UNCPM 22314 - Pregnancy, Infant and Maternal Health Outcomes Study

NCT06158126 | Recruiting Phase 4

• 2 other identifiers: 23-22201P01HD112215
• Study Type: interventional
• Target: 621
• Locations: 1 country
• Sites: 1

Brief Summary

The primary purpose of this study is to assess the safety of long-acting injectable cabotegravir (CAB-LA) and oral pre-expose prophylaxis (PrEP) (FTC/TDF or 3TC/TDF) for the prevention of HIV during pregnancy and breastfeeding among pregnant women and their infants in Malawi. The main question the study aims to answer is: \- Do composite adverse pregnancy events, maternal health outcomes, and/or infant health outcomes differ between individuals taking oral PrEP and those taking CAB-LA? Women who are already using PrEP at the time of pregnancy diagnosis or those who initiate PrEP during pregnancy will enroll into a Safety Cohort where they will be closely followed up during pregnancy while optimizing their antenatal care (ANC) per the Malawi ANC package. Women will have access to either CAB-LA or oral PrEP and will be given an opportunity to choose one option. Women and their infants will attend a series of follow-up visits through pregnancy, birth, and the postnatal period. In addition, the study will contribute to the development of a national PrEP Pregnancy Registry which will be initially rolled out in Lilongwe and Blantyre -the two most populous cities in Malawi-before a nationwide roll out begins under the guidance of the Malawi Ministry of Health.

Conditions

Pre-exposure Prophylaxis; HIV Prevention; Pregnancy Related

Keywords

PrEP; Pregnancy; Breastfeeding; Infant health; HIV prevention; Maternal health; Eliminating mother-to-child transmission (EMTCT)

Outcome Measures

Primary Outcomes (1)

• Rate of composite adverse pregnancy outcomes

  Rate will be calculated as the number of women with an adverse pregnancy outcome, defined as the occurrence of any one of the following events: spontaneous miscarriage (pregnancy lost before 28 weeks gestation), stillbirth (fetal death at or after 28 weeks gestation), preterm birth (delivery before 37 weeks gestation), infant born small for gestational age (birth weight of less than 10th percentile for gestational age) over the accumulated person time from enrollment through birth.

  Enrollment through birth

Secondary Outcomes (14)

• Proportion of women developing grade 3 or higher clinical or laboratory events

  Enrollment through 52 weeks postpartum

• Proportion of infants developing stage 3 or higher clinical or laboratory events

  Birth through 52 weeks of life

• Proportion of infants born with congenital anomalies

  Birth through 52 weeks of life

• Number of infants who are underweight

  Birth through 52 weeks of life

• Proportion of infants who are underweight

  Birth through 52 weeks of life

Study Arms (2)

Oral PrEP (FTC/TDF or TDF/3TC) during pregnancy

ACTIVE COMPARATOR

The arm will include pregnant women who have met eligibility criteria, consented, and chosen to initiate or remain on oral PrEP (FTC/TDF or TDF/3TC) during pregnancy. Within the arm, they will be grouped according to whether they started oral PrEP before or after pregnancy diagnosis. All participants will continue to be offered oral PrEP throughout the study and will be followed up for the duration of the study. All women will be registered into the PrEP Pregnancy Registry as part of routine care.

Drug: Initiating daily oral PrEP during pregnancy; Drug: Already using daily oral PrEP at the time of pregnancy diagnosis

Long-acting injectable cabotegravir (CAB-LA) during pregnancy

EXPERIMENTAL

The arm will include pregnant women who have met eligibility criteria, consented, and chosen to initiate or remain on injectable PrEP (CAB-LA) during pregnancy. Within the arm, they will be grouped according to whether they started CAB-LA before or after pregnancy diagnosis. All participants will continue to be offered CAB-LA throughout the study and will be followed up for the duration of the study. All women will be registered into the PrEP Pregnancy Registry as part of routine care.

Drug: Initiating injectable PrEP during pregnancy; Drug: Already using injectable PrEP (CAB-LA) at the time of pregnancy diagnosis

Interventions

Initiating daily oral PrEP during pregnancy DRUG

Group 1a will include pregnant women who initiate oral PrEP when already pregnant, at enrollment into the study.

Also known as: Tenofovir disoproxil fumarate (TDF)/emtricitabine (FTC) or lamivudine (3TC) (FTC/TDF or TDF/3TC)

Oral PrEP (FTC/TDF or TDF/3TC) during pregnancy

Already using daily oral PrEP at the time of pregnancy diagnosis DRUG

Group 1b will include women already using daily oral PrEP at the time of pregnancy diagnosis and enrollment in the study.

Also known as: Tenofovir disoproxil fumarate (TDF)/emtricitabine (FTC) or lamivudine (3TC) (FTC/TDF or TDF/3TC)

Oral PrEP (FTC/TDF or TDF/3TC) during pregnancy

Initiating injectable PrEP during pregnancy DRUG

Group 2a will include pregnant women who initiate injectable PrEP (CAB-LA) when already pregnant, at enrollment into the study.

Also known as: CAB-LA

Long-acting injectable cabotegravir (CAB-LA) during pregnancy

Already using injectable PrEP (CAB-LA) at the time of pregnancy diagnosis DRUG

Group 2b will include women using injectable PrEP (CAB-LA) at the time of pregnancy diagnosis and enrollment into the study.

Also known as: CAB-LA

Long-acting injectable cabotegravir (CAB-LA) during pregnancy

Eligibility Criteria

• Age: 15 Years - 55 Years
• Gender Eligibility Details: Pregnant women
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Maternal participants:
• Confirmed pregnancy by urine pregnancy test or ultrasound.
• Aged 15 years or older
• PrEP-eligible by Malawi local guidelines
• Confirmed HIV-negative based on the local HIV testing algorithm
• Hepatitis B surface antigen (HBsAg) negative
• Weight \>35 kg
• Provided informed consent and expressed willingness to participate in study activities with their infants.
• Infant participants: Infant participants will enter the study with their mother as unborn infants. There are no specific eligibility criteria for infant participation otherwise.

You may not qualify if:

• Maternal participants will not be eligible to enter the prospective cohort study if any of the following conditions are identified during the screening process:
• Known to be living with HIV
• Known allergies to CAB-LA, TDF/3TC or FTC/TDF
• Other current significant disease process (active or chronic), substance use, or social circumstances that, in the judgment of the site investigator would make participation in the study unsafe.
• Intention to leave the study site's catchment area of Bwaila before scheduled study exit.

Sponsors & Collaborators

• University of North Carolina, Chapel Hill: lead
• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): collaborator
• Ministry of Health, Malawi: collaborator
• United States President's Emergency Plan for AIDS Relief: collaborator

Study Sites (1)

Bwaila Distict Hospital

Lilongwe, Malawi

RECRUITING

Related Publications (1)

• Saidi F, Shah S, Squibb M, Chinula L, Nakanga C, Mvalo T, Matoga M, Bula AK, Chagomerana MB, Kamanga F, Kumwenda W, Mkochi T, Masiye G, Moya I, Herce ME, Rutstein SE, Thonyiwa V, Nyirenda RK, Mwapasa V, Hoffman I, Hosseinipour MC. Evaluating the impact of HIV pre-exposure prophylaxis on pregnancy, infant, and maternal health outcomes in Malawi: PrIMO study protocol. BMC Public Health. 2024 Sep 27;24(1):2604. doi: 10.1186/s12889-024-20029-3.

  PMID: 39334032 DERIVED

MeSH Terms

Conditions

Breast Feeding

Interventions

Tenofovir; Racivir; Lamivudine

Condition Hierarchy (Ancestors)

Feeding Behavior; Behavior

Intervention Hierarchy (Ancestors)

Organophosphonates; Organophosphorus Compounds; Organic Chemicals; Adenine; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Zalcitabine; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Dideoxynucleosides

Study Officials

• Friday Saidi, MBBS, MMED

  UNC Project Malawi

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Charity Nakanga, MBBS, MSc

CONTACT

265 88 556 5888; cnakanga@unclilongwe.org

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 27, 2023
• First Posted: December 6, 2023
• Study Start: April 17, 2024
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2027
• Last Updated: May 5, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Beginning 9 and continuing for 36 months following publication
• Access Criteria: Investigator has approved IRB, IEC, or REB and an executed data use/sharing agreement with UNC

Locations

MA (1)