Pregnancy and Neonatal Outcomes Following Antenatal Exposure to Raltegravir: a Pooled Analysis From the European Pregnancy and Paediatric Infections Cohort Collaboration (EPPICC)

Raltegravir is the preferred INSTI for for treatment of antiretroviral-naïve pregnant women in the US Perinatal Guidelines, alongside Dolutegravir, and for late pregnancy. There are relatively limited information available on its use during early pregnancy, particularly the peri-conception period. The aim of the study is to assess "real-world" maternal, fetal and newborn outcomes following RAL use during pregnancy through pooled analysis of individual patient data from observational studies participating in the European Pregnancy and Paediatric Infections Cohort Collaboration.

Study Overview

• Status: Recruiting
• Conditions: HIV Infections
• Intervention / Treatment: Drug: Raltegravir

• Study Type: Observational
• Enrollment (Anticipated): 1200

Contacts and Locations

• Study Contact: Name: Giorgia Dalla Valle; Phone Number: +39 049 821 5447; Email: giorgia.dallavalle@pentafoundation.org

Study Locations

• Belgium
  • Brussels, Belgium
    • Recruiting
    • Centre Hospitalier Universitaire Saint Pierre
• Italy
  • Firenze, Italy
    • Recruiting
    • Università degli studi di Firenze
    • Contact: Luisa Galli
• Romania
  • Bucharest, Romania
    • Recruiting
    • "Victor Babes" Hospital
    • Contact: Luminita Ene
• Russian Federation
  • Arkhangelsk, Russian Federation
    • Completed
    • State Budgetary Institution of Health Protection Irkutsk
  • Saint Petersburg, Russian Federation
    • Completed
    • St Petersburg Republican Hospital
  • Saint Petersburg, Russian Federation
    • Completed
    • St. Petersburg State Budgetary Health Institution
• Spain
  • Barcelona, Spain
    • Recruiting
    • Hospital San Joan de Deu
    • Contact: Claudia Fortuny Guasch; Email: Cfortuny@sjdhospitalbarcelona.org
  • Madrid, Spain
    • Recruiting
    • Hospital Clinico San Carlos
    • Contact: Luis Prieto Tato
• Switzerland
  • Zürich, Switzerland
    • Recruiting
    • University Hospital Zürich
    • Contact: Christian Kahlert
• United Kingdom
  • London, United Kingdom
    • Recruiting
    • University College London
    • Contact: Claire Thorne

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Non-Probability Sample

Study Population

All pregnant women with any exposure to RAL at any time during the pregnancy and their infants will be included in the analysis. With respect to eligibility, we will include any pregnancy reported within the participating studies with any RAL exposure regardless of pregnancy outcome, including those where the pregnancy is still ongoing at the time of the data merger. This analysis will be based on two EPPICC data mergers, one collecting data on eligible pregnancies with estimated date of delivery prior to 2015, and the second collecting data on eligible pregnancies since 2015 (2020/2021 merger).

Description

Inclusion Criteria:

• pregnant women living with HIV, exposed to Raltegravir at any time during the pregnancy participating in EPPICC and their infants.

Exclusion Criteria:

• see inclusion

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
European Pregnancy and Paediatric Infections Cohort Collaboration (EPPICC); Pregnant women living with HIV and their infants from 9 European cohorts and studies within the European Pregnancy and Paediatric Infections Cohort Collaboration (EPPICC)	Drug: Raltegravir; Raltegravir exposure in pregnant women living with HIV in routine clinical care. No study intervention administrated.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Patterns of antenatal use	To describe patterns of antenatal use of RAL-containing regimens, including maternal characteristics, timing of initiation, NRTI backbone/other drugs in regimen and calendar time trends	12 months
Frequency of averse birth outcomes	To describe the frequency of adverse birth outcomes in RAL-exposed pregnancies including birth defects, stillbirths, preterm births, low birth weight infants, and small-for-gestational age infants, by timing of exposure	12 months
Birth defects per trimester of exposure	To compare risk of birth defects in infants with peri-conception and/or first trimester exposure to RAL with that in infants with exposure to RAL from the second or third trimester	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Frequency of discontinuation	To assess the frequency of discontinuation of RAL during pregnancy and potential reasons where data are available.	12 months
Viral suppression	To describe the proportion of women on RAL who achieve viral suppression by the end of pregnancy and the vertical transmission rate in mother-infants pairs with RAL use	12 months

Collaborators and Investigators

• Sponsor: Fondazione Penta UK
• Collaborators: UCL Great Ormond Street Institute of Child Health
• Investigators: Study Chair: Claire Thorne, Professor of infectious disease epidemiology

Study record dates

Study Major Dates

• Study Start (Anticipated): February 20, 2023
• Primary Completion (Anticipated): February 20, 2024
• Study Completion (Anticipated): February 20, 2024

Study Registration Dates

• First Submitted: February 20, 2023
• First Submitted That Met QC Criteria: February 20, 2023
• First Posted (Actual): March 2, 2023

Study Record Updates

• Last Update Posted (Actual): March 2, 2023
• Last Update Submitted That Met QC Criteria: February 20, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Infections; Communicable Diseases; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; HIV Integrase Inhibitors; Integrase Inhibitors; Raltegravir Potassium
• Other Study ID Numbers: Raltegravir

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