Title: Pharmacokinetic Properties of Antiretroviral and Anti-Tuberculosis Drugs during Pregnancy and Postpartum.

Lay Title: Effect of HIV and TB medicines when taken during pregnancy and after delivery.

What is theproblem/background?

Clinical trials studying the breakdown, absorption and excretion of antiretroviral (ARV) and tuberculosis (TB)medication during pregnancy and/or postpartum, are limited.Obtaining data on how pregnancy affects drug exposure isimportant so that safe and effective doses of ARVs and anti- tuberculin medications for pregnant women can be prescribed.

What questionsarewetryingtoanswer?

The study seeks to establish the amounts of certain ARVs and TB medications in women taking this medications during pregnancy and postpartum period and also at how much of these medications are transferred from mother to infants during breastfeeding. The aim is to obtain data on how pregnancy affects breakdown and absorption of these medications thus ensure safe and effective use of these medicines during pregnancy and breastfeeding.

Where is the study taking place,how many people does it involve and how are they selected?

The study will take place in multiple sites, Kericho being one of them. The study will enroll a total of 325 participants across all sites into 5 components. A total of 30 participants (mother-infant pairs) will be enrolled in Kericho, 20 into component 3 and 10 into component 5. The participants will be selected by active identification and referral from surrounding health facilities.

What does the study involve for those who are in it?

Participants will be enrolled while on selected ARVs and anti-TB medications. They will continue taking these medications while on study. Blood samples will be taken during pregnancy and after they deliver. Blood samples will also be taken from infants of mothers enrolled during pregnancy.

Whatarethebenefitsandrisks/costsofthestudyforthoseinvolved?

The mothers and infants in the study will benefit from provision of ancillary medical care from entry to completion of the study at no cost to the them. The risks of this study are mainly due to blood collection which may cause pain, bruising, swelling, or fainting. There is a very small chance of infection where the needle is inserted. It may be uncomfortable to express breast milk. Blood collection from infants will be done by heel stick, which may cause some discomfort, bleeding or bruising at the site of the heel stick. There is also risk of breach of confidentiality.

How will the study benefit society?

Information learned from this study may be of benefit to participants and others in the future.

When does the study start and finish?

The study is expected start in the first quarter of 2021 and take approximately 5 years to end in the year 2026.

Tuberculosis (TB) and Human Immunodeficiency Virus (HIV) are important health problems worldwide with TB remaining one of the greatest threats to public health and a leading cause of death from an infectious pathogen. It is also known that the HIV epidemic has fueled the resurgence of TB leading to dramatic increase in TB infections in low and middle income countries. The development of appropriate antiretroviral (ARV) and TB drug regimens in pregnant and postpartum women is critical to providing optimal care to women living with human immunodeficiency virus (HIV) and/or TB, and their infants to prevent disease progression There are limited studies looking at pharmacokinetics of ARVs and TB drugs during pregnancy and post-partum.

The study will enroll women who are already on select ARVs and TB medications under study with the aim of obtaining pharmacokinetic(PK) parameters of these medications when used alone or in combination during pregnancy and post-partum in women living with and without HIV by drawing PK samples at various time points. Breastmilk will also be collected from some participants during the postpartum period. The study is comprised of 5 components based on the ARVs or TB medications the participants are receiving. Kericho site will enroll into components 3 and 5. Component 3 are pregnant women living with HIV receiving ARVs and first line TB treatment and their infants while component 5 are postpartum women living with HIV breastfeeding while receiving ARVs and their infants.

Data obtained from this study will establish the effect of pregnancy on drug exposure and also the kinetics of transmission ARVs and TB treatment drugs from mother to infant and thus inform guidelines on appropriate ARVs and TB medications during pregnancy and lactation.

Kericho site will enroll up to 30 mother infant pairs intothe study, 10 mother infant pairs will be enrolled into component 5 while 20 mother infant pairs will be enrolled into component 3. Participants who will be enrolled into component 3 will be enrolled in the second or third trimester and be in the study up to 24 weeks after delivery. Those in component 5 will be enrolled immediately after delivery and followed up for 24 weeks.