PrEP in Breastfeeding Study

NCT ID: NCT02776748

Last Updated: 2021-09-21

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 50 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-01-31
• Study Completion Date: 2015-12-31

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.

Conditions

HIV Pre-exposure Prophylaxis During Breastfeeding

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

FTC-TDF

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

Group Type: OTHER

FTC/TDF PrEP

Intervention Type: DRUG

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

Interventions

FTC/TDF PrEP

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

Intervention Type: DRUG

Other Intervention Names

Truvada PrEP

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)

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Bill and Melinda Gates Foundation

OTHER

Sponsor Role: collaborator

University of Washington

OTHER

Sponsor Role: lead

Responsible Party

Jared Baeten

Professor, Global Health, Medicine, & Epidemiology

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Jared M Baeten, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Washington

Kenneth K Mugwanya, MBChB, MS

Role: STUDY_DIRECTOR

University of Washington

Locations

Partners in Prevention-Thika

Thika, , Kenya

Partners in Prevention-Infectious Diseases Institute LTD

Kampala, , Uganda

Countries

Kenya; Uganda

References

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.

Reference Type: DERIVED

PMID: 27676257 (View on PubMed)

Other Identifiers

46363

Identifier Type: -

Identifier Source: org_study_id