Phase 2 N=80 Prevention

Evaluating the Pharmacokinetics, Feasibility, Acceptability, and Safety of Oral Pre-Exposure Prophylaxis for HIV Prevention During Pregnancy and Postpartum

HIV Infections

Bottom Line

View on ClinicalTrials.gov: NCT03386578 ↗

Enrolled (actual)

Serious AEs

9.2%

Results posted

Feb 2025

Primary outcome: Primary: Estimated Threshold of Maternal Steady-state Tenofovir Diphosphate (TFV-DP) Concentration Levels Corresponding to Optimal Adherence in the PK Component — 965; 1050 fmol/punch

Study Design & Population

Study type: Interventional
Phase: Phase 2
Interventions: Emtricitabine/Tenofovir Disoproxil Fumarate (FTC/TDF) (Drug); Behavioral HIV risk reduction package (Behavioral); Enhanced adherence support (Behavioral)
Age: Pediatric, Adult · 16+ yrs
Sex: Female
Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Primary completion: Oct 2023

Outcome Measures

Outcome	Result	p-value
PRIMARY Estimated Threshold of Maternal Steady-state Tenofovir Diphosphate (TFV-DP) Concentration Levels Corresponding to Optimal Adherence in the PK Component	965; 1050	—
PRIMARY Proportion of Mothers With Optimal Adherence at Antepartum Study Week 4	0.15	—
PRIMARY Proportion of Mothers With Optimal Adherence at Antepartum Study Week 8	0.23	—
PRIMARY Proportion of Mothers With Optimal Adherence at Antepartum Study Week 12	0.27	—
PRIMARY Proportion of Mothers With Optimal Adherence at Delivery	0.31	—
PRIMARY Proportion of Mothers With Optimal Adherence at Postpartum Week 6	0.20	—
PRIMARY Proportion of Mothers With Optimal Adherence at Postpartum Week 14	0.17	—
PRIMARY Proportion of Mothers With Optimal Adherence at Postpartum Week 26	0.15	—
PRIMARY Proportion of Maternal Visits With Optimal Adherence During Study Follow-up	0.21	—
PRIMARY Incidence Rate of Maternal Adverse Events Per 100 Person-years	29.4; 18.2	—
PRIMARY Number of Composite Adverse Pregnancy Outcomes	51; 28	0.68
PRIMARY Incidence Rate of Infant Grade 3 or Higher Adverse Events Per 100 Person-years	42.6; 33.1	—
PRIMARY Mean Infant Bone Mineral Content of Whole Body at Birth	68.2; 65.8	0.18
PRIMARY Mean Infant Bone Mineral Content of Lumbar Spine at Birth	1.9; 1.8	0.39
PRIMARY Mean Infant Bone Mineral Content of Lumbar Spine at Week 26	3.2; 3.1	0.12
PRIMARY Mean Infant Creatinine Levels at Birth in the PrEP Comparison Component	0.4; 0.3	0.70
PRIMARY Mean Infant Creatinine Levels at Week 26 in the PrEP Comparison Component	0.2; 0.2	0.58
PRIMARY Mean Infant Creatinine Clearance (CrCl) Rate at Birth in the PrEP Comparison Component	84.4; 74.6	0.08
PRIMARY Mean Infant Creatinine Clearance (CrCl) Rate at Week 26 in the PrEP Comparison Component	143.3; 140.1	0.52
PRIMARY Mean Infant Length-for-age Z-score at Birth	-0.4; -0.6	0.30
PRIMARY Mean Infant Length-for-age Z-score at Week 26	-0.6; -0.8	0.06
SECONDARY Maternal Median Steady State TFV-DP Concentration Levels at Study Week 12 During Pregnancy and Postpartum	965; 1406	<0.01 sig

Summary

The purpose of this study was to evaluate the pharmacokinetics, feasibility, acceptability, and safety of a fixed-dose combination of emtricitabine and tenofovir disoproxil fumarate (FTC/TDF) as oral daily pre-exposure prophylaxis (PrEP) to prevent HIV during pregnancy and postpartum in adolescents and young women and their infants.

Eligibility Criteria

PK Component (Groups 1 and 2) Inclusion Criteria:

At study entry, pregnant or recently delivered, in one of the following two enrollment windows:
Group 1: Gestational age of 14 to 24 weeks.
Group 2: 6 to 12 weeks postpartum.
Willing to initiate daily PrEP for 12 weeks under directly observed therapy.
HIV and Hepatitis B negative.
At screening:
Grade 1 or normal alanine transaminase (ALT), hemoglobin (HB), absolute neutrophil count (ANC) and normal creatinine clearance (CrCl).
Negative or trace proteinuria (less than Grade 1).
Normal dipstick urine for glucose (less than Grade 1).
Mother weighs greater than 35 kg.
Intention to stay within the study site's catchment area for at least 12 weeks (or through delivery).

Exclusion Criteria (PK Component and PrEP Comparison Component):

Any current significant uncontrolled, active or chronic disease process.
History of any of the following:
Sickle cell anemia, chronic bleeding, blood transfusion within the past 120 days or other blood dyscrasias
Bone fracture not explained by trauma
Allergy/sensitivity to FTC/TDF or its components
Fetus has a known or suspected major congenital anomaly
Mother has confirmed renal insufficiency, a history of renal parenchymal disease or single kidney
Current use of prohibited medications listed in the protocol
Concurrent participation in any biomedical HIV prevention or investigational drug in an HIV vaccine or microbicide study
Past participation in an HIV vaccine study
Currently taking a PrEP regimen from non-study sources
Any other condition or adverse social situation
Past participation in IMPAACT 2009

PrEP Comparison Component (Cohorts 1 and 2) Inclusion Criteria:

At screening, evidence of a viable singleton pregnancy with gestational age of 32 weeks or less.
Within 14 days prior to study entry, negative HIV RNA test.
HIV and Hepatitis B negative.
At screening:
Grade 1 or normal ALT, HB, ANC and normal CrCl.
Negative or trace proteinuria (less than Grade 1).
Normal dipstick urine for glucose (less than Grade 1).
Intention to stay within the study site's catchment area through 26 weeks postpartum
A cellular phone that is able to receive SMS messages, and for Cohort 1 only, is also able to send SMS messages.
Cohort 1 only: Willingness to take PrEP from pregnancy up to 26 weeks postpartum
Cohort 2 only: Unwillingness to take PrEP from pregnancy up to 26 weeks postpartum
Mother weighs greater than 35 kg
Mother is literate in one or more of the study languages

View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT03386578). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.