB infection is permitted.

- Infant has any documented or suspected clinically significant medical illness,
clinically significant congenital anomaly, or immediately life-threatening condition
that, in the opinion of the site investigator or designee, would interfere with the
infant's ability to comply with study requirements.

- Infant has any other 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.

Maternal Inclusion Criteria:

The mothers of enrolled infants will be asked to consent to blood collection and storage
for this study. The following criteria must be met in order for mothers to undergo blood
collection for this purpose:

- Mother is willing and able to provide independent written informed consent for blood
collection and storage for virology and immunology investigations.

- Mother has no documented or suspected condition that, in the opinion of the site
investigator or designee, would make blood collection unsafe.