Safety and Pharmacokinetics of Raltegravir in HIV-1-Exposed Newborn Infants at Risk of Acquiring HIV-1 Infection

• Status: Completed
• Trial end date: 2018-04-20
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
• Treatments: Raltegravir Potassium

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).