UNCPM 22314 - Pregnancy, Infant and Maternal Health Outcomes Study

NCT ID: NCT06158126

Last Updated: 2025-03-14

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE4
• Total Enrollment: 621 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-04-17
• Study Completion Date: 2027-12-31

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.

Detailed Description

For the prospective safety cohort, the study will enroll and follow up eligible women attending antenatal clinic and planning to deliver at Bwaila District Hospital in Lilongwe, Malawi. The primary objective is comparing composite adverse pregnancy events (spontaneous miscarriage, stillbirth, preterm birth, or infant born small for gestational age) between women using CAB-LA and those using oral PrEP. Pregnant women assessed as being at substantial risk for HIV and eligible for PrEP per Malawi national guidelines will be included. Infants will be followed alongside their mothers.

All women meeting eligibility criteria will be consented and offered PrEP (if not already taking it). Women will have access to either CAB-LA or oral PrEP and will be given an opportunity to choose one option. For the Safety Cohort, researchers will group women according to use of oral PrEP (FTC/TDF or TDF/3TC) versus injectable PrEP (CAB-LA), and according to PrEP use before or after pregnancy diagnosis as follows:

Group 1a: Initiating daily oral PrEP during pregnancy Group 1b: Using daily oral PrEP at the time of pregnancy diagnosis Group 2a: Initiating injectable CAB-LA during pregnancy Group 2b: Using injectable CAB-LA at the time of pregnancy diagnosis.

Follow-up contacts for the mother-infant pairs will follow the Malawi ANC package schedule of events during pregnancy, and then include a delivery/birth visit and a series of postpartum visits through week 52 (exit visit). Interim visits initiated by the study could be to repeat abnormal laboratory tests or for safety monitoring of an adverse event. Interim visits initiated by the participant could be to report an adverse event or to seek primary care. Visits will include a series of clinical and laboratory procedures to monitor and assess any pregnancy, maternal health, or infant adverse outcomes. All clinical and laboratory adverse events will be accessed and graded using the Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events. These follow up visits will also optimize antenatal care per the Malawi ANC package.

Clinical and sociodemographic data with be collected by the clinic staff at the UNC study site at Bwaila District Hospital. Quantitative methods will involve administration of brief behavioral surveys conducted every six months during the study follow up period. The surveys will include (but not be limited to) questions about women's attitudes and beliefs about the two PrEP options, and questions about product-related choice and preferences. Surveys will also include risk questionnaire collecting information about previous sexual activity, partners, and PrEP use over the preceding six months, as well as self-perception of HIV risk.

As part of the mixed methods approach, researchers will also conduct qualitative interviews with women to further assess acceptability of oral PrEP or CAB-LA at enrollment, 6 weeks postnatal, and study exit. This component will include a series of in-depth interviews (IDIs) with a subset of women from each group, as well as IDIs with a subset of women who experience adverse obstetric outcomes and those who seroconvert while on injectable or oral PrEP. The aim is to assess whether there are changes in the perceptions and acceptability of oral PrEP or CAB-LA over the study period and explore women's views about future PrEP use during pregnancy and breastfeeding and their choices to use PrEP with subsequent pregnancies.

Additionally, all women in the safety cohort will be enrolled into a PrEP in Pregnancy Registry. The registry in this study will contribute to the development of a national PrEP Pregnancy Registry and subsequent registration and longitudinal surveillance of eligible women without HIV at CAB-LA early access sites in Blantyre and Lilongwe. The registry will include all women initiating PrEP in the national program while pregnant or at the time of diagnosis of pregnancy, and those who become pregnant while on PrEP.

Registry administrators (RAs) at PrEP sites, who may be community health workers, nurses or midwives working at these sites, will register pregnant women into the PrEP Pregnancy Registry as part of routine data collection. The RA's will then obtain basic health information at enrollment, and conduct a follow-up visit at or following delivery to collect pregnancy outcomes and health care provided during delivery. These activities will be conducted as part of routine care.

Conditions

Pre-exposure Prophylaxis; HIV Prevention; Pregnancy Related

Study Design

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

Study Groups

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

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.

Group Type: ACTIVE_COMPARATOR

Initiating daily oral PrEP during pregnancy

Intervention Type: DRUG

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

Already using daily oral PrEP at the time of pregnancy diagnosis

Intervention Type: DRUG

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

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

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.

Group Type: EXPERIMENTAL

Initiating injectable PrEP during pregnancy

Intervention Type: DRUG

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

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

Intervention Type: DRUG

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

Interventions

Initiating daily oral PrEP during pregnancy

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

Intervention Type: DRUG

Already using daily oral PrEP at the time of pregnancy diagnosis

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

Intervention Type: DRUG

Initiating injectable PrEP during pregnancy

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

Intervention Type: DRUG

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

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

Intervention Type: DRUG

Other Intervention Names

Tenofovir disoproxil fumarate (TDF)/emtricitabine (FTC) or lamivudine (3TC) (FTC/TDF or TDF/3TC); Tenofovir disoproxil fumarate (TDF)/emtricitabine (FTC) or lamivudine (3TC) (FTC/TDF or TDF/3TC); CAB-LA; CAB-LA

Eligibility Criteria

Inclusion Criteria

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.

Exclusion Criteria

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.

• Minimum Eligible Age: 15 Years
• Maximum Eligible Age: 55 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: Yes

Sponsors

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

NIH

Sponsor Role: collaborator

United States President's Emergency Plan for AIDS Relief

FED

Sponsor Role: collaborator

Ministry of Health, Malawi

OTHER_GOV

Sponsor Role: collaborator

University of North Carolina, Chapel Hill

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Friday Saidi, MBBS, MMED

Role: PRINCIPAL_INVESTIGATOR

UNC Project Malawi

Locations

Bwaila Distict Hospital

Lilongwe, , Malawi

Site Status: RECRUITING

Countries

Malawi

Central Contacts

Charity Nakanga, MBBS, MSc

Role: CONTACT

cnakanga@unclilongwe.org

265 88 556 5888

References

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.

Reference Type: DERIVED

PMID: 39334032 (View on PubMed)

Other Identifiers

1P01HD112215

Identifier Type: NIH

Identifier Source: secondary_id

View Link

23-2220

Identifier Type: -

Identifier Source: org_study_id