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

Hiv Clinical Trial

— PrEP-PP PK  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04937881
• Other study ID #: CO-US-412-6091
• Status: Completed
• Phase: Phase 3
• Start date: June 13, 2022
• Est. completion date: September 1, 2023

Study information

• Verified date: December 2023
• Source: University of California, Los Angeles
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 50
• Est. completion date: September 1, 2023
• Est. primary completion date: April 17, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Hiv

Intervention

Drug:
• Tenofovir alafenamide
Daily DOT fixed dose combination of 200 mg emtricitabine (FTC) and 300 mg tenofovir disoproxil fumarate (TDF)
• Tenofovir Disoproxil Fumarate
Daily DOT fixed dose combination of 200 mg emtricitabine (FTC) and 25 mg tenofovir alafenamide (TAF)

Locations

Country	Name	City	State
South Africa	Gugulethu Midwife Obstetric Unit	Cape Town

Sponsors (4)

Lead Sponsor	Collaborator
University of California, Los Angeles	Desmond Tutu HIV Foundation, Gilead Sciences, University of Cape Town

Country where clinical trial is conducted

South Africa, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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