Safety and Pharmacokinetics of Raltegravir in HIV-1-Exposed Newborn Infants at Risk of Acquiring HIV-1 Infection
HIV Infections
About this trial
This is an interventional treatment trial for HIV Infections
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).
Sites / Locations
- Usc La Nichd Crs
- Children's National Med. Ctr. Washington DC NICHD CRS
- Univ. of Florida Jacksonville NICHD CRS
- Rush Univ. Cook County Hosp. Chicago NICHD CRS
- Lurie Children's Hospital of Chicago (LCH) CRS
- Boston Medical Center Ped. HIV Program NICHD CRS
- Bronx-Lebanon Hospital Center NICHD CRS
- St. Jude Children's Research Hospital CRS
- Hospital Federal dos Servidores do Estado NICHD CRS
- Hosp. Geral De Nova Igaucu Brazil NICHD CRS
- Univ. of Sao Paulo Brazil NICHD CRS
- University of Puerto Rico Pediatric HIV/AIDS Research Program CRS
- Umlazi CRS
- Fam-Cru Crs
- Siriraj Hospital ,Mahidol University NICHD CRS
Arms of the Study
Arm 1
Arm 2
Experimental
Experimental
Cohort 1
Cohort 2
HIV-1-exposed full-term infants. Infants received two single doses of RAL: first dose within 48 hours of birth and second dose at 7-10 days of life: RAL-naive: 3 or 2 mg/kg within 48 hours of birth and 3 mg/kg at 7-10 days of life. RAL-exposed: 1.5 mg/kg within 48 hours of birth and 3 mg/kg at 7-10 days of life.
HIV-1-exposed full-term infants. Daily RAL through 6 weeks of life with first dosing within 48 hours of birth and between 12-60 hours of birth for in utero RAL-naive and RAL-exposed infants, respectively. Daily RAL through 6 weeks of life: 1.5 mg/kg once daily during Days 1-7 of life, 3.0 mg/kg twice daily during Days 8-28 of life, and 6.0 mg/kg twice daily during Days 29-42 of life.