Pharmacokinetics and Safety of Antiretroviral Drugs in Lactating Women and Breastmilk Fed Infants

Study Overview
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Brief Summary
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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
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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.

Official Title
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Pharmacokinetics and Safety of Antiretroviral Drugs in Lactating Women and Breastmilk Fed Infants

Conditions
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Lactating Women on Select DOI, Breastmilk Fed Infants of Mothers on Select DOI, HIV Infections

Intervention / Treatment
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* Drug: Dolutegravir
* Drug: Efavirenz
* Drug: Emtricitabine
* Drug: Tenofovir Disoproxil Fumarate


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria Mothers/Infants: 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. Informed consent, according to local IRB/REB/IEC guidelines, prior to any study-related procedures. Mother must have taken all DOIs concomitantly for the 6 doses prior to sample collection. Mother participant is fluent in English or Setswana. 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: 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. Known pregnancy of mother during sample collection. Mother has pumped any breastmilk at all in between the last 6 direct infant feedings prior to sample collection. Infant was fed breastmilk in any manner besides nursing at mother's breast for any of the last 6 feedings prior to sample collection. Previous enrollment on this study.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Drug of Interest<br>Lactating moms receiving one or more antiretroviral drugs and their breastmilk fed infants per standard of care. | Drug: Dolutegravir<br>* Dolutegravir will be administered in accordance with local SOC as prescribed by the lactating woman's healthcare provider. Not prescribed for this study.<br>* Other names: DTG;Drug: Efavirenz<br>* Efavirenz will be administered in accordance with local SOC as prescribed by the lactating woman's healthcare provider. Not prescribed for this study.<br>* Other names: EFV;Drug: Emtricitabine<br>* Emtricitabine will be administered in accordance with local SOC as prescribed by the lactating woman's healthcare provider. Not prescribed for this study.<br>* Other names: FTC;Drug: Tenofovir Disoproxil Fumarate<br>* 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.<br>* Other names: TDF;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Drug concentration in maternal plasma | Drug concentration of a DOI in maternal plasma | Baseline | 
| Drug concentration in maternal breastmilk | Drug concentration of a DOI in maternal breastmilk | Baseline | 
| Drug concentration in infant plasma | Drug concentration of a DOI in infant plasma | Baseline | 
| Milk/Plasma ratio | The drug exposure of selected DOIs will be evaluated using milk/plasma ratio | Baseline | 
| Estimated daily infant dose | The drug exposure of selected DOIs will be evaluated using the estimated daily infant dose | Baseline | 
| Relative infant dose | The drug exposure of selected DOIs will be evaluated using relative infant dose | Baseline | 
| Infant/maternal exposure ratio | The drug exposure of selected DOIs will be evaluated using infant/maternal exposure ratio | Baseline | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety ESIs | Safety ESIs for infants collected from the medical record at the time of sample collection | Baseline |