HivPhase 3PrEP-PP PKNCT04937881

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

A Phase 3 study testing Tenofovir alafenamide and Tenofovir Disoproxil Fumarate in people with Hiv, run by University of California, Los Angeles at 1 site in South Africa.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

Search all trials

Trial summary

Who is it for?: Ages 18 years and older, women onlyHealthy volunteers can take part
Conditions the study is for: Hiv
What is being tested?: Tenofovir alafenamide and Tenofovir Disoproxil Fumarate
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 39 participants
Where: 1 siteSouth Africa
Study dates: 13 Jun 2022to 1 Sep 2023
Phase: Phase 3
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
Women only
Healthy volunteers accepted
Adult, Older adult

Who may be able to join

>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

Show all 9Show fewer

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

Who cannot join

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

Show all 10Show fewer

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.

Trial locations and contacts

1 site in 1 country.

South Africa1 site

Gugulethu Midwife Obstetric Unit
Cape Town

Other trials in South Africa

About this study

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

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.

Read the 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.

Conditions: Hiv
Being tested: Tenofovir alafenamide, Tenofovir Disoproxil Fumarate
Keywords: pre-exposure prophylaxis, PrEP, pregnancy, postpartum, HIV prevention, pharmacokinetics, TAF, TDF
Medical subject headings: Acquired Immunodeficiency Syndrome

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Tenofovir alafenamideDrug
Also called TAF
Daily DOT fixed dose combination of 200 mg emtricitabine (FTC) and 25 mg tenofovir alafenamide (TAF)
Tenofovir Disoproxil FumarateDrug
Also called TDF or Truvada
Daily DOT fixed dose combination of 200 mg emtricitabine (FTC) and 300 mg tenofovir disoproxil fumarate (TDF)

Study groups in NCT04937881
Study group	Role	What they receive
TAF arm	Experimental	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 Receives: Drug: Tenofovir alafenamide
TDF arm	Active comparator	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 Receives: Drug: Tenofovir Disoproxil Fumarate

What is being measured

The primary outcome is the main question the study is designed to answer.

Tenofovir Diphosphate (TFV-DP) Levels in Plasma and Intracellular Levels in Pregnant Women on Daily PrEP
Levels of TFV-DP (geometric mean), comparing the drugs TAF to TDF, observed in pregnancy.
Note: Observation of daily PrEP dosing spanned 16 weeks in total, including 8 weeks during pregnancy and 8 weeks in postpartum. Once participants had completed their 8 weeks of in-pregnancy observation, observation of therapy was paused until they entered the postpartum phase.
Measured: 8 week period during Pregnancy
Tenofovir Diphosphate (TFV-DP) Levels in Plasma and Intracellular Levels in Postpartum Women on Daily PrEP
Levels of TFV-DP (geometric mean), comparing the drugs TAF to TDF, observed in postpartum period.
Note: Observation of daily PrEP dosing spanned 16 weeks in total, including 8 weeks during pregnancy and 8 weeks in postpartum. Once participants had completed their 8 weeks of in-pregnancy observation, observation of therapy was paused until they entered the postpartum phase.
Measured: 8 week period during Postpartum (up to 1 year from baseline pregnancy visit)

Secondary outcomes (1)

Tenofovir Diphosphate (TFV-DP) Concentrations in Plasma and Intracellular Levels Comparing Pregnancy Against Postpartum Women
Plasma and intracellular concentrations of tenofovir and plasma TFV-DP in antenatal and postpartum groups intra-individual comparisons.
Note: TFV-DP measures were obtained by DBS once a week during periods of observation. Observation of daily PrEP dosing spanned 16 weeks in total, including 8 weeks during pregnancy and 8 weeks in postpartum. Once participants had completed their 8 weeks of in-pregnancy observation, observation of therapy was paused until they entered the postpartum phase.
Measured: 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).

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

13 Jun 20221 Sep 2023

First posted24 Jun 2021
Study start13 Jun 2022
Primary completion17 Apr 2023
Study completion1 Sep 2023

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for HivStudies of the same condition, open and under way.
More trials run by University of California, Los AngelesThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 3
Primary purpose: Prevention
Allocation: Randomised
Intervention model: Parallel groups
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.
Masking: None (open label)
Enrolment: 39 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT04937881
Sponsor's protocol ID: CO-US-412-6091
Acronym: PrEP-PP PK
Status last verified: Aug 2024
First submitted: 8 Jun 2021
Last updated: 3 Sep 2024
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

Not yet recruiting
HealthMpowerment Korea: Pilot Testing the Cultural Adaptation of a Digital HIV Intervention for Men Who Have Sex With Men in South Korea
HIV Infections, HIV Prevention and Care
Not yet recruiting
Prescribe to Prevent HIV: A Hybrid Trial Helping Addiction Clinics Prevent HIV & Infections Through Safer Drug Use Support
People Who Use Opioids/People With Opioid Use Disorder (OUD)
Recruiting
Evaluating the Impact of Using the B-OK Bottles for HIV and ART Literacy in South Africa
HIV, HIV Treatment
Recruiting
Trial Phase: Syndemic Adapted Medly Uganda
Mental Health
RecruitingObservational study
Olfactory Function and Model-Based Behavior in People Living With HIV and SUD
HIV, Substance Use Disorder

All Hiv trials

Study at a glance

From the registry record, last updated by the sponsor on 3 Sep 2024. Recruitment status is as the sponsor reported it: confirm with the study team.

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
ClinicalTrials.gov ID: NCT04937881
Acronym / sponsor ID: PrEP-PP PK / CO-US-412-6091
Conditions: Hiv
Keywords: pre-exposure prophylaxis, PrEP, pregnancy, postpartum, HIV prevention, pharmacokinetics, TAF, TDF
Phase: Phase 3
Study type: Interventional
Recruitment status: Completed
Enrolment: 39 participants (actual)
Lead sponsor: University of California, Los AngelesUniversity, hospital or other
Collaborators: University of Cape Town, Desmond Tutu HIV Foundation, Gilead Sciences
Study start: 13 Jun 2022 (actual)
Primary completion: 17 Apr 2023 (actual)
Study completion: 1 Sep 2023 (actual)
First posted: 24 Jun 2021 (actual)
Results: Posted 3 Sep 2024

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Prevention
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 2
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.

Arm	Type	Receives
TAF arm	Experimental	Drug: Tenofovir alafenamideFixed 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
TDF arm	Active comparator	Drug: Tenofovir Disoproxil FumarateFixed 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

Who may qualify

Ages: 18 years and older
Sex: Female only
Healthy volunteers: Accepted
Age groups: Adult, Older adult

Key inclusion criteria (9 listed)

>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

Key exclusion criteria (10 listed)

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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Tenofovir alafenamideAlso: TAFDaily DOT fixed dose combination of 200 mg emtricitabine (FTC) and 25 mg tenofovir alafenamide (TAF)	Drug	TAF arm
Tenofovir Disoproxil FumarateAlso: TDF or TruvadaDaily DOT fixed dose combination of 200 mg emtricitabine (FTC) and 300 mg tenofovir disoproxil fumarate (TDF)	Drug	TDF arm

Primary outcome

Tenofovir Diphosphate (TFV-DP) Levels in Plasma and Intracellular Levels in Pregnant Women on Daily PrEP
Time frame: 8 week period during Pregnancy
Levels of TFV-DP (geometric mean), comparing the drugs TAF to TDF, observed in pregnancy. Note: Observation of daily PrEP dosing spanned 16 weeks in total, including 8 weeks during pregnancy and 8 weeks in postpartum. Once participants had completed their 8 weeks of in-pregnancy observation, observation of therapy was paused until they entered the postpartum phase.
Tenofovir Diphosphate (TFV-DP) Levels in Plasma and Intracellular Levels in Postpartum Women on Daily PrEP
Time frame: 8 week period during Postpartum (up to 1 year from baseline pregnancy visit)
Levels of TFV-DP (geometric mean), comparing the drugs TAF to TDF, observed in postpartum period. Note: Observation of daily PrEP dosing spanned 16 weeks in total, including 8 weeks during pregnancy and 8 weeks in postpartum. Once participants had completed their 8 weeks of in-pregnancy observation, observation of therapy was paused until they entered the postpartum phase.

1 secondary outcome

Tenofovir Diphosphate (TFV-DP) Concentrations in Plasma and Intracellular Levels Comparing Pregnancy Against Postpartum Women
Time frame: 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).

Results and safety

Results posted to the registry on 3 Sep 2024, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
TAF Arm	20	20
TDF Arm	19	19

Primary outcome: Tenofovir Diphosphate (TFV-DP) Levels in Plasma and Intracellular Levels in Pregnant Women on Daily PrEP

Time frame: 8 week period during Pregnancy. Geometric mean (95% Confidence Interval). Unit: TFV-DP PBMC (fmol/10^6cells)

Measure	TAF Arm n = 18	TDF Arm n = 16
Value	580 (341 to 985)	71 (44 to 112)

Primary outcome: Tenofovir Diphosphate (TFV-DP) Levels in Plasma and Intracellular Levels in Postpartum Women on Daily PrEP

Time frame: 8 week period during Postpartum (up to 1 year from baseline pregnancy visit). Geometric mean (95% Confidence Interval). Unit: TFV-DP PBMC (fmol/10^6 cells)

Measure	TAF Arm n = 18	TDF Arm n = 16
Value	666 (396 to 1123)	73 (50 to 108)

1 secondary outcome is reported in the full results.

Adverse events

Time frame: Participants were then observed for 16 weeks* of daily PrEP dosing *This included 8 weeks of observation during pregnancy and 8 weeks in postpartum. Once participants had completed their 8 weeks of in-pregnancy observation, observation of therapy was paused until they entered the postpartum phase. PrEP dosing was not observed or measured during this pause, but participants were supplied with sufficient pills during this time and were encouraged to continue with daily use.. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
TAF Arm	9 of 20 (45%)	0 of 20 (0%)	0 of 20
TDF Arm	5 of 19 (26.3%)	0 of 19 (0%)	0 of 19

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 3 Sep 2024.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Individual participant dataSharing planned: No

Related trials for Hiv

Not yet recruiting
HealthMpowerment Korea: Pilot Testing the Cultural Adaptation of a Digital HIV Intervention for Men Who Have Sex With Men in South Korea
HIV Infections, HIV Prevention and Care
Not yet recruiting
Prescribe to Prevent HIV: A Hybrid Trial Helping Addiction Clinics Prevent HIV & Infections Through Safer Drug Use Support
People Who Use Opioids/People With Opioid Use Disorder (OUD)
Recruiting
Evaluating the Impact of Using the B-OK Bottles for HIV and ART Literacy in South Africa
HIV, HIV Treatment
Recruiting
Trial Phase: Syndemic Adapted Medly Uganda
Mental Health
RecruitingObservational study
Olfactory Function and Model-Based Behavior in People Living With HIV and SUD
HIV, Substance Use Disorder

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Landon Myer, MD principal investigator

UCT

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Tenofovir alafenamide and Tenofovir Disoproxil Fumarate in people with Hiv, run by University of California, Los Angeles at 1 site in South Africa.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 9 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 3 Sep 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in South Africa. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 3 Sep 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Tenofovir Diphosphate (TFV-DP) Levels in Plasma and Intracellular Levels in Pregnant Women on Daily PrEP (time frame: 8 week period during Pregnancy). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04937881.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Sep 2024.