Trial Outcomes & Findings for PK of TAF and TDF for PrEP in Pregnant and Postpartum Women (NCT NCT04937881)

Last Updated: 2024-09-03

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

39 participants

Primary outcome timeframe

8 week period during Pregnancy

Results posted on

2024-09-03

Participant Flow

Between June 2022 and October 2022, the study enrolled participants from a large, urban clinic outside of Cape Town, South Africa. Inclusion criteria required the women to: (1) be aged 18 and older; (2) test HIV-negative; (3) be between 20-30 weeks of gestation; (4) own a smart phone; and (5) to consent to daily video observations of taking a PrEP pill.

We received IRB approval to increase the sample size to up to 30 participants per group to account for potential attrition and pregnancy loss (total up to N=60 women).

Participant milestones

Participant milestones
Measure	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 Tenofovir alafenamide: Daily DOT fixed dose combination of 200 mg emtricitabine (FTC) and 300 mg tenofovir disoproxil fumarate (TDF)	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 Tenofovir Disoproxil Fumarate: Daily DOT fixed dose combination of 200 mg emtricitabine (FTC) and 25 mg tenofovir alafenamide (TAF)
Overall Study STARTED	20	19
Overall Study COMPLETED	20	19
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	TAF Arm n=20 Participants 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 Tenofovir alafenamide: Daily DOT fixed dose combination of 200 mg emtricitabine (FTC) and 300 mg tenofovir disoproxil fumarate (TDF)	TDF Arm n=19 Participants 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 Tenofovir Disoproxil Fumarate: Daily DOT fixed dose combination of 200 mg emtricitabine (FTC) and 25 mg tenofovir alafenamide (TAF)	Total n=39 Participants Total of all reporting groups
Age, Continuous	28 years n=5 Participants	29 years n=7 Participants	28 years n=5 Participants
Age, Customized Age, Categorical · 18-25 years	6 Participants n=5 Participants	6 Participants n=7 Participants	12 Participants n=5 Participants
Age, Customized Age, Categorical · >25 years	14 Participants n=5 Participants	13 Participants n=7 Participants	27 Participants n=5 Participants
Sex: Female, Male Female	20 Participants n=5 Participants	19 Participants n=7 Participants	39 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	20 Participants n=5 Participants	19 Participants n=7 Participants	39 Participants n=5 Participants
Race (NIH/OMB) White	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment South Africa	20 Participants n=5 Participants	19 Participants n=7 Participants	39 Participants n=5 Participants

PRIMARY outcome

Timeframe: 8 week period during Pregnancy

Outcome measures

Outcome measures
Measure	TAF Arm n=18 Participants 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 Tenofovir alafenamide: Daily DOT fixed dose combination of 200 mg emtricitabine (FTC) and 25 mg tenofovir alafenamide (TAF)	TDF Arm n=16 Participants 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 Tenofovir Disoproxil Fumarate: Daily DOT fixed dose combination of 200 mg emtricitabine (FTC) and 300 mg tenofovir disoproxil fumarate (TDF)
Tenofovir Diphosphate (TFV-DP) Levels in Plasma and Intracellular Levels in Pregnant Women on Daily PrEP	580 TFV-DP PBMC (fmol/10^6cells) Interval 341.0 to 985.0	71 TFV-DP PBMC (fmol/10^6cells) Interval 44.0 to 112.0

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	TAF Arm n=18 Participants 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 Tenofovir alafenamide: Daily DOT fixed dose combination of 200 mg emtricitabine (FTC) and 25 mg tenofovir alafenamide (TAF)	TDF Arm n=16 Participants 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 Tenofovir Disoproxil Fumarate: Daily DOT fixed dose combination of 200 mg emtricitabine (FTC) and 300 mg tenofovir disoproxil fumarate (TDF)
Tenofovir Diphosphate (TFV-DP) Levels in Plasma and Intracellular Levels in Postpartum Women on Daily PrEP	666 TFV-DP PBMC (fmol/10^6 cells) Interval 396.0 to 1123.0	73 TFV-DP PBMC (fmol/10^6 cells) Interval 50.0 to 108.0

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	TAF Arm n=20 Participants 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 Tenofovir alafenamide: Daily DOT fixed dose combination of 200 mg emtricitabine (FTC) and 25 mg tenofovir alafenamide (TAF)	TDF Arm n=19 Participants 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 Tenofovir Disoproxil Fumarate: Daily DOT fixed dose combination of 200 mg emtricitabine (FTC) and 300 mg tenofovir disoproxil fumarate (TDF)
Tenofovir Diphosphate (TFV-DP) Concentrations in Plasma and Intracellular Levels Comparing Pregnancy Against Postpartum Women TFV-DP steady-state concentration in Pregnancy (at 8-weeks follow up via DBS)	611.3 TDF:fmol/3mm punch; TAF:fmol/3mm punch Interval 396.6 to 754.5	410.0 TDF:fmol/3mm punch; TAF:fmol/3mm punch Interval 271.0 to 571.1
Tenofovir Diphosphate (TFV-DP) Concentrations in Plasma and Intracellular Levels Comparing Pregnancy Against Postpartum Women TFV-DP steady-state concentration in Postpartum (at 8-weeks follow up via DBS)	940.5 TDF:fmol/3mm punch; TAF:fmol/3mm punch Interval 630.2 to 1259.3	518.3 TDF:fmol/3mm punch; TAF:fmol/3mm punch Interval 285.7 to 780.1

Adverse Events

TAF Arm

Serious events: 9 serious events

Other events: 0 other events

Deaths: 0 deaths

TDF Arm

Serious events: 5 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	TAF Arm n=20 participants at risk 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 Tenofovir alafenamide: Daily DOT fixed dose combination of 200 mg emtricitabine (FTC) and 300 mg tenofovir disoproxil fumarate (TDF)	TDF Arm n=19 participants at risk 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 Tenofovir Disoproxil Fumarate: Daily DOT fixed dose combination of 200 mg emtricitabine (FTC) and 25 mg tenofovir alafenamide (TAF)
Pregnancy, puerperium and perinatal conditions C-Section Delivery (Emergency)	20.0% 4/20 • Number of events 4 • 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. Serious Adverse Events, defined as any untoward occurrence that 1) results in death, 2) is life threatening, 3) requires patient hospitalization, 4) results in a congenital anomaly/ birth defect, 5) results in persistent or significant disability/incapacity, or 6) is a medically significant event or reaction, were recorded among all participants during periods of observation, according to South African Health Products Regulatory Authority (SAHPRA) safety reporting guidelines.	5.3% 1/19 • Number of events 1 • 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. Serious Adverse Events, defined as any untoward occurrence that 1) results in death, 2) is life threatening, 3) requires patient hospitalization, 4) results in a congenital anomaly/ birth defect, 5) results in persistent or significant disability/incapacity, or 6) is a medically significant event or reaction, were recorded among all participants during periods of observation, according to South African Health Products Regulatory Authority (SAHPRA) safety reporting guidelines.
Psychiatric disorders Attempted suicide	5.0% 1/20 • Number of events 1 • 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. Serious Adverse Events, defined as any untoward occurrence that 1) results in death, 2) is life threatening, 3) requires patient hospitalization, 4) results in a congenital anomaly/ birth defect, 5) results in persistent or significant disability/incapacity, or 6) is a medically significant event or reaction, were recorded among all participants during periods of observation, according to South African Health Products Regulatory Authority (SAHPRA) safety reporting guidelines.	0.00% 0/19 • 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. Serious Adverse Events, defined as any untoward occurrence that 1) results in death, 2) is life threatening, 3) requires patient hospitalization, 4) results in a congenital anomaly/ birth defect, 5) results in persistent or significant disability/incapacity, or 6) is a medically significant event or reaction, were recorded among all participants during periods of observation, according to South African Health Products Regulatory Authority (SAHPRA) safety reporting guidelines.
Social circumstances Intimate Partner Violence	5.0% 1/20 • Number of events 1 • 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. Serious Adverse Events, defined as any untoward occurrence that 1) results in death, 2) is life threatening, 3) requires patient hospitalization, 4) results in a congenital anomaly/ birth defect, 5) results in persistent or significant disability/incapacity, or 6) is a medically significant event or reaction, were recorded among all participants during periods of observation, according to South African Health Products Regulatory Authority (SAHPRA) safety reporting guidelines.	5.3% 1/19 • Number of events 1 • 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. Serious Adverse Events, defined as any untoward occurrence that 1) results in death, 2) is life threatening, 3) requires patient hospitalization, 4) results in a congenital anomaly/ birth defect, 5) results in persistent or significant disability/incapacity, or 6) is a medically significant event or reaction, were recorded among all participants during periods of observation, according to South African Health Products Regulatory Authority (SAHPRA) safety reporting guidelines.
Pregnancy, puerperium and perinatal conditions Premature Birth	10.0% 2/20 • Number of events 2 • 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. Serious Adverse Events, defined as any untoward occurrence that 1) results in death, 2) is life threatening, 3) requires patient hospitalization, 4) results in a congenital anomaly/ birth defect, 5) results in persistent or significant disability/incapacity, or 6) is a medically significant event or reaction, were recorded among all participants during periods of observation, according to South African Health Products Regulatory Authority (SAHPRA) safety reporting guidelines.	0.00% 0/19 • 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. Serious Adverse Events, defined as any untoward occurrence that 1) results in death, 2) is life threatening, 3) requires patient hospitalization, 4) results in a congenital anomaly/ birth defect, 5) results in persistent or significant disability/incapacity, or 6) is a medically significant event or reaction, were recorded among all participants during periods of observation, according to South African Health Products Regulatory Authority (SAHPRA) safety reporting guidelines.
Infections and infestations Shigella dysenteriae, Infant	5.0% 1/20 • Number of events 1 • 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. Serious Adverse Events, defined as any untoward occurrence that 1) results in death, 2) is life threatening, 3) requires patient hospitalization, 4) results in a congenital anomaly/ birth defect, 5) results in persistent or significant disability/incapacity, or 6) is a medically significant event or reaction, were recorded among all participants during periods of observation, according to South African Health Products Regulatory Authority (SAHPRA) safety reporting guidelines.	0.00% 0/19 • 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. Serious Adverse Events, defined as any untoward occurrence that 1) results in death, 2) is life threatening, 3) requires patient hospitalization, 4) results in a congenital anomaly/ birth defect, 5) results in persistent or significant disability/incapacity, or 6) is a medically significant event or reaction, were recorded among all participants during periods of observation, according to South African Health Products Regulatory Authority (SAHPRA) safety reporting guidelines.
Reproductive system and breast disorders Bartholin cyst	0.00% 0/20 • 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. Serious Adverse Events, defined as any untoward occurrence that 1) results in death, 2) is life threatening, 3) requires patient hospitalization, 4) results in a congenital anomaly/ birth defect, 5) results in persistent or significant disability/incapacity, or 6) is a medically significant event or reaction, were recorded among all participants during periods of observation, according to South African Health Products Regulatory Authority (SAHPRA) safety reporting guidelines.	5.3% 1/19 • Number of events 1 • 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. Serious Adverse Events, defined as any untoward occurrence that 1) results in death, 2) is life threatening, 3) requires patient hospitalization, 4) results in a congenital anomaly/ birth defect, 5) results in persistent or significant disability/incapacity, or 6) is a medically significant event or reaction, were recorded among all participants during periods of observation, according to South African Health Products Regulatory Authority (SAHPRA) safety reporting guidelines.
Pregnancy, puerperium and perinatal conditions Premature rupture of membranes	0.00% 0/20 • 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. Serious Adverse Events, defined as any untoward occurrence that 1) results in death, 2) is life threatening, 3) requires patient hospitalization, 4) results in a congenital anomaly/ birth defect, 5) results in persistent or significant disability/incapacity, or 6) is a medically significant event or reaction, were recorded among all participants during periods of observation, according to South African Health Products Regulatory Authority (SAHPRA) safety reporting guidelines.	5.3% 1/19 • Number of events 1 • 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. Serious Adverse Events, defined as any untoward occurrence that 1) results in death, 2) is life threatening, 3) requires patient hospitalization, 4) results in a congenital anomaly/ birth defect, 5) results in persistent or significant disability/incapacity, or 6) is a medically significant event or reaction, were recorded among all participants during periods of observation, according to South African Health Products Regulatory Authority (SAHPRA) safety reporting guidelines.
Pregnancy, puerperium and perinatal conditions Fetal tachycardia	0.00% 0/20 • 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. Serious Adverse Events, defined as any untoward occurrence that 1) results in death, 2) is life threatening, 3) requires patient hospitalization, 4) results in a congenital anomaly/ birth defect, 5) results in persistent or significant disability/incapacity, or 6) is a medically significant event or reaction, were recorded among all participants during periods of observation, according to South African Health Products Regulatory Authority (SAHPRA) safety reporting guidelines.	5.3% 1/19 • Number of events 1 • 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. Serious Adverse Events, defined as any untoward occurrence that 1) results in death, 2) is life threatening, 3) requires patient hospitalization, 4) results in a congenital anomaly/ birth defect, 5) results in persistent or significant disability/incapacity, or 6) is a medically significant event or reaction, were recorded among all participants during periods of observation, according to South African Health Products Regulatory Authority (SAHPRA) safety reporting guidelines.

Other adverse events

Adverse event data not reported

Additional Information

Dvora Joseph Davey

UCLA

Phone: 3107011526

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place