Study Objectives

Primary Objective

1. To describe the pharmacokinetic parameters during pregnancy of selected ARV drugs currently used in the clinical care of HIV-infected pregnant women, and to compare these parameters to a) historical pharmacokinetic data from non-pregnant women and b) postpartum pharmacokinetic data from thEesame women in the study cohorts.
2. To describe the pharmacokinetic parameters during pregnancy and postpartum of selected ARV drugs (efavirenz, lopinavir/ritonavir) and first line TB drugs when co-administered as part of clinical care of HIV-infected pregnant women and of first line TB drugs when used in HIV-uninfected pregnant women.
3. To describe the pharmacokinetic parameters during pregnancy and postpartum of second line TB drugs administered as part of clinical care to HIV-infected and HIV-uninfected pregnant women.
4. To describe the pharmacokinetic parameters of ARV drugs in postpartum women before and after starting hormonal contraceptives.
5. To describe the concentrations of ethinyl estradiol, etonogestrel and other progestins in women using hormonal contraceptives and selected ARV drugs as compared to historical controls not using those ARV drugs.

Secondary Objectives

• To compare ARV and TB drug concentrations in plasma from cord blood with those in maternal plasma at the time of delivery.
• To assess plasma protein binding of highly bound ARV drugs during pregnancy and postpartum.
• To assess ARV concentrations and HIV RNA/DNA concentrations in vaginal secretions among pregnant and postpartum and compare to simultaneous plasma concentrations.
• To explore genetic sources for variability in ARV and TB drug exposure in pregnant women and their infants.
• To describe maternal and infant safety and clinical outcomes.
• To describe the neonatal elimination of selected ARV and TB drugs acquired across the placenta after maternal dosing during pregnancy.
• To describe pharmacokinetics of ARV drug combinations in HIV-infected women on second line TB treatment.

Study Design: Phase IV, prospective pharmacokinetic (PK) study

Study Population: Each study arm will enroll a minimum of 12 women and have a target enrollment of 25 women with evaluable 3rd trimester PK data for antiretroviral (ARV) and tuberculosis (TB) arms, or evaluable postpartum PK data for hormonal contraceptive arms. Women who do not have evaluable PK data will be replaced. Enrollment may be restricted to the second trimester and/or increased above 25 so that evaluable 2nd trimester PK data are obtained from at least 12 women. Enrollment may also be increased above 25 to obtain additional second line TB drug data or infant washout PK data.

Botswana sites enrolled 2 participants who have successfully completed study follow up. The study had a target of 15 participants across both sites (Gaborone and Molepolole). The study closed to accrual on December 2019. There was a challenge of finding pregnant women who have TB and are HIV infected.

Study Duration: HIV-infected pregnant women without tuberculosis (TB) will be followed for 6 –12 weeks after delivery with the exception of women on DRV/r who will be followed for 2 – 3 weeks after delivery. HIV-infected and non-infected women receiving TB treatment (first or second line) will be followed for 2 – 8 weeks after delivery. Postpartum women will be followed until 6 – 7 weeks after the initiation of hormonal contraceptives. Infants will be followed for 16 – 24 weeks of life.

Study Status: Closed for Accrual

Sponsor: Division of AIDS, the National Institute of Allergy and Infectious Diseases.