Cabotegravir & Rilpivirine Antiretroviral Therapy in Pregnancy (CREATE)

Phase IV Study of the Pharmacokinetics of Long-Acting Injectable Cabotegravir and Rilpivirine in Pregnant and Postpartum Women With HIV in the United States

Phase IV, multi-site, open-label, non-randomized study of the pharmacokinetics (PK) of long-acting injectable cabotegravir and rilpivirine (CAB LA + RPV LA) during pregnancy and postpartum.

Study Overview

• Status: Not yet recruiting
• Conditions: HIV -1 Infection
• Intervention / Treatment: Drug: Every 4-week long-acting injectable cabotegravir and rilpivirine

Detailed Description

Up to 40 adult-participants with HIV viral suppression will be enrolled, in pairs with their infants, to achieve 30 evaluable adult-participants overall. The study will include women who initiated CAB LA + RPV LA outside the study, prior to study entry, either pre-conception (including on the day of conception) or post-conception.

• Study Type: Observational
• Enrollment (Estimated): 40

Contacts and Locations

• Study Contact: Name: Lisa Levy; Phone Number: 2028848480; Email: LLEVY@FHI360.ORG

Study Locations

• United States
  • California
    • La Jolla, California, United States, 92093
      • Site 4601, University of California, UC San Diego CRS
      • Contact: Stephen Spector, MD; Phone Number: 858-534-7055; Email: saspector@ucsd.edu
    • Los Angeles, California, United States, 90033
      • Site 5048, University of Southern California
      • Contact: Alice Stek, MD; Phone Number: 323-226-3353; Email: stek@usc.edu
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Site 5052, University of Colorado
      • Contact: Lisa Abuogi, MD; Phone Number: 303-358-5061; Email: Lisa.Abuogi@childrenscolorado.org
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Site 5030, Emory University School of Medicine
      • Contact: Martina Badell, MD; Phone Number: 404-778-3401; Email: mbadell@emory.edu
  • Illinois
    • Chicago, Illinois, United States, 60614
      • Site 4001, Lurie Children's Hospital of Chicago CRS
      • Contact: Jennifer Jao, MD, MPH; Phone Number: 312-227-4080; Email: jjao@luriechildrens.org
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Site 5092, Johns Hopkins University
      • Contact: Allison Agwu, MD; Phone Number: 410-614-3917; Email: ageorg10@jhmi.edu
  • New York
    • The Bronx, New York, United States, 10461
      • Site 5013, Jacobi Medical Center Bronx
      • Contact: Andrew Wiznia, MD; Phone Number: 718-918-4664; Email: andrew.wiznia@einsteinmed.edu
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Site 6201, University of Pennsylvania
      • Contact: William Short, MD; Phone Number: 267-971-3275; Email: william.short@pennmedicine.upenn.edu
  • Tennessee
    • Memphis, Tennessee, United States, 38105
      • Site 6501, St Jude Children's Research Hospital
      • Contact: Katherine Knapp, MD; Phone Number: 901-595-4645; Email: katherine.knapp@stjude.org
  • Texas
    • Houston, Texas, United States, 77030
      • Site 5128, Baylor College of Medicine/Texas Children's Hospital
      • Contact: Mary Paul, MD; Phone Number: 832-822-1038; Email: mpaul@bcm.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Pregnant women with HIV viral suppression in the United States, age 18 years and older, who initiated CAB LA + RPV LA pre- or post-conception, with an estimated gestational age from 10 0/7 weeks through 23 6/7 weeks at time of entry, and their infants.

Description

Inclusion Criteria:

• Willing and able to provide written informed consent for study participation for self and infant
• At screening, age 18 years or older
• Has a viable, intrauterine, singleton pregnancy with fetal ultrasound with an estimated gestational age (EGA) between 10 0/7 and 23 6/7 weeks (inclusive) at entry
• At entry, intending to deliver at a study-associated medical facility and remain in the geographic area of the study for the duration of anticipated follow-up
• Was diagnosed with HIV prior to the current pregnancy
• Has a documented plasma HIV RNA result less than 50 copies/mL from a specimen collected within 28 days prior to entry
• Has the following laboratory test results from a specimen collected within 28 days prior to entry (1) Grade 2 or lower platelets (greater than or equal to 50,000 cells/mm3 or greater than or equal to 50.00 x 109 cells/L); (2) Grade 1 or lower ALT (less than 2.5 x upper limit of normal; (3) Grade 1 or lower aspartate aminotransferase (AST)
• Received first dose of CAB LA + RPV LA prior to entry (before or after conception of the current pregnancy) and is expected to receive CAB LA + RPV LA on a Q4W schedule for the duration of study participation

Exclusion Criteria:

• History of treatment/virologic failure associated with documented or suspected viral resistance to CAB or RPV (including oral RPV)
• Has any of the following (1) HIV Subtype A6; (2) History of hypersensitivity reaction (HSR), known or suspected allergy to drugs under study, or any other contraindication to CAB or RPV; (3) Current contraindication to IM injection such as a current inflammatory skin condition that compromises the safety of IM injections or a dermatological condition which may interfere with the interpretation of ISRs; (4) Current use or anticipated need of therapeutic anticoagulation; (5) History of known or suspected bleeding disorder; (6) Current severe hepatic impairment (Class C) as determined by Child-Pugh classification; (7) History of suicidal ideation or attempt within six months of entry; (8) History of unstable or poorly controlled seizure disorder; (9) Current tuberculosis infection; (10) Current cervical intraepithelial neoplasia (CIN) 2 or 3, or malignancy other than Kaposi's sarcoma, basal cell carcinoma, or resected, non-invasive cutaneous squamous cell carcinoma
• Has any of the following during the current pregnancy: (1) Abnormal placentation, including placenta previa (complete) and placenta accreta/increta/percreta; (2) Cervical cerclage/cervical incompetence; (3) Abnormal fetal anatomy
• Had any of the following in a previous pregnancy: (1) Eclampsia/Hemolysis, Elevated Liver enzymes and Low Platelets (HELLP) syndrome; (2) Intrauterine fetal demise (EGA greater than 20 weeks) without known nonrecurrent etiology; (3) Spontaneous very preterm delivery (less than 32 weeks); (4) Very LBW (less than 1500 g); (5) Cervical or abdominal cerclage due to cervical incompetence
• Receipt of any prohibited medication within seven days prior to entry
• Enrolled in another clinical trial of an investigational agent, device, or vaccine that may impact the PK of CAB or RPV
• Receipt of an investigational agent or chemotherapy within 30 days prior to study entry
• Adult-participant or fetus has any condition, such as uncontrolled diabetes, hypertension, or other comorbidities, that, in the opinion of the site investigator, would make participation in the study unsafe, complicate interpretation of study outcome data, or otherwise interfere with achieving the study objectives

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Population PK: geometric mean clearance of CAB and RPV in second trimester, third trimester, and postpartum derived from a population PK model	Population PK: geometric mean clearance of CAB and RPV in second trimester, third trimester, and postpartum derived from a population PK model	Measured from study entry through six weeks postpartum
Geometric mean pharmacokinetic trough of CAB and RPV from every 4 week (Q4W) CAB LA and RPV LA measured every 4 weeks in plasma in second trimester, third trimester, and postpartum	Geometric mean pharmacokinetic trough of CAB and RPV from every 4 week (Q4W) CAB LA and RPV LA measured every 4 weeks in plasma in second trimester, third trimester, and postpartum	Measured from study entry through six weeks postpartum

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of adult participants with HIV RNA less than 50 copies/mL at delivery	Percentage of adult participants with HIV RNA less than 50 copies/mL at delivery	Delivery
Percentage of adult participants with virologic escape	Percentage of adult participants with virologic escape, defined as a single measurement of HIV RNA greater than or equal to 200 copies/mL	Measured from study entry through six weeks postpartum
Percentage of adult participants with confirmed virologic failure	Percentage of adult participants with confirmed virologic failure, defined as two successive HIV RNA test results greater than or equal to 200 copies/mL from separate specimens collected at least two weeks apart	Through 6 weeks postpartum
Number of adult participants with HIV resistance to CAB or RPV who had confirmed virologic failure	Number of adult participants with HIV resistance to CAB or RPV using IAS-USA, in participants who experienced confirmed virologic failure	Through 6 weeks postpartum
Number of infant participants with perinatal transmission	Number of infant participants with perinatal transmission	Birth and six weeks post-birth
Percentage of adult participants with at least one Grade 3 or higher adverse event	Percentage of adult participants with at least one Grade 3 or higher adverse event	Measured from study entry through six weeks postpartum
Percentage of adult participants with at least one serious adverse event	Percentage of adult participants with at least one serious adverse event	Measured from study entry through six weeks postpartum
Percentage of infant participants with at least one serious adverse event	Percentage of infant participants with at least one serious adverse event	Measured from birth through six weeks post-birth
Percentage of adult participants with spontaneous abortion	Percentage of adult participants with spontaneous abortion less than 20 weeks gestation	Through 6 weeks postpartum
Percentage of adult participants with fetal demise/stillbirth	Percentage of adult participants with fetal demise/stillbirth, at greater than or equal to 20 weeks gestation	Through 6 weeks postpartum
Percentage of infant participants born small for gestational age	Percentage of infant participants born small for gestational age, where birthweight is less than 10th percentile for sex and gestational age assigned at birth, based on Intergrowth 21st Standards	Birth
Percentage of infant participants with low birth weight	Percentage of infant participants with low birth weight, defined as less than 2500 grams	Birth
Percentage of infant participants born preterm	Percentage of infant participants born preterm, defined as less than 37 weeks gestation	Birth
Percentage of mother-infant pairs with occurrence of any adverse pregnancy outcome	Percentage of mother-infant pairs with occurrence of any adverse pregnancy outcome. Outcomes include: spontaneous abortion (<20 weeks gestation), stillbirth (≥20 weeks gestation), preterm delivery (<37 gestational weeks), small for gestational age (<10th percentile per INTERGROWTH 21st Standards), or neonatal death	Through 6 weeks postpartum
Percentage of infant participants with a congenital anomaly	Percentage of infant participants with a congenital anomaly based on the Metropolitan Atlanta Congenital Defects Program (MACDP) definition of defect	Birth
Percentage of infant deaths	Percentage of infant deaths	Measured from birth through six weeks post-birth
Percentage of adult participants who would recommend CAB LA and RPV LA injections for other people living with HIV during pregnancy	Percentage of adult participants who would recommend CAB LA and RPV LA injections	Six weeks postpartum

Collaborators and Investigators

• Sponsor: International Maternal Pediatric Adolescent AIDS Clinical Trials Group
• Collaborators: National Institute of Allergy and Infectious Diseases (NIAID); Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD); National Institute of Mental Health (NIMH)
• Investigators: Study Chair: Rachel Scott, MD, MPH, MedStar Washington Hospital Center & MedStar Health Research Institute

Study record dates

Study Major Dates

• Study Start (Estimated): July 15, 2026
• Primary Completion (Estimated): February 15, 2028
• Study Completion (Estimated): February 15, 2028

Study Registration Dates

• First Submitted: May 27, 2026
• First Submitted That Met QC Criteria: June 9, 2026
• First Posted (Actual): June 10, 2026

Study Record Updates

• Last Update Posted (Actual): June 10, 2026
• Last Update Submitted That Met QC Criteria: June 9, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: HIV; Pregnancy; CAB LA + RPV LA
• Additional Relevant MeSH Terms: Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrimidines; Nitriles; Rilpivirine
• Other Study ID Numbers: IMPAACT 2050; UM1AI068632 (U.S. NIH Grant/Contract); UM1AI068616 (U.S. NIH Grant/Contract); UM1AI106716 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Individual participant data that underlie results in the publication, after deidentification.
• IPD Sharing Time Frame: Beginning 3 months following publication and available throughout period of funding of the International Maternal Pediatric Adolescent AIDS Clinical Trial (IMPAACT) Network by NIH.
• IPD Sharing Access Criteria: With whom? Researchers who provide a methodologically sound proposal for use of the data that is approved by the IMPAACT Network.; For what types of analyses? To achieve aims in the proposal approved by the IMPAACT Network.; By what mechanism will data be made available? Researchers may submit a request for access to data using the IMPAACT "Data Request" form at: https://www.impaactnetwork.org/studies/submit-research-proposal. Researchers of approved proposals will need to sign an IMPAACT Data Use Agreement before receiving the data.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No