Evaluating the Safety and Pharmacokinetics of VRC01, VRC01LS, and VRC07-523LS, Potent Anti-HIV Neutralizing Monoclonal Antibodies, in HIV-1-Exposed Infants
Condition: HIV Infections
MeSH terms: HIV Infections
Intervention: VRC01; VRC01LS; VRC07-523LS
Intervention description: Administered by subcutaneous injection in the thigh; Administered by subcutaneous injection in the thigh; Administered by subcutaneous injection in the thigh
Phase: Phase 1
Study type: Interventional
Primary purpose: Prevention
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 83.0
Sex: All
Minimum age: 0 Days
Maximum age: 5 Days
Healthy volunteers: No

Summary:

      The purpose of this study was to assess the safety and pharmacokinetics (PK) of three
      monoclonal antibodies, VRC01, VRC01LS, and VRC07-523LS, in HIV-exposed infants who are at
      increased risk of mother-to-child HIV transmission.
    

Eligibility criteria:

        Maternal Inclusion Criteria:

          -  HIV infection

          -  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 were not considered investigational.)

          -  Documented or suspected serious medical illness or immediate life-threatening
             condition (other than HIV infection) in the mother that may have interfered with the
             ability to complete study requirements, as judged by the examining clinician

        Infant Inclusion Criteria:

          -  Born to an HIV-1-infected woman who met 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 was dependent on the Dose Group and
             Cohort:

               -  Dose Groups 1, 2, 4 and 5 (Cohort 1): Less than 72 hours of age, and anticipated
                  availability to receive VRC immunization at less than 72 hours after birth.

               -  Dose Groups 3, 4 and 5 (Cohort 2): Less than or equal to 5 days of age, and
                  anticipated availability to receive VRC 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 1, 2, 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 have included
                  historical documentation of lack of response

                    -  Women who had 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 were considered to have
                       NNRTI-documented resistance.

          -  Dose Groups 3, 4 and 5 (Cohort 2), only (African sites):

               -  Mother intended 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 were not considered
             investigational.)

          -  Receipt of or anticipated need for blood products, immunoglobulin, or
             immunosuppressive therapy. This included infants who required hepatitis B
             immunoglobulin (HBIG) but did not require exclusion of infants who received 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 have interfered 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) greater than or equal to 1.25 times
                  upper limit of age adjusted normal

          -  Dose Groups 1, 2, 4 and 5 (Cohort 1), only: Infant was breastfeeding at time of
             enrollment or mother had indicated an intention to initiate breastfeeding. Note: if a
             child was breastfed prior to known maternal diagnosis (in the case of a woman
             diagnosed in the intrapartum period), the child was still eligible as long as
             breastfeeding was stopped by the time the child was enrolled and there was no plan to
             resume breast milk feeding.