NCT04937881: PrEP-PP PK

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

Completed Phase 3 Results posted Last updated 3 September 2024

What this trial tests

Phase 3 trial testing Tenofovir alafenamide in Hiv in 39 participants. Completed in 1 September 2023.

Timeline

13 June 2022

Primary endpoint
17 April 2023

1 September 2023

Quick facts

Lead sponsor	University of California, Los Angeles
Phase	Phase 3
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	none
Primary purpose	prevention
Enrollment	39
Start date	13 June 2022
Primary completion	17 April 2023
Estimated completion	1 September 2023
Sites	1 location across South Africa

Drugs / interventions tested

• Tenofovir alafenamide (TENOFOVIR ALAFENAMIDE) — full drug profile →
• Tenofovir Disoproxil Fumarate — full drug profile →

Conditions studied

• Hiv — all drugs for Hiv →

Sponsor

University of California, Los Angeles

Who can join

18 and older, female only, with Hiv. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

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

Group	Value	95% CI
TAF Arm	580	341 – 985
TDF Arm	71	44 – 112

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

Group	Value	95% CI
TAF Arm	666	396 – 1123
TDF Arm	73	50 – 108

Tenofovir Diphosphate (TFV-DP) Concentrations in Plasma and Intracellular Levels Comparing Pregnancy Against Postpartum Women Secondary · 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).

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.

TFV-DP steady-state concentration in Pregnancy (at 8-weeks follow up via DBS)

Group	Value	95% CI
TAF Arm	611.3	396.6 – 754.5
TDF Arm	410.0	271.0 – 571.1

TFV-DP steady-state concentration in Postpartum (at 8-weeks follow up via DBS)

Group	Value	95% CI
TAF Arm	940.5	630.2 – 1259.3
TDF Arm	518.3	285.7 – 780.1

Adverse events — posted to ClinicalTrials.gov

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.. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

TAF Arm

Serious: 9/20 (45%)

Deaths: 0/20

TDF Arm

Serious: 5/19 (26%)

Deaths: 0/19

Serious adverse events (8 terms)

Reaction	System	TAF Arm	TDF Arm
C-Section Delivery (Emergency)	Pregnancy, puerperium and perinatal conditions	—	—
Premature Birth	Pregnancy, puerperium and perinatal conditions	—	—
Attempted suicide	Psychiatric disorders	—	—
Intimate Partner Violence	Social circumstances	—	—
Shigella dysenteriae, Infant	Infections and infestations	—	—
Bartholin cyst	Reproductive system and breast disorders	—	—
Premature rupture of membranes	Pregnancy, puerperium and perinatal conditions	—	—
Fetal tachycardia	Pregnancy, puerperium and perinatal conditions	—	—

Most-reported serious reactions: C-Section Delivery (Emergency), Premature Birth, Attempted suicide, Intimate Partner Violence, Shigella dysenteriae, Infant, Bartholin cyst, Premature rupture of membranes, Fetal tachycardia.

Data from ClinicalTrials.gov NCT04937881 adverse events section.

Sponsor's own 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.

Publications & conference data

1 peer-reviewed publication reference this trial (live from Europe PMC):

1. Where are the pregnant and breastfeeding women in new pre-exposure prophylaxis trials? The imperative to overcome the evidence gap.
   Joseph Davey DL, Bekker LG, Bukusi EA, Chi BH, et al · · 2022 · cited 35× · PMID 35090604 · DOI 10.1016/s2352-3018(21)00280-0