Pre-Exposure Prophylaxis Dosing in Pregnancy to Optimize HIV Prevention (PREP-P)

Correcting Pre-Exposure Prophylaxis (PrEP) Dosing and Adherence Benchmarks in Pregnancy to Optimize HIV Prevention (PrEP-P): A Randomized Comparative Pharmacokinetic Trial

This trial is a prospective, multi-center, randomized comparison study of 2 Pre-Exposure Prophylaxis (PrEP) pharmacokinetic (PK) dosing regimens from 1st trimester through 12 weeks following delivery (postpartum) to achieve study objectives which include PK, safety monitoring for maternal and fetal/infant safety signals, and adherence.

Study Overview

• Status: Withdrawn
• Conditions: Pregnancy; HIV-1-infection
• Intervention / Treatment: Drug: Standard dose Truvada®; Drug: Pregnancy-adjusted dose Truvada®

Detailed Description

Study participants will be randomized to one of two parallel study arms, involving dosing of tenofovir disoproxil sodium/emtricitabine (TDF/FTC). The investigators will be recruiting and enrolling in the late 1st (preferred) and 2nd trimesters of pregnancy to capture the changes in kidney function and blood flow through the kidneys that appear to start in the late 1st trimester and are most significant in the 2nd and 3rd trimesters of pregnancy. Given the unknown time frame for the return to pre-pregnancy physiologic state and the increased risk of HIV acquisition postpartum, participants will be continued on study dose PrEP until after participants' 1-3 week postpartum visit, after which all participants will be dispensed standard dose PrEP. A 6-12 week postpartum study visit will also be performed to evaluate the timing of return to non-pregnant plasma drug levels during the postpartum period.

PK Sampling. Primary PK data will be derived from up to 7 study visits with PK sampling, including two PK visits in each trimester and postpartum. All PK visits sample blood before an observed PrEP dose. .

Safety Sampling. Maternal safety assessments will continue until 6 months postpartum. Fetal evaluation includes non-invasive limited ultrasound (US) and biophysical profiles (BPP) at study visits and 2nd and 3rd trimester interval growth US, and chart review of all before birth assessments. At birth, the investigators will obtain cord blood plasma to assess for mitochondrial function. Infant safety assessments will continue until 1 year of life. Infants will undergo swaddled Dual-energy X-ray absorptiometry (DXA) scans (without sedation) at 3-6, 24-28, and 50-54 weeks of age. The investigators will assess kidney function by blood sample at 3-6 weeks of life and repeated at 24-28 weeks.

• Study Type: Interventional
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• age 18 years or older
• Able to speak English, French, or Spanish
• Able and willing to provide written informed consent
• Viable first (preferable) or second trimester intrauterine pregnancy
• Creatinine clearance >70 ml/min
• Negative HIV test and no signs/symptoms of acute HIV infection,
• Documented negative hepatitis B virus status.

Exclusion Criteria:

• HIV positive at any time in the study. All neonates of mothers participating in the trial will be recruited, regardless of gestational age at delivery or congenital anomalies/comorbidities.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Standard Dose Truvada®; Standard Dose Truvada® - Tenofovir disoproxil fumarate (TDF) 300 mg/Emtricitabine (FTC) 200 mg fixed dose combination (Truvada®), one tablet each day	Drug: Standard dose Truvada®; TDF/FTC fixed dose combination, 300 mg TDF/200 mg FTC, one tablet each day; Other Names: Tenofovir Disoproxil Fumarate/Emtricitabine; TDF/FTC
Experimental: Pregnancy-Adjusted Truvada®; Pregnancy-Adjusted dose Truvada® - Tenofovir disoproxil fumarate (TDF) 300 mg/Emtricitabine (FTC) 200 mg fixed dose combination (Truvada®), two tablets each day	Drug: Pregnancy-adjusted dose Truvada®; TDF/FTC fixed dose combination, 300 mg TDF/200 mg FTC, two tablets each day; Other Names: Tenofovir Disoproxil Fumarate/Emtricitabine; TDF/FTC

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Plasma Tenofovir (TFV) Concentration	Plasma Tenofovir (TFV) Concentration in nanograms per milliliter (ng/mL)	36 weeks
Plasma Emtricitabine (FTC) Concentration	Plasma Emtricitabine (FTC) Concentration in nanograms per milliliter (ng/mL)	36 weeks
Peripheral Blood Mononuclear Cell (PBMC) TFV-Diphosphate (TFV-DP)Concentration	PBMC TFV-DP concentration in femtomoles/million cells (fmol/10E6 cells)	36 weeks
Peripheral Blood Mononuclear Cell (PBMC) FTC-Triphosphate (FTC-TP)Concentration	PBMC TFV-DP concentration in femtomoles/million cells (fmol/10E6 cells)	36 weeks

Collaborators and Investigators

• Sponsor: Johns Hopkins University

Study record dates

Study Major Dates

• Study Start (Anticipated): April 1, 2022
• Primary Completion (Anticipated): September 1, 2027
• Study Completion (Anticipated): April 1, 2028

Study Registration Dates

• First Submitted: February 6, 2019
• First Submitted That Met QC Criteria: February 6, 2019
• First Posted (Actual): February 8, 2019

Study Record Updates

• Last Update Posted (Actual): April 6, 2022
• Last Update Submitted That Met QC Criteria: March 28, 2022
• Last Verified: March 1, 2021

More Information

Terms related to this study

• Keywords: Healthy Volunteer; HIV Prevention
• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Reverse Transcriptase Inhibitors; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Tenofovir; Emtricitabine; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No