Table 1 Eligibility studies actively involved in the recruitment of pregnant and breastfeeding women at the IDI clinic in Uganda

Pharmacokinetics of drugs used to treat drug-sensitive tuberculosis in breastfeeding mother-infant pairs [15].

Observational pharmacokinetic study

To define the transfer of isoniazid, rifampicin, pyrazinamide, and ethambutol to a breastfed infant.

To determine the AUC, clearance, and volume of distribution of these drugs.

• Maternal blood and breastmilk collected at 2, 4, 6, 8, and ideally* 24 h post-dose.

• Infant blood sample collected at maternal trough (pre-dose) and anytime for 3–8 h post maternal dose.

20 mother-infant pairs

2021-Ongoing

Pharmacokinetics of drugs used to treat uncomplicated malaria in breastfeeding mother-infant pairs [14].

Observational pharmacokinetic study

To define the transfer of lumefantrine and its active metabolite, dibutyl-lumefantrine from mother to breast-fed infant.

To determine the clearance, AUC, and volume of distribution of lumefantrine and disbutyl-lumefantrine

• Maternal blood and breastmilk were collected at pre-dose 2-, 4-, 6- and 8- hours post-dose.

• Breastmilk collected at pre-dose 2, 4, 6, 8 h post-dose.

• In addition, sparse sampling after the third or fourth dose and lastly at 5, 7, and up to 14 days after the first dose.

• Infant blood (heel prick) was collected at the maternal trough and at a random time point over the 8-hour pharmacokinetic sampling.

30 mother-infant pairs

2022-Ongoing

Investigation of the pharmacokinetics of atazanavir in pregnant women, individuals at extremes of BMI, children, and adolescents. An observational study nested within the virtual consortium. (NCT03923231)

Observational

study

To describe the pharmacokinetic parameters of atazanavir currently used in the clinical care of pregnant women living with HIV and postpartum women, children and adolescents, and individuals with obesity or malnutrition.

To compare these parameters to those observed in non-pregnant adults living with HIV on second-line ART who enter a dose escalation study of ATV/r + RIF

• 20 sparse pharmacokinetic profiles in each of the following groups (pregnant, child < 5, child 6–11, adolescent 12–18, obese (BMI > 30 Kg/m²), malnourished (BMI < 18.5 Kg/m²). Everyone contributes 4 samples per PK visit.

• Blood Sampling at pre-dose, 2, 4, and 6* hours post-dose

*Given the potential challenges of sampling in lactating mother-infant pairs, the 6-hour time point was optional

20–40

Pregnant women and children less than 5 years old.

2017–2019

Understanding the pharmacokinetics of antiretroviral drugs in breastfeeding mother-infant pairs [19].

Observational pharmacokinetic study

To determine the AUC, clearance, and volume of distribution of (efavirenz/tenofovir + Emtricitabine or lamivudine) in maternal plasma and breast milk, and upper and lower estimates of concentration in breastfed infants.

To examine the impact of covariates on maternal and infant drug exposure

Intensive sampling schedule on 40 mother-infant pairs

Maternal sampling:

• Morning dose: 0, 1, 2, 4 and 8 h postdose

• Evening dose: 12, 16- and 20 h post-dose

Infant Sampling: pre-feed at the maternal trough; 2 h after a mandated feed at 2 h post-dose. sample taken only in the infants of mothers who take their drugs in the morning), at a later randomized time point (5–8 h).

Sparse sampling schedule of single time point maternal plasma, breastmilk, and infant blood samples on 160 mother-infant pairs.

200 mothers

infant pairs

2016–2018

Development and validation of an assay for quantitation of antiretrovirals in human breastmilk [19].

Observational pharmacokinetic study – pilot feasibility and acceptability, together with assay development

To determine the AUC, clearance, and volume of distribution of (efavirenz/tenofovir + Emtricitabine or lamivudine) in maternal plasma and breast milk, and upper and lower estimates of concentration in breastfed infants

Maternal sampling:

• Morning dose: 0, 1-, 2-, 4- and 8 h post-dose

• Evening dose: 12, 16- and 20 h post-dose

Infant Sampling: pre-feed at the maternal trough; 2 h after a mandated feed at 2 h post-dose. the sample was taken only in the infants of mothers who take their drugs in the morning), at a later randomized time point (5–8 h).

30 mother-infant pairs

2014–2016