Therapeutic Drug Monitoring to oPtimize ANtiretroviral regimeNs in HIV-infected Women Who wAnt to Breastfeed (PANNA-B TDM)

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.

Study Overview

• Status: Completed
• Conditions: HIV-1-infection
• Intervention / Treatment: Diagnostic test: Therapeutic drug monitoring in plasma of mother and child and in breastmilk

• Study Type: Observational
• Enrollment (Actual): 16

Contacts and Locations

Study Locations

• Netherlands
  • Gelderland
    • Nijmegen, Gelderland, Netherlands, 6525GA
      • Radboudumc
  • North Holland
    • Amsterdam, North Holland, Netherlands
      • AmsterdamUMC
  • South Holland
    • Rotterdam, South Holland, Netherlands
      • ErasmusMC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

women living with HIV using antiretroviral medication who chose to breastfeed their child

Description

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.

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Only
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

Antiretroviral drugs with marketing authorisation in Europe; 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; Measurement of drug concentration in plasma of mother and if possible of child and in breastmilk

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse events in infant	As reported by the parents/caregivers and/or paediatrician	At every follow up visit (1,2,3,4,5,6 months post partum)
The place of the infant in population-specific percentile distributions of weight for age		At every follow up visit (1,2,3,4,5,6 months post partum)
HIV RNA in infant	(copies/ml)	At every follow up visit (1,2,3,4,5,6 months post partum)
Adverse events in mother	As reported by mother and/or treating physician	At every follow up visit (1,2,3,4,5,6 months post partum)
Kidney function	(estimated glomerular filtration rate - KDIGO)	At every follow up visit (1,2,3,4,5,6 months post partum)
Alanine aminotranferase in mother		At every follow up visit (1,2,3,4,5,6 months post partum)
Bilirubin in mother		At every follow up visit (1,2,3,4,5,6 months post partum)
Hemoglobin in mother		At every follow up visit (1,2,3,4,5,6 months post partum)
HIV RNA in mother	copies/ml	At every follow up visit (1,2,3,4,5,6 months post partum)

Collaborators and Investigators

• Sponsor: Radboud University Medical Center
• Collaborators: UMC Utrecht; Erasmus Medical Center; Amsterdam University Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2023
• Primary Completion (Actual): December 1, 2025
• Study Completion (Actual): December 1, 2025

Study Registration Dates

• First Submitted: November 9, 2022
• First Submitted That Met QC Criteria: November 29, 2022
• First Posted (Actual): December 8, 2022

Study Record Updates

• Last Update Posted (Estimated): December 9, 2025
• Last Update Submitted That Met QC Criteria: December 2, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Keywords: Therapeutic drug monitoring; Breastfeeding; Antiretroviral therapy; Breast milk to maternal plasma ratio
• Additional Relevant MeSH Terms: Behavior; Feeding Behavior; Breast Feeding; Diagnostic Techniques and Procedures; Diagnosis; Monitoring, Physiologic; Drug Monitoring
• Other Study ID Numbers: PANNA-B TDM

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No