Study on PhArmacokinetics of First liNe Antiretrovirals in Healthy Breastfeeding Volunteers

No to little data exists on penetration of antiretroviral drugs in breastmilk. Too high concentrations may lead to infant toxicity and too low concentrations may lead to development of resistance in case the infant inadvertently becomes infected with the virus.The aim of this trial is to determine the concentration of currently often used ARV (doravirine, raltegravir, bictegravir, tenofovir alafenamide, emtricitabine) in breast milk after administration of a single dose Study design: This is a single centre, single dose, open label, pharmacokinetic study in healthy volunteers.Study population: Adult, healthy volunteers at the end of their breastfeeding period Intervention: Administration of one dose of either doravirine (DOR) 100mg, raltegravir (RAL) 1200mg or a combination of tenofovir alafenamide 25mg, emtricitabine 200mg and bictegravir 50mg (BIC/FTC/TAF).Main study parameters/endpoints: Area under the plasma and milk concentration curve are used to calculate milk to plasma ratio.

Inclusion Criteria:At least 18 years of age at the moment of screeningAt least 10 days post partumAt the end of breastfeeding period; subject is able to produce breastmilk at least two times a day and is no longer feeding infant at start of studyAble and willing to sign an informed consentExclusion Criteria:Relevant co-medication or comorbidity that might interfere with drug absorption, distribution, metabolism or excretionInability to take drugs according to the instructions (i.e. with food)Presence of positive HIV screening or HIV RNAPresence of HBsAg or HBcAg without anti-HBsPresence of grade III/IV anaemia (i.e. Hb <4.6 mmol/L or <7.4 g/dL).Presence of hereditary forms of severe galactose intolerance, total lactase deficiency or glucose-galactose malabsorption