MARVAL Study

This South African MRC and UKRI funded study will explore the link between the use of ART and increased risks of adverse birth outcomes, including pre-term birth delivery for the mother (PTD)/Pre-term birth for the child (PTB) and low birth-weight which significantly contributes to neurodevelopmental and lung defects in these infants. Furthermore, long-term sequalae of PTB include hypertension, type 2 diabetes, metabolic syndrome, heart failure, and ischemic heart disease. HIV and ART have also been associated with increased risk of developing preeclampsia. Recent evidence shows that spontaneous PTD induces immune-vasculopathies in the mother, further expanding its consequences. This study will identify immune networks involved with the interplay between ART, vascular placental development, and adverse birth outcomes. The goal is to identify a mechanistic link between ART, placental development and adverse living-birth outcomes, such as PTB, low birth weight or small for gestational age, as examples. Long term we anticipate that results from this study can be used as a foundation to develop new combinations of existing ARVs, additional treatments and management to mitigate poor health in children.

Our preliminary results show that FXIIIA1, a transglutaminase coagulation factor, is affected by ARV drugs in vitro and ART in pregnant people living with HIV. We hypothesize that Hofbauer cell-derived FXIIIA1 plays a role in angiogenesis in the placenta and this ability is disrupted by different ARV drugs.

Current studies at RIRCA are exploring FXIIIA1 as both a biomarker for placental health and a potential therapeutic target for enhancing placental resilience in compromised pregnancies. This study will help improve our understanding of premature delivery of either appropriate- or small-for-gestational age infants and inform understandings of probable causes.