Clinical trial NCT06158126: UNCPM 22314 - Pregnancy, Infant and Maternal Health Outcomes Study
Official title: UNCPM 22314 - Evaluating the Safety of Pregnancy, Infant and Maternal Health Outcomes Among PrEP Users in Malawi
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Pre-exposure Prophylaxis
HIV Prevention
Pregnancy Related
Keywords: PrEP
Pregnancy
Breastfeeding
Infant health
HIV prevention
Maternal health
Eliminating mother-to-child transmission (EMTCT)
Lead sponsor: University of North Carolina, Chapel Hill
Sponsor class: OTHER
Collaborators: name: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
name: United States President's Emergency Plan for AIDS Relief
name: Ministry of Health, Malawi
First posted: 2023-12-06
Enrollment: 621
Sex: FEMALE
Minimum age (years): 15
Maximum age (years): 55
Standard ages: CHILD
ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

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.

Primary outcomes:
measure: Rate of composite adverse pregnancy outcomes
timeFrame: Enrollment through birth
Secondary outcomes:
measure: Proportion of women developing grade 3 or higher clinical or laboratory events
timeFrame: Enrollment through 52 weeks postpartum
measure: Proportion of infants developing stage 3 or higher clinical or laboratory events
timeFrame: Birth through 52 weeks of life
measure: Proportion of infants born with congenital anomalies
timeFrame: Birth through 52 weeks of life
measure: Number of infants who are underweight
timeFrame: Birth through 52 weeks of life
measure: Proportion of infants who are underweight
timeFrame: Birth through 52 weeks of life
measure: Number of infants who are stunted
timeFrame: Birth through 52 weeks of life
measure: Proportion of infants who are stunted
timeFrame: Birth through 52 weeks of life
measure: Number of infants who have moderate or severe acute malnutrition
timeFrame: Birth through 52 weeks of life
measure: Proportion of infants who have moderate or severe acute malnutrition
timeFrame: Birth through 52 weeks of life
measure: Number of infants with poor neurodevelopment outcomes
timeFrame: Birth through 52 weeks of life
measure: Acceptability of oral PrEP or CAB-LA
timeFrame: Delivery through 52 weeks postpartum
measure: Adoption of PrEP in Pregnancy Registry
timeFrame: 6 to 24 months after implementation
measure: Reach of PrEP in Pregnancy Registry
timeFrame: 6 to 24 months after implementation
measure: Fidelity to PrEP in Pregnancy Registry
timeFrame: 6 to 24 months after implementation
Other outcomes:
Locations:
city: Lilongwe
country: Malawi
facility: Bwaila Distict Hospital
Study officials:
affiliation: UNC Project Malawi
name: Friday Saidi, MBBS, MMED
role: PRINCIPAL_INVESTIGATOR
References: