Safety and Pharmacokinetics of Raltegravir in HIV-1-Exposed Newborn Infants at Risk of Acquiring HIV-1 Infection
Condition: HIV Infections
MeSH terms: Infections; Communicable Diseases
Intervention: Raltegravir
Intervention description: RAL was given as oral granules for suspension.
Intervention MeSH terms: Raltegravir Potassium
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 52.0
Sex: All
Healthy volunteers: No

Summary:

      The purpose of this study was to evaluate the safety and pharmacokinetics (PK) of raltegravir
      (RAL) when given to HIV-1-exposed, normal birth weight newborn infants at risk of acquiring
      HIV-1 infection. (PK is the study of the time course of absorption, distribution, metabolism,
      and excretion of drugs in the body.) The primary goal of this study was to determine a dose
      of RAL that was safe and met the PK targets for infants when administered during the first 6
      weeks of life in addition to standard of care antiretroviral (ARV) agents for prevention of
      perinatal transmission.
    

Eligibility criteria:

        Maternal Inclusion Criteria:

          -  Mother is living with HIV and either i) known to have HIV diagnosis prior to labor
             (testing obtained and designated per local SOC in the medical record and either on or
             recently started CART prior to delivery) or ii) identified as having HIV diagnosis at
             the time of labor or in the immediate postpartum period. More information on this
             criterion can be found in the protocol.

          -  Risk of mothers transmitting HIV to their infants:

               -  Cohort 1 and Cohort 2 (RAL-naive): Mother living with HIV is at "high risk" of
                  transmitting HIV to infant as evidenced by any of the following: Mother has not
                  received any ARV therapy during the current pregnancy prior to the onset of labor
                  and delivery; HIV RNA level greater than 1000 copies/mL within 4 weeks (28 days)
                  prior to delivery; receipt of ARV for less than 4 weeks (28 days) before
                  delivery; on ARVs for 4 weeks or longer but has not taken any ARV for more than 7
                  days prior to delivery; or mother has documented drug resistant virus to at least
                  one class of ARV drugs.

               -  Cohort 2 RAL-exposed: there was no requirement that the mother living with HIV is
                  at "high-risk" of transmitting HIV to her infant.

          -  Maternal written informed consent for study participation

        Maternal Exclusion Criteria:

          -  Known maternal-fetal blood group incompatibility as evidenced by the presence of an
             unexpected clinically significant maternal red cell antibody that is known to be
             capable of causing hemolytic disease of the fetus/newborn

          -  Mother will be receiving RAL as part of her combination antiretroviral (cART) regimen
             after delivery and intending to breastfeed her infant

          -  For Cohort 1 and Cohort 2 RAL-naive groups:

               -  Cohort 1 RAL-naive: Mother who received RAL prior to and through delivery unless
                  last RAL dosing during prenatal period was >7 days prior to delivery

               -  Cohort 2 RAL-naive: Mother who received RAL prior to and through delivery

        Infant Inclusion Criteria:

          -  Age at enrollment (Note: The full-term infants were HIV-exposed and may have received
             standard of care ARV prophylaxis/treatment before enrollment):

               -  Cohort 1 and Cohort 2 RAL-naive: Aged 48 hours or less.

               -  Cohort 2 RAL-exposed: Aged 60 hours or less.

          -  Infant gestational age at birth at least 37 weeks

          -  No known severe congenital malformation or other medical condition not compatible with
             life or that would interfere with study participation or interpretation, as judged by
             the examining clinician

          -  Birth weight at least 2 kg

          -  Able to take oral medications

          -  Parent or legal guardian able and willing to provide signed informed consent

          -  For Cohort 1 and Cohort 2 RAL-exposed groups:

               -  Cohort 1 RAL-exposed: Infants born to mothers who received RAL during pregnancy
                  with last dose taken within 7 days before delivery.

               -  Cohort 2 RAL-exposed: Infants born to a mother who received at least one dose of
                  RAL within 2 to 24 hours prior to delivery.

        Infant Exclusion Criteria:

          -  Infant with bilirubin exceeding the American Academy of Pediatrics guidelines for
             phototherapy, using the infant's gestational age and risk factors as described in the
             protocol.

          -  Clinical evidence of renal disease such as edema, ascites, or encephalopathy.

          -  Receipt of disallowed medications (phenytoin, phenobarbital, or rifampin).