EMBRACE (Evaluation of Maternal and Baby Outcome Registry After Chemoprophylactic Exposure) (EMBRACE)

HIV Prevention Agent Pregnancy Exposure Registry: EMBRACE Study

The Prevention Agent Pregnancy Exposure Registry, also known as EMBRACE (Evaluation of Maternal and Baby Outcome Registry After Chemoprophylactic Exposure) is a prospective observational cohort investigation of exposures to study agents under investigation for HIV prevention. The study population will consist of female participants who are identified as becoming pregnant during their participation in a microbicide or PrEP trial, or who have had planned exposures in pregnancy safety studies as well as their babies resulting from these pregnancies. This study will only enroll babies who have not yet reached their 1 year birth date.

Study Overview

• Status: Completed
• Conditions: Pregnancy Related

Detailed Description

The Prevention Agent Pregnancy Exposure Registry, also known as EMBRACE (Evaluation of Maternal and Baby Outcome Registry After Chemoprophylactic Exposure) is a prospective observational cohort study of maternal exposures to investigational HIV prevention agents. Approximately 550 pregnant participants and 400 live infants will be offered enrollment. The study population will consist of current or recent female participants identified as becoming pregnant during microbicide or PrEP trials, or who have had planned exposures in pregnancy safety studies. This study will also include infants resulting from those pregnancies. This protocol will monitor for adverse pregnancy and delivery outcomes, monitor the prevalence of major malformations, evaluate growth parameters of infants during the first year of life, and evaluate the prevalence and persistence of HIV drug resistance mutations in a cohort of infants who were either exposed to active study agents or not exposed to active study agents while in utero.

• Study Type: Observational
• Enrollment (Actual): 873

Contacts and Locations

Study Locations

• South Africa
  • Durban, South Africa
    • South African MRC HIV CTU Med Research Council; Botha's Hill Clinical Research Site
  • Durban, South Africa
    • South African MRC HIV CTU Med Research Council; Isipingo
  • Durban, South Africa
    • South African MRC HIV CTU Med Research Council; Overport
  • Durban, South Africa
    • South African MRC HIV CTU Med Research Council; R.K. Khan Hospital
  • Durban, South Africa
    • South African MRC HIV CTU Med Research Council; Tongaat
  • Durban, South Africa
    • South African MRC HIV CTU Med Research Council; Umkomaas
  • Durban, South Africa
    • South African MRC HIV CTU Med Research Council; Verulam
  • Gauteng
    • Johannesburg, Gauteng, South Africa, 2001
      • Wits Reproductive Health Institute (WRHI)
  • Guateng
    • Johannesburg, Guateng, South Africa, 2193
      • CAPRISA-The Aurum Institute
  • KwaZulu Natal
    • Durban, KwaZulu Natal, South Africa, 4001
      • CAPRISA eThekwini
  • Soweto
    • Johannesburg, Soweto, South Africa, 1804
      • Perinatal HIV Research Unit (PHRU)
• Uganda
  • Kampala, Uganda
    • Makerere University-Johns Hopkins University Collaboration
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • University of Alabama at Birmingham
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15213
      • University of Pittsburgh
• Zimbabwe
  • Seke South
    • Chitungwiza, Seke South, Zimbabwe
      • UZ-UCSF HIV Prevention Trials Unit
  • Spilhaus
    • Harare, Spilhaus, Zimbabwe
      • UZ-UCSF HIV Prevention Trials Unit
  • Zengeza
    • Chitungwiza, Zengeza, Zimbabwe
      • UZ-UCSF HIV Prevention Trials Unit

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

The study population will consist of female participants who become or became pregnant during HIV prevention agent trials, or who have or had planned exposures in pregnancy safety studies, and the infants resulting from those pregnancies. Mother participants must still be pregnant, or have had a pregnancy outcome diagnosis less than one year before screening/enrollment, and infant participants must be less than one year old. The study may include HIV-uninfected and -infected participants. Mothers may participate in EMBRACE without participation of their infants; however, infants whose mothers have not enrolled in EMBRACE will not participate.

Description

Inclusion Criteria: Mother cohort

1. Able and willing to provide written informed consent to take part in the study

2. During participation in a parent protocol, has/had a known confirmed pregnancy, meeting at least one of the following sets of criteria in A or B:

   A. Two consecutive monthly study visits, at least 14 days apart, with positive pregnancy tests, in the absence of signs/symptoms of miscarriage or participant report of pregnancy termination.

   B. One or more of the following assessments:

   • Auscultation of fetal heart tones
   • Positive pregnancy test confirmed by clinic staff in the presence of clinically confirmed enlarged uterus
   • Positive pregnancy test confirmed by clinic staff in the presence of missed menses (no menses occurring at least 60 days from the first day of the last menses) by participant report (For amenorrheic or irregularly cycling women, two consecutive positive hCG tests (criterion A) or any of the other clinical signs of pregnancy included under the criteria B listing will be used to confirm MTN-016 eligibility).
   • Clinical assessment of fetal movement
   • Demonstration of pregnancy by ultrasound
3. Able and willing to provide adequate locator information, as defined in site SOPs

Note: Participants do not have to be currently enrolled or engaged in follow-up in a parent protocol to participate in EMBRACE.

Inclusion Criteria: Infant cohort

1. Has written informed consent provided by parent(s)/guardian to take part in the study in a manner consistent with local standards, site Institutional Review Board (IRB) guidance and the US Code of Federal Regulations (CFR)
2. Born to EMBRACE participant mother from pregnancy concurrent with participation in parent study

Exclusion Criteria: Mother cohort

1. Has any condition that in the opinion of the investigator or designee, would complicate interpretation of study outcome data, make participation in the study unsafe, or otherwise interfere with achieving the study objectives
2. Pregnancy outcome occurred greater than one year ago

Exclusion Criteria: Infant cohort

1. Has any condition that, in the opinion of the investigator or designee, would complicate interpretation of study outcome data, make participation in the study unsafe, or otherwise interfere with achieving the study objectives
2. Has reached 1 year birth date

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Pregnant Women; Pregnant women exposed to an HIV prevention study agent during pregnancy
Infant; Infants resulting from pregnancies where there exists maternal HIV prevention agent exposure

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pregnancy and delivery outcomes comparison	To compare adverse pregnancy and delivery outcomes between participant mothers assigned to an active agent with those of mothers assigned to placebo/control. Pregnancy and delivery outcomes of interest are: delivery prior to 37 completed weeks of gestation; stillbirth or intrauterine fetal demise (≥ 20 weeks); spontaneous abortion (< 20 weeks); ectopic pregnancy; intrapartum hemorrhage; postpartum hemorrhage; non-reassuring fetal status; chorioamnionitis; hypertensive disorders of pregnancy; gestational diabetes; intrauterine growth restriction	Duration of Study
Major malformations comparison	To compare the prevalence of major malformations identified in the first year of life between infants of mothers assigned to an active agent with those of infants of mothers assigned to placebo/control. Major malformations are defined as structural abnormalities with surgical, medical, or cosmetic importance.	Duration of Study

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Infant growth parameters comparison	To compare growth parameters in the first year of life between infants of mothers assigned to an active agent with those of mothers assigned to placebo/control. Growth parameters of interest are weight, length, and head circumference at birth, one month, six months and 12 months.	Duration of Study
HIV drug resistance mutations comparison	2. To evaluate the prevalence and persistence of HIV drug resistance mutations in plasma among HIV-infected infants.	Duration of Study

Collaborators and Investigators

• Sponsor: Microbicide Trials Network
• Collaborators: National Institute of Allergy and Infectious Diseases (NIAID); Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
• Investigators: Study Chair: Richard Beigi, MD, Microbicide Trials Network

Publications and helpful links

General Publications

• Makanani B, Balkus JE, Jiao Y, Noguchi LM, Palanee-Phillips T, Mbilizi Y, Moodley J, Kintu K, Reddy K, Kabwigu S, Jeenariain N, Harkoo I, Mgodi N, Piper J, Rees H, Scheckter R, Beigi R, Baeten JM. Pregnancy and Infant Outcomes Among Women Using the Dapivirine Vaginal Ring in Early Pregnancy. J Acquir Immune Defic Syndr. 2018 Dec 15;79(5):566-572. doi: 10.1097/QAI.0000000000001861.
• Mhlanga FG, Noguchi L, Balkus JE, Kabwigu S, Scheckter R, Piper J, Watts H, O'Rourke C, Torjesen K, Brown ER, Hillier SL, Beigi R. Implementation of a prospective pregnancy registry for antiretroviral based HIV prevention trials. HIV Clin Trials. 2018 Feb;19(1):8-14. doi: 10.1080/15284336.2017.1411419. Epub 2017 Dec 21.

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2009
• Primary Completion (Actual): May 6, 2020
• Study Completion (Actual): May 6, 2020

Study Registration Dates

• First Submitted: September 23, 2010
• First Submitted That Met QC Criteria: September 24, 2010
• First Posted (Estimate): September 27, 2010

Study Record Updates

• Last Update Posted (Actual): June 21, 2021
• Last Update Submitted That Met QC Criteria: June 17, 2021
• Last Verified: June 1, 2021

More Information

Terms related to this study

• Keywords: HIV; Pregnancy; Infant; Mother; malformations; Chemoprophylactic Exposure
• Other Study ID Numbers: MTN-016; 3UM1AI068633 (U.S. NIH Grant/Contract); 10737 (DAIDS Protocol ID)