PrEP in Breastfeeding Study

University of Washington

Status and phase

Completed

Phase 3

Phase 2

Conditions

HIV Pre-exposure Prophylaxis During Breastfeeding

Treatments

Drug: FTC/TDF PrEP

Study type

Interventional

Funder types

Other

Identifiers

NCT02776748

46363

Details and patient eligibility

About

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.

Full description

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.

Enrollment

50 patients

Sex

Female

Ages

18+ years old

Volunteers

No Healthy Volunteers

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