PK of TAF and TDF for PrEP in Pregnant and Postpartum Women

Study Overview
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Brief Summary
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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
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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.

Official Title
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Comparison of Pharmacokinetics of Tenofovir Alafenamide (TAF) With Tenofovir Disoproxil (TDF) in Pregnant and Postpartum Women and Their Infants in PrEP-PP Study

Conditions
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Hiv

Intervention / Treatment
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* Drug: Tenofovir alafenamide
* Drug: Tenofovir Disoproxil Fumarate


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional 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.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TAF arm<br>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<br>* Daily DOT fixed dose combination of 200 mg emtricitabine (FTC) and 300 mg tenofovir disoproxil fumarate (TDF)<br>* Other names: TAF;|
| Active Comparator: TDF arm<br>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<br>* Daily DOT fixed dose combination of 200 mg emtricitabine (FTC) and 25 mg tenofovir alafenamide (TAF)<br>* Other names: TDF or Truvada;|

What is the study measuring?
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Primary Outcome Measures

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

Secondary Outcome Measures

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

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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pre-exposure prophylaxis, PrEP, pregnancy, postpartum, HIV prevention, pharmacokinetics, TAF, TDF