Therapeutic Drug Monitoring to oPtimize ANtiretroviral regimeNs in HIV-infected Women Who wAnt to Breastfeed

Study Overview
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Brief Summary
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This is a prospective, multi-center, longitudinal, mother-infant pair, therapeutic drug monitoring study. The aim of this study is to determine concentrations of antiretroviral drugs in plasma and breastmilk in people living with HIV who chose to breastfeed while using antiretrovirals. At a planned hospital visit an extra maternal blood sample (1 to 2 per visit) and extra infant blood sample (1 per visit) will be collected, as well as a breastmilk sample (1 to 2 per visit). Ideally, sample collection will take place at least during the 1, 3 and 6 month post partum follow up visit. Measured concentrations will be used to calculate milk to plasma ratios, relative and absolute infant dosages.

Official Title
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Therapeutic Drug Monitoring to oPtimize ANtiretroviral regimeNs in HIV-infected Women Who wAnt to Breastfeed

Conditions
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HIV-1-infection

Intervention / Treatment
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* Diagnostic Test: Therapeutic drug monitoring in plasma of mother and child and in breastmilk


Participation Criteria
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Eligibility Criteria
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Inclusion criteria Patients of at least 18 years of age at the moment of screening Patients with HIV-1 as documented with positive HIV antibody test, HIV RNA of antigen test Patients breastfeeding their infant Patients using antiretrovirals for the treatment of HIV-1 with a marketing authorisation in Europe (table 1 in Appendix) Patients using current antiretrovirals for a minimum of 2 weeks to assure drug concentrations are in steady state Patients who are able and willing to sign an informed consent Exclusion Criteria: No exclusion criteria will be used at the screening for the trial.

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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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Antiretroviral drugs with marketing authorisation in Europe<br>This study includes subjects who already take antiretroviral drugs to treat HIV-1 with a marketing authorisation in Europe. These drugs already have a marketing authorisation and are prescribed by the treating physician of the subject. No adjustments to their treating regimen are made in order to participate in this study. All antiretrovirals with a marketing authorisation in Europe are eligible for inclusion in this study, but most subjects are expected to use a backbone of nucleoside reverse transcriptase inhibitors combined with either dolutegravir, raltegravir, darunavir or rilpivirine | Diagnostic Test: Therapeutic drug monitoring in plasma of mother and child and in breastmilk<br>* Measurement of drug concentration in plasma of mother and if possible of child and in breastmilk<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Breastmilk to maternal plasma ratio | Total concentration of antiretrovirals in breastmilk and plasma of the mother at a single time point to determine milk to plasma ratio. | 6 months post partum | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Absolute infant dose | (AID; µg/kg/day) = Cmilk * Vmilk | 6 months post partum | 
| Relative infant dose | Dosage infant (AID)/dosage mother | 6 months post partum | 
| Comparison of absolute infant dose to approved pediatric dose | For agents approved for pediatric use the absolute infant dose is compared to the approved pediatric dose (abacavir, emtricitabine, lamivudine, zidovudine, efavirenz, nevirapine, atazanavir, lopinavir, maraviroc, dolutegravir, raltegravir, ritonavir) | 6 months post partum | 
| Viral load in breastmilk | HIV RNA (copies/ml) | 6 months post partum | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Breastfeeding, Therapeutic drug monitoring, Breast milk to maternal plasma ratio, Antiretroviral therapy