Cohort profile: Prematurity Immunology in Mothers living with HIV and their infants Study (PIMS)

Prematurity Immunology in Mothers living with HIV and their infants Study (PIMS) is a prospective cohort study in South Africa investigating the association between antiretroviral therapy (ART) use, preterm delivery (PTD) and small-for-gestational age (SGA) live births. PIMS main hypotheses are that ART initiation in pregnancy and ART-induced hypertension are associated with PTD and SGA respectively and that reconstitution of cellular immune responses in women on ART from before pregnancy results in increases in PTD of GA infants.

Pregnant women (n=3972) aged ≥18 years regardless of HIV status recruited from 2015 to 2016 into the overall PIMS cohort (2517 HIV-negative, 1455 living with HIV). A nested cohort contained 551 women living with HIV who were ≤24 weeks' GA on ultrasound: 261 initiated ART before pregnancy, 290 initiated during the pregnancy.

Women in the overall cohort were followed antenatally through to delivery using routine clinical records; further women in the nested cohort were actively followed up until 12 months post partum, with data collected on maternal health (HIV care and ART use, clinical care and intercurrent clinical history). Other procedures conducted on the nested cohort included physical examinations (anthropometry, blood pressure measurement), assessment of fetal growth (ultrasound), maternal and infant phlebotomy for storage of plasma, RNA and peripheral blood mononuclear cells, collection of delivery specimens (placenta and cord blood) and infant 12-month developmental assessment. Preliminary findings have contributed to our understanding of risk factors for adverse birth outcomes, and the relationship between pregnancy immunology, HIV/ART and adverse birth outcomes.

Using specimens collected from study participants living with HIV throughout pregnancy and first year of life, the PIMS provides a valuable platform for answering a variety of research questions focused on temporal changes of immunology markers in women whose immune status is altered by HIV infection, and how ART initiated during the pregnancy affects immune responses. The relationship between these immunological changes with adverse birth outcomes as well as possible longer-term impact of exposure to ART in fetal and early life will be explored. Additionally, further active and passive follow-up of mothers and their infants is planned at school-going age and beyond to chart growth, morbidity and development, as well as changes in family circumstances.