PrEP-PP PK: PK of TAF and TDF for PrEP in Pregnant and Postpartum Women

Sponsor

University of California, Los Angeles (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT04937881

Collaborator

University of Cape Town (Other), Desmond Tutu HIV Foundation (Other), Gilead Sciences (Industry)

Enrollment

Location

Arms

Anticipated Duration (Months)

3.3

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Hiv	Drug: Tenofovir alafenamide Drug: Tenofovir Disoproxil Fumarate	Phase 3

Detailed Description

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

50 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

This phase III study is a randomised control trial (RCT) of 50 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.This phase III study is a randomised control trial (RCT) of 50 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.

Masking:

None (Open Label)

Primary Purpose:

Prevention

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

Anticipated Study Start Date :

Jun 1, 2022

Anticipated Primary Completion Date :

Mar 1, 2023

Anticipated Study Completion Date :

Sep 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: TAF arm Fixed dose combination of 200 mg emtricitabine (FTC) and 25 mg tenofovir alafenamide (TAF) delivered under direct observation for 8 weeks during pregnancy and 8 weeks in postpartum period	Drug: Tenofovir alafenamide Daily DOT fixed dose combination of 200 mg emtricitabine (FTC) and 300 mg tenofovir disoproxil fumarate (TDF) Other Names: TAF
Active Comparator: TDF arm Fixed dose combination of 200 mg emtricitabine (FTC) and 300 mg tenofovir disoproxil fumarate (TDF) delivered under direct observation for 8 weeks during pregnancy and 8 weeks in postpartum period	Drug: Tenofovir Disoproxil Fumarate Daily DOT fixed dose combination of 200 mg emtricitabine (FTC) and 25 mg tenofovir alafenamide (TAF) Other Names: TDF or Truvada

Arm

Intervention/Treatment

Experimental: TAF arm

Fixed dose combination of 200 mg emtricitabine (FTC) and 25 mg tenofovir alafenamide (TAF) delivered under direct observation for 8 weeks during pregnancy and 8 weeks in postpartum period

Drug: Tenofovir alafenamide

Daily DOT fixed dose combination of 200 mg emtricitabine (FTC) and 300 mg tenofovir disoproxil fumarate (TDF)

Other Names:

TAF

Active Comparator: TDF arm

Fixed dose combination of 200 mg emtricitabine (FTC) and 300 mg tenofovir disoproxil fumarate (TDF) delivered under direct observation for 8 weeks during pregnancy and 8 weeks in postpartum period

Drug: Tenofovir Disoproxil Fumarate

Daily DOT fixed dose combination of 200 mg emtricitabine (FTC) and 25 mg tenofovir alafenamide (TAF)

Other Names:

TDF or Truvada

Outcome Measures

Primary Outcome Measures

Tenofovir diphosphate (TDF-DP) concentrations in plasma and interceullalar levels in pregnant and pospartum women on daily PrEP [8 weeks after directly observed treatment]
Plasma and intracellular levels of tenofovir and TFV-DP in the PrEP setting, comparing the drugs TAF to TDF

Secondary Outcome Measures

Tenofovir diphosphate (TDF-DP) concentrations in plasma and interceullalar levels comparing pregnancy against postpartum women [8 weeks after directly observed treatment]
Plasma and intracellular levels of tenofovir and plasma TDF-DP in antenatal and postpartum groups intra-individual comparisons.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

18 years old
confirmed HIV-negative (confirmed with a 4th generation antigen HIV test) at time of study entry
intend on giving birth in the MOU facility
confirmed to be 14-24 weeks pregnant
without psychiatric or medical contraindications to PrEP
estimated creatinine clearance (CrCI) >60mL/min
resides close to clinic (<10km)
has a smart phone that can take video footage (with data bundle from study)
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:

Concurrent enrolment in another HIV-1 vaccine or prevention trial
History of renal disease
Current clinical diagnosis of hypertension
Exhibiting psychotic symptoms
Currently or history of taking an anti-psychotic medication
Positive Hepatitis B surface antigen (HBsAg) test on screening
History of bone fracture not related to trauma
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
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.