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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Pregnancy, HIV-1-infection

Intervention / Treatment
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* Drug: Standard dose Truvada®
* Drug: Pregnancy-adjusted dose Truvada®


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: The investigators will randomly allocate participants in a 1:1 ratio to two parallel study arms (based on a computer generated randomization scheme).
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Standard Dose Truvada®<br>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®<br>* TDF/FTC fixed dose combination, 300 mg TDF/200 mg FTC, one tablet each day<br>* Other names: TDF/FTC;|
| Experimental: Pregnancy-Adjusted Truvada®<br>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®<br>* TDF/FTC fixed dose combination, 300 mg TDF/200 mg FTC, two tablets each day<br>* Other names: TDF/FTC;|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HIV Prevention, Healthy Volunteer