Clinical trial NCT02776748: PrEP in Breastfeeding Study
Official title: An Open-label, Short-duration, Repeat-dose Study of Breastmilk Excretion and Infant Absorption of Daily Oral Tenofovir Disoproxil Fumarate/Emtricitabine When Used by HIV-uninfected Lactating Women
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: HIV Pre-exposure Prophylaxis During Breastfeeding
Keywords: Tenofovir disoproxil
Pre-exposure prophylaxis
Breastfeeding
Emtricitabine
Tenofovir
Post-partum
HIV prevention
Women
Pharmacokinetics
Lead sponsor: University of Washington
Sponsor class: OTHER
Collaborators: name: Bill and Melinda Gates Foundation
First posted: 2016-05-18
Enrollment: 50
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: PREVENTION

Brief summary: 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.

Detailed 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.

Eligibility criteria: 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)

Primary outcomes:
measure: Steady state plasma concentrations of emtricitabine and tenofovir in the infants of breastfeeding women using PrEP: Quantity of PrEP medications in the infant plasma.
timeFrame: Time averaged: 10 days
measure: Steady state plasma concentrations of emtricitabine and tenofovir in the infants of breastfeeding women using PrEP: Detectable and quantifiable concentrations of PrEP medications in the infant plasma.
timeFrame: Time averaged: 10 days
measure: Steady state concentrations of emtricitabine and tenofovir in plasma of HIV-uninfected women using PrEP.
timeFrame: Time averaged: 10 days
measure: Steady state concentrations of emtricitabine and tenofovir in breastmilk of HIV-uninfected women using PrEP.
timeFrame: Time averaged: 10 days
measure: Infant plasma-to-maternal breast milk emtricitabine and tenofovir concentration ratios.
timeFrame: Time averaged: 10 days
measure: Infant daily dose of tenofovir and emtricitabine received from breastmilk
timeFrame: Time averaged: 10 days
measure: Infant dose fraction for tenofovir and emtricitabine.
timeFrame: Time averaged: 10 days
measure: Maternal breastmilk emtricitabine and tenofovir to plasma concentration ratios.
timeFrame: Time averaged: 10 days
measure: Serious adverse events in infants of breastfeeding HIV-uninfected women using PrEP.
timeFrame: Time averaged: 10 days
measure: Serious adverse events in breastfeeding HIV-uninfected women using PrEP.
timeFrame: Time averaged: 10 days
Secondary outcomes:
Other outcomes:
Locations:
city: Thika
country: Kenya
facility: Partners in Prevention-Thika
city: Kampala
country: Uganda
facility: Partners in Prevention-Infectious Diseases Institute LTD
Study officials:
affiliation: University of Washington
name: Jared M Baeten, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Washington
name: Kenneth K Mugwanya, MBChB, MS
role: STUDY_DIRECTOR
References:
citation: Mugwanya KK, Hendrix CW, Mugo NR, Marzinke M, Katabira ET, Ngure K, Semiyaga NB, John-Stewart G, Muwonge TR, Muthuri G, Stergachis A, Celum CL, Baeten JM. Pre-exposure Prophylaxis Use by Breastfeeding HIV-Uninfected Women: A Prospective Short-Term Study of Antiretroviral Excretion in Breast Milk and Infant Absorption. PLoS Med. 2016 Sep 27;13(9):e1002132. doi: 10.1371/journal.pmed.1002132. eCollection 2016 Sep.