Phase 2
Completed N=80
Evaluating the Pharmacokinetics, Feasibility, Acceptability, and Safety of Oral Pre-Exposure Prophylaxis for HIV Prevention During Pregnancy and Postpartum
Source: ClinicalTrials.gov NCT03386578 ↗Enrolled (actual)
80
Serious AEs
9.2%
Results posted
Feb 2025
Primary outcomePrimary: Estimated Threshold of Maternal Steady-state Tenofovir Diphosphate (TFV-DP) Concentration Levels Corresponding to Optimal Adherence in the PK Component — 965; 1050 fmol/punch
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.
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 |
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
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. Informational only — not medical advice.