Breastmilk Fed Infants of Mothers on Select DOI, HIV Infections, Lactating Women on Select DOI
Conditions
Brief summary
The purpose of this study is to characterize the pharmacokinetics (PK) of understudied drugs administered to lactating women, receiving antiretroviral drugs per SOC as prescribed by their healthcare provider, and their co-enrolled infants ≤180 days of age who receive maternal breastmilk.
Detailed description
Prospective, single-site, open label, PK and safety study. Co-enrollment of lactating women ≥18 years of age receiving drugs of interest (DOIs) per standard of care (SOC), as prescribed by their healthcare providers, and their infants who receive maternal breastmilk ≤180 days postpartum. To understand drug transfer into breastmilk and determine subsequent infant exposure, biological samples will be collected from lactating women (blood and breastmilk) and infants (blood). The opportunistic design of this study will allow for a minimal risk study, an expanded enrollment net, evaluation of antiretroviral drugs, and capitalization of procedures performed per SOC to maximize study efficiency and data collection and minimize potential risk to participants. The data collected through this initiative will provide valuable PK, dosing, and safety information for drugs in this vulnerable population in order to inform public health.
Interventions
DRUGDolutegravir
Dolutegravir will be administered in accordance with local SOC as prescribed by the lactating woman's healthcare provider. Not prescribed for this study.
DRUGLamivudine
Lamivudine will be administered in accordance with local SOC as prescribed by the lactating woman's healthcare provider. Not prescribed for this study.
DRUGEmtricitabine
Emtricitabine will be administered in accordance with local SOC as prescribed by the lactating woman's healthcare provider. Not prescribed for this study.
DRUGTenofovir Disoproxil Fumarate
Tenofovir Disoproxil Fumarate will be administered in accordance with local SOC as prescribed by the lactating woman's healthcare provider. Not prescribed for this study.
Sponsors
The Emmes Company, LLC
Duke University
Study design
Observational model
OTHER
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
Mothers/Infants: 1. Lactating women ≥18 years of age who are receiving at least one DOI per SOC who are ≤180 days postpartum, and their infants (≤180 days of age) who receive maternal breastmilk. 2. Informed consent, according to local IRB/REB/IEC guidelines, prior to any study-related procedures. 3. If the mother is receiving more than one DOI, the mother must have taken all DOIs that she is receiving concomitantly for the 6 doses prior to sample collection. 4. Mother participant is fluent in English or Setswana. 5. Willing to provide at least 1 of the below required samples between the co-enrolled mother/infant pair: * Maternal breastmilk * Infant blood
Exclusion criteria
Mothers/Infants: 1. Any concomitant condition which, in the opinion of the participant's healthcare provider, the site principal investigator (PI), a research nurse, or designee conducting the study, would preclude participation in the study. 2. Known pregnancy of mother during sample collection. 3. Mother has pumped any breastmilk at all in between the last 6 direct infant feedings prior to sample collection. 4. Infant was fed breastmilk in any manner besides nursing at mother's breast for any of the last 6 feedings prior to sample collection. 5. Previous enrollment on this study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Drug concentration in maternal plasma | Baseline | Drug concentration of a DOI in maternal plasma |
| Drug concentration in maternal breastmilk | Baseline | Drug concentration of a DOI in maternal breastmilk |
| Drug concentration in infant plasma | Baseline | Drug concentration of a DOI in infant plasma |
| Milk/Plasma ratio | Baseline | The drug exposure of selected DOIs will be evaluated using milk/plasma ratio |
| Estimated daily infant dose | Baseline | The drug exposure of selected DOIs will be evaluated using the estimated daily infant dose |
| Relative infant dose | Baseline | The drug exposure of selected DOIs will be evaluated using relative infant dose |
| Infant/maternal exposure ratio | Baseline | The drug exposure of selected DOIs will be evaluated using infant/maternal exposure ratio |
Other
| Measure | Time frame | Description |
|---|---|---|
| PK of selected DOIs in lactating women and breastmilk fed infants as measured by elimination Half-life (t1/2). | Baseline | Elimination Half-life (t1/2) |
| PK of selected DOIs in lactating women and breastmilk fed infants as measured by absorption rate constant (ka). | Baseline | Absorption rate constant (ka) |
| PK of selected DOIs in lactating women and breastmilk fed infants as measured by area under the curve (AUC). | Baseline | Area under the curve (AUC) |
| PK of selected DOIs in lactating women and breastmilk fed infants as measured by elimination rate constant (kel). | Baseline | Elimination rate constant (kel) |
| Correlation of PK parameters (drug concentration in maternal plasma) with maternal BMI | Baseline | Correlation of drug concentration of each DOI in maternal plasma with maternal BMI |
| Correlation of PK parameters (estimated daily infant dose) with maternal BMI | Baseline | Correlation of estimated daily infant dose of each DOI with maternal BMI |
| Correlation of PK parameters (relative infant dose) with maternal BMI | Baseline | Correlation of relative infant dose of each DOI with maternal BMI |
| Correlation of PK parameters (infant/maternal exposure ratio) with maternal BMI | Baseline | Correlation of infant/maternal exposure ratio for each DOI with maternal BMI |
| Safety ESIs for infants | Baseline | Will be collected from the medical record at the time of sample collection |
| PK of selected DOIs in lactating women and breastmilk fed infants as measured by maximum concentration (CMAX). | Baseline | Maximum concentration (CMAX) |
| Correlation of PK parameters (drug concentration in infant plasma) with maternal BMI | Baseline | Correlation of drug concentration of each DOI in infant plasma with maternal BMI |
| Correlation of PK parameters (milk/plasma ratio) with maternal BMI | Baseline | Correlation of milk/plasma ratio of each DOI with maternal BMI |
| PK of selected DOIs in lactating women and breastmilk fed infants as measured by time to reach maximum concentration (TMAX). | Baseline | Time to reach maximum concentration (TMAX) |
| Correlation of PK parameters (drug concentration in maternal breastmilk) with maternal BMI | Baseline | Correlation of drug concentration of each DOI in maternal breastmilk with maternal BMI |
| PK of selected DOIs in lactating women and breastmilk fed infants as measured by Clearance (CL) or apparent clearance (CL/F). | Baseline | Clearance (CL) or apparent clearance (CL/F) |
| PK of selected DOIs in lactating women and breastmilk fed infants as measured by volume of distribution (V) or apparent volume of distribution (V/F) | Baseline | Volume of distribution (V) or apparent volume of distribution (V/F) |
Countries
South Africa
Outcome results
None listed