Pharmacy and Poisons Board
Protocol No: ECCT/14/09/03 Date of Protocol: 08-08-2014
Study Title:

An open-label, short-duration, repeat-dose study of breast milk excretion and infant absorption of daily oral Tenofovir Disoproxil Fumarate/Emtricitabine when used by HIV-1 uninfected lactating women 
Study Objectives:

 

To quantify the steady state concentrations of tenofovir (TFV) and emtricitabine (FTC) in infant plasma after FTC/TDF PrEP exposure through maternal breast milk.
Laymans Summary:

Other research studies have found that pregnant women who take the Truvada® medication do not have increased risks of serious problems with their pregnancy and their babies do not have serious birth defects. More research studies in HIV-uninfected women who are taking Truvada® medication during pregnancy and breast feeding are needed. The purpose of this study is to find out more about using Truvada® during breast feeding. Specifically, this research will study the amount of Truvada® drugs that are transferred into breast milk and then absorbed by the nursing baby when Truvada® is used by breast feeding women as PrEP.
Abstract of Study:

Pre-exposure prophylaxis (PrEP) with tenofovir disoproxil fumarate (TDF) alone or in combination with emtricitabine (FTC/TDF) reduces the risk of HIV-1 acquisition in high-risk HIV-1-uninfected adults.1-4  Clinical trials have demonstrated protection efficacies of 44-75% in randomized comparisons to placebo and ~90% in case-control analyses of participants with high PrEP adherence. On the basis of these data, the US Food and Drug Administration (FDA) approved the use of FTC/TDF for PrEP in July 20125. The World Health Organization also issued guidance on oral PrEP, specifically for heterosexual HIV-1 serodiscordant couples and men and transgender women who have sex with men, regarding use in the context of demonstration projects to garner additional information to facilitate policies about PrEP implementation6. In addition, the US Centers for Disease Control and Prevention (CDC) issued interim guidance for clinicians considering using PrEP for prevention of HIV-1 infection in high-risk heterosexually active adults7, and identified the need for data on infant safety during pregnancy and postpartum breastfeeding for heterosexual women using FTC/TDF to prevent acquisition of HIV-1. The risk of HIV-1 acquisition is increased two-fold in women during pregnancy and the early post-partum period8, and thus PrEP could be an important strategy to reduce risk of HIV-1, if demonstrated to be safe.  Accordingly, it is important to assess whether FTC/TDF when used as PrEP by lactating mothers is excreted into breast milk and absorbed by the nursing infant in biologically significant concentrations. Determining the concentration of FTC/TDF infants are exposed to and subsequently absorbed via breast milk when taken daily as PrEP by lactating women is needed to evaluate the benefits and risks of maternal FTC/TDF PrEP use during lactation. Specially, the concentration of FTC and TDF excreted into and absorbed by nursing infants via breast milk of lactating women using FTC/TDF PrEP for HIV-1 prevention has not been studied. This protocol describes an  interventional, open-label, single-arm, repeat-dose study among heterosexual HIV-1 uninfected lactating women to determine the magnitude and extent of infant exposure to daily FTC/TDF via maternal breast milk when taken over one week as PrEP by lactating women. 

Design:   Interventional, open-label, single-arm, repeat-dose, pharmacokinetic study Up to 10 days of follow-up per mother-infant pairs

Population:  HIV-1 uninfected lactating mother-infant pairs

Study Site:  Thika, Kenya and Kampala, Uganda Partners PrEP Study sites

Approach:  We will enroll up to 50 mother-infant pairs to characterize infant drug absorption for infant ages 0-24 weeks postpartum. We will conduct quantitative analyses to describe the magnitude and extent of infant exposure to FTC/TDF PrEP through breast milk when used by lactating women.

Specific Aim:

To quantify the steady state concentrations of tenofovir (TFV) and emtricitabine (FTC) in infant plasma after FTC/TDF PrEP exposure through maternal breast milk.

Decisions about the safety of breast feeding during maternal ingestion of drugs require knowledge of the amount of drug which might be present in breast milk. Understanding the concentration of FTC/TDF infants are exposed to and subsequently absorbed via breast milk when taken as PrEP by lactating women is needed to permit a thorough evaluation of the benefits and risks of maternal FTC/TDF PrEP use during lactation. We will measure infant plasma, maternal plasma, and breast milk FTC and TFV concentrations in an open-label, repeat dose study of daily FTC/TDF PrEP among HIV-1-uninfected lactating mother-infant pairs.

The primary outcomes of this study will be the steady state infant plasma FTC and TFV levels, infant plasma to maternal breast milk FTC and TFV concentration ratios, and maternal breast-milk to plasma FTC and TFV concentration ratio. A single infant plasma sample will be collected after the maternal 7th PrEP dose. Maternal plasma and breast-milk samples each will be collected for trough and peak levels immediately before administration of the 7th and 10th doses and 1-2 hours after the 7th and 10th doses, respectively.