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

NCT ID: NCT03834909

Last Updated: 2022-04-06

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE1
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-04-30
• Study Completion Date: 2028-04-30

Brief Summary

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

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.

Conditions

Pregnancy; HIV-1-infection

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

Standard Dose Truvada®

Standard Dose Truvada® - Tenofovir disoproxil fumarate (TDF) 300 mg/Emtricitabine (FTC) 200 mg fixed dose combination (Truvada®), one tablet each day

Group Type: ACTIVE_COMPARATOR

Standard dose Truvada®

Intervention Type: DRUG

TDF/FTC fixed dose combination, 300 mg TDF/200 mg FTC, one tablet each day

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

Group Type: EXPERIMENTAL

Pregnancy-adjusted dose Truvada®

Intervention Type: DRUG

TDF/FTC fixed dose combination, 300 mg TDF/200 mg FTC, two tablets each day

Interventions

Standard dose Truvada®

TDF/FTC fixed dose combination, 300 mg TDF/200 mg FTC, one tablet each day

Intervention Type: DRUG

Pregnancy-adjusted dose Truvada®

TDF/FTC fixed dose combination, 300 mg TDF/200 mg FTC, two tablets each day

Intervention Type: DRUG

Other Intervention Names

Tenofovir Disoproxil Fumarate/Emtricitabine; TDF/FTC; Tenofovir Disoproxil Fumarate/Emtricitabine; TDF/FTC

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: Yes

Sponsors

Johns Hopkins University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Craig Hendrix, MD

Role: PRINCIPAL_INVESTIGATOR

Johns Hopkins University