PrEP in Breastfeeding Study

NCT02776748 | Completed Phase 2

• 1 other identifier: 46363
• Study Type: interventional
• Target: 50
• Locations: 2 countries
• Sites: 2

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.

Conditions

HIV Pre-exposure Prophylaxis During Breastfeeding

Keywords

Tenofovir disoproxil; Pre-exposure prophylaxis; Breastfeeding; Emtricitabine; Tenofovir; Post-partum; HIV prevention; Women; Pharmacokinetics

Outcome Measures

Primary Outcomes (10)

• Steady state plasma concentrations of emtricitabine and tenofovir in the infants of breastfeeding women using PrEP: Quantity of PrEP medications in the infant plasma.

  Infant exposure measured as median (interquartile range) concentrations of emtricitabine and tenofovir infant plasma.

  Time averaged: 10 days

• 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.

  Measure the proportion of infant plasma samples with concentrations of emtricitabine and tenofovir below the assay lower limit of quantification.

  Time averaged: 10 days

• Steady state concentrations of emtricitabine and tenofovir in plasma of HIV-uninfected women using PrEP.

  Measure median (interquartile range) concentrations of emtricitabine and tenofovir in maternal plasma.

  Time averaged: 10 days

• Steady state concentrations of emtricitabine and tenofovir in breastmilk of HIV-uninfected women using PrEP.

  Measure median (interquartile range) concentrations of emtricitabine and tenofovir in breast milk.

  Time averaged: 10 days

• Infant plasma-to-maternal breast milk emtricitabine and tenofovir concentration ratios.

  Measure median (interquartile range) infant plasma-to-maternal breast milk emtricitabine and tenofovir concentration ratios.

  Time averaged: 10 days

• Infant daily dose of tenofovir and emtricitabine received from breastmilk

  We will compute the infant drug dose received from breastmilk per day (infant Computed as the product of breast milk tenofovir and emtricitabine concentrations and the estimated volume of breast milk consumed by infant daily. We will assume the daily amount of breast milk consumed by the infant to be 150 mL/kg/day, the standardized milk consumption of the average milk intake of a fully breast-fed infant. Measure median (interquartile range) infant daily dose for tenofovir and emtricitabine from breastmilk.

  Time averaged: 10 days

• Infant dose fraction for tenofovir and emtricitabine.

  Infant dose fraction (i.e., exposure index) represents the daily amount of drug dose an infant would ingest from breast milk as a percentage of the recommended pediatric therapeutic daily dose. Infant dose fraction will be computed as as: infant dose fraction (%) = infant dose from breast milk \*100/infant therapeutic dose. Measure median (interquartile range) infant dose fraction.

  Time averaged: 10 days

• Maternal breastmilk emtricitabine and tenofovir to plasma concentration ratios.

  Measure median (interquartile range) of maternal breastmilk emtricitabine and tenofovir to plasma concentration ratios.

  Time averaged: 10 days

• Serious adverse events in infants of breastfeeding HIV-uninfected women using PrEP.

  Number of infants with serious adverse effects.

  Time averaged: 10 days

• Serious adverse events in breastfeeding HIV-uninfected women using PrEP.

  Number of women with serious adverse effects.

  Time averaged: 10 days

Study Arms (1)

FTC-TDF

OTHER

Emtricitabine/Tenofovir Disoproxil Fumarate (FTC/TDF) PrEP: 200mg FTC /300 mg TDF

Drug: FTC/TDF PrEP

Interventions

FTC/TDF PrEP DRUG

Daily oral directly observed FTC/TDF PrEP administered to breastfeeding HIV-uninfected women

Also known as: Truvada PrEP

FTC-TDF

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• Women breastfeeding more than one child
• Preterm babies or infants with low birth weight (i.e. ≤2000mg)

Sponsors & Collaborators

• University of Washington: lead
• Bill and Melinda Gates Foundation: collaborator

Study Sites (2)

Partners in Prevention-Thika

Thika, Kenya

Location

Partners in Prevention-Infectious Diseases Institute LTD

Kampala, Uganda

Location

Related Publications (1)

• 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.

  PMID: 27676257 DERIVED

MeSH Terms

Conditions

Breast Feeding

Condition Hierarchy (Ancestors)

Feeding Behavior; Behavior

Study Officials

• Jared M Baeten, MD, PhD

  University of Washington

  PRINCIPAL INVESTIGATOR

• Kenneth K Mugwanya, MBChB, MS

  University of Washington

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor, Global Health, Medicine, & Epidemiology

Study Record Dates

• First Submitted: May 15, 2016
• First Posted: May 18, 2016
• Study Start: January 1, 2015
• Primary Completion: May 1, 2015
• Study Completion: December 1, 2015
• Last Updated: September 21, 2021

Record last verified: 2021-09

Data Sharing

• IPD Sharing: Will share

Locations

KE (1); UG (1)