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.
