PrEP in Breastfeeding Study
PrEP in Breastfeeding Study
The purpose of this study is to quantify the magnitude and extent of infant exposure to daily
 emtricitabine (FTC) /tenofovir disoproxil fumarate (TDF) via maternal breastmilk when taken
 pre-exposure prophylaxis (PrEP) by lactating HIV-uninfected women. The primary outcome is the
 steady state concentrations of emtricitabine and tenofovir in the infant plasma.
This is prospective, short-duration, open-label, single-arm, repeat-dose, pharmacokinetic
 study of daily FTC/TDF PrEP among HIV-uninfected lactating mother-infant pairs. PrEP will be
 administered to women through daily directly observed therapy for 10 consecutive days -
 sufficient to reach steady-state but discontinuing thereafter. No drug will be administered
 to the infant directly. Co-formulated FTC and TDF were dosed at 200 mg daily and 300 mg
 daily, respectively. The overall goal is to quantify the magnitude and degree to which
 breastfeeding infants are exposed to FTC/TDF when used as PrEP by HIV-uninfected lactating
 women. Maternal blood and breastmilk samples will be obtained concurrently (i.e., within 30
 minutes of each other) regardless of the timing of food intake (i.e., non-fasting) on the 7th
 and 10th day. Peak samples will be obtained 1-2 hours after the maternal directly observed
 PrEP and trough samples were obtained at the end of the dosing interval (i.e., 23 to 24 hours
 after directly observed PrEP dose). A single infant blood sample will be obtained after the
 maternal 7th directly observed PrEP dose.

 We will conduct quantitative measurements and analyses of infant plasma drug concentrations,
 infant-plasma to breastmilk and breastmilk to maternal plasma drug concentration ratios to
 characterize FTC and TDF transmission to breast feeding infants. Tenofovir and emtricitabine
 concentrations in plasma and breastmilk will be quantified via previously validated liquid
 chromatographic-tandem mass spectrometric (LC-MS/MS) methods in accordance with the
 recommendations included in the US Food and Drug Administration, Guidance for Industry,
 Bioanalytical Method Validation guidelines.
Inclusion Criteria:

 For infant's mother and father

 -  Able and willing to provide informed consent for the infant to participate in the
 study

 -  Of legal age ≥18 years to consent

 For HIV-uninfected mother, in addition to the criteria noted immediately above:

 -  Willing to provide breast milk samples and breastfeed during the duration of the study
 0-24 weeks postpartum

 -  Breastfeeding an infant

 -  HIV-uninfected based on negative HIV rapid tests, both at study screening and at the
 enrollment visit

 -  Adequate renal function, defined by normal creatinine levels and estimated creatinine
 clearance ≥60 mL/min

 -  Not infected with hepatitis B virus, as determined by a negative hepatitis B surface
 antigen test

 -  Not currently using PrEP

 -  Note: single mothers will be eligible to participate in this study. Where possible the
 father's permission was be obtained. When the father is unknown, incompetent,
 deceased, or not reasonably available, or when only the mother has the legal
 responsibility for the care and custody of the child, infant participation will be
 based on the mother's consent and documentation will be added to file.

 For infant

 -  Infant born to eligible women (both male and female infants will be included)

 -  Age 0-24 weeks

 -  Otherwise infant has no serious infections or active clinically significant medical
 problems

 Exclusion Criteria:

 -  Women breastfeeding more than one child

 -  Preterm babies or infants with low birth weight (i.e. ≤2000mg)