Clinical trial NCT04937881: PK of TAF and TDF for PrEP in Pregnant and Postpartum Women
Official title: Comparison of Pharmacokinetics of Tenofovir Alafenamide (TAF) With Tenofovir Disoproxil (TDF) in Pregnant and Postpartum Women and Their Infants in PrEP-PP Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Hiv
Keywords: pre-exposure prophylaxis
PrEP
pregnancy
postpartum
HIV prevention
pharmacokinetics
TAF
TDF
Lead sponsor: University of California, Los Angeles
Sponsor class: OTHER
Collaborators: name: University of Cape Town
name: Desmond Tutu HIV Foundation
name: Gilead Sciences
First posted: 2021-06-24
Enrollment: 39
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: This phase III study is a randomised control trial (RCT) of up to 60 pregnant women who will be recruited at first antenatal visit (ANC) from the Gugulethu Midwife and Obstetrics Unit.

Participants will be randomized into the TDF vs TAF arm:

TDF Arm: Women will receive a fixed dose combination of 200 mg emtricitabine (FTC) and 300 mg tenofovir disoproxil fumarate (TDF) administered once daily under direct observation for 8 weeks during pregnancy and again for 8 weeks in postpartum period

TAF Arm: Fixed dose combination of 200 mg emtricitabine (FTC) and 25 mg tenofovir alafenamide (TAF) administered once daily under direct observation for 8 weeks during pregnancy and again for 8 weeks in postpartum period Women will provide their own controls, providing pregnant and postpartum samples.
Primary purpose: PREVENTION

Brief summary: This study will establish benchmarks of TFV-DP concentrations as measures of adherence following daily dosing with Tenofovir Alafenamide (TAF) compared with Tenofovir Disoproxil Fumarate (TDF) during pregnancy and postpartum. Study Investigators will recruit from an ongoing observational cohort study in Cape Town, South Africa, PrEP-PP (recruitment ongoing through July, 2021; NIMH R01MH116771; PI Coates \& Myer). Findings form this PK sub-study will be used to inform future PrEP in pregnancy and postpartum studies and develop benchmarks of the relative PK between TDF and TAF.

Detailed description: This study will establish benchmarks of TFV-DP concentrations as measures of adherence following daily dosing with Tenofovir Alafenamide (TAF) compared with Tenofovir Disoproxil Fumarate (TDF) during pregnancy and postpartum. Study Investigators will recruit from an ongoing observational cohort study in Cape Town, South Africa, PrEP-PP (recruitment ongoing through July, 2021; NIMH R01MH116771; PI Coates \& Myer). Findings form this PK sub-study will be used to inform future PrEP in pregnancy and postpartum studies and develop benchmarks of the relative PK between TDF and TAF.

Study aims. (1) To establish benchmarks of TFV-DP concentrations as measures of adherence following daily dosing with TAF vs TDF in pregnancy and again in postpartum; (2) To compare the difference of TFV-DP within TDF and TAF for pregnancy vs. postpartum, and to establish adherence benchmarks of levels of TFV in breastmilk in postpartum women and compare with TDF sample.

The study will take place in an urban township in Cape Town (Gugulethu) with high HIV incidence that spans the different socioeconomic, cultural, and ethnic groups in South Africa. We selected this community because of the high HIV prevalence there in pregnant and breastfeeding women, and because of the high number of mothers visiting every month for ANC and labour/delivery.

Eligibility criteria: Inclusion Criteria:

1. \>18 years old
2. confirmed HIV-negative (confirmed with a 4th generation antigen HIV test) at time of study entry
3. intend on giving birth in the MOU facility
4. confirmed to be 14-24 weeks pregnant
5. without psychiatric or medical contraindications to PrEP
6. estimated creatinine clearance (CrCI) \>60mL/min
7. resides close to clinic (\<10km)
8. has a smart phone that can take video footage (with data bundle from study)
9. agrees to provide video phone footage of taking a pill a day for 8 weeks during pregnancy and again for 8 weeks in postpartum period

Exclusion Criteria:

Individuals not meeting the above criteria or meeting any of the following criteria will be excluded:

1. Concurrent enrolment in another HIV-1 vaccine or prevention trial
2. History of renal disease
3. Current clinical diagnosis of hypertension
4. Exhibiting psychotic symptoms
5. Currently or history of taking an anti-psychotic medication
6. Positive Hepatitis B surface antigen (HBsAg) test on screening
7. History of bone fracture not related to trauma
8. Any other medical, psychiatric or social condition which in the opinion of the investigators would affect the ability to consent and/or participate in the study
9. Any maternal or fetal complication, obstetric or medical, detected during routine care or study procedures that requires referral of pregnant or postpartum women/infants to secondary or tertiary obstetric or medical care.

Primary outcomes:
measure: Tenofovir Diphosphate (TFV-DP) Levels in Plasma and Intracellular Levels in Pregnant Women on Daily PrEP
timeFrame: 8 week period during Pregnancy
measure: Tenofovir Diphosphate (TFV-DP) Levels in Plasma and Intracellular Levels in Postpartum Women on Daily PrEP
timeFrame: 8 week period during Postpartum (up to 1 year from baseline pregnancy visit)
Secondary outcomes:
measure: Tenofovir Diphosphate (TFV-DP) Concentrations in Plasma and Intracellular Levels Comparing Pregnancy Against Postpartum Women
timeFrame: Pregnancy (TVF-DP measures via DBS collected weekly, reported 8 weeks after start of pregnancy observation); Postpartum (TVF-DP measures via DBS collected weekly, reported 8 weeks after start of postpartum observation, up to 1 year from baseline).
Other outcomes:
Locations:
city: Cape Town
country: South Africa
facility: Gugulethu Midwife Obstetric Unit
Study officials:
affiliation: UCT
name: Landon Myer, MD
role: PRINCIPAL_INVESTIGATOR
References: