Association entre la thérapie antirétrovirale et les biomarqueurs de la fonction placentaire pendant la grossesse

Background: HIV infection remains a major public health problem with 2.1 million people newly infected in 2015, including 150,000 children infected mostly in perinatal. With a view to eradicating new infections, since 2012, WHO has recommended that anyone infected with HIV should be on antiretroviral therapy (ART) (concept of "treatment as prevention"). As a result, the majority of HIV-infected women are already on ART at the time of conception and earlier in pregnancy, whereas previously it was mainly initiated in the second trimester of pregnancy. However, some studies have shown an association between the use of ART during pregnancy and perinatal complications (such as premature delivery, low birth weight infants), particularly with protease inhibitor (PI)-based therapies, which could be explained through a role in placental dysfunction. Objective: The aim of this thesis is to measure the association between exposure to ART and placental function in pregnant women. Methods: Clinical and biological data from pregnant women living with HIV recruited between January 2003 and December 2016 in the cohorts of CHU Sainte-Justine (Montreal) and BC Women's Hospital (Vancouver) were used in this study. Placental function was evaluated by the assay of biomarkers used for aneuploidy screening (free human chorionic gonadotropin-free β-hCG, placental plasma protein type A-PAPP-A, alpha-fetoprotein - AFP, unconjugated estriol - uE3, human chorionic gonadotropin - hCG and inhibin-A) and by the assay of angiogenic factors used in preeclampsia screening (PlGF and sFlt-1) in the first and second trimester of pregnancy. The PlGF and sFlt1 assay was performed as an exploratory pilot study on a subset of serum samples stored in the biobank of CHU Sainte-Justine. Each biomarker level (after logarithmic transformation) was compared according to 1) the class of ART and 2) the duration of ART exposure, 3) the time of initiation of ART, using multivariate linear regressions and linear generalized estimating equations adjusted for confounding bias. Results: After adjusting for control variables including race, maternal age, gestational age, body mass index, parity, smoking and sex of the fetus, women receiving ART (whether PI or another class) had significantly increased AFP levels (β = 0.139, 95% CI = [0.055-0.223] iv and β = 0.141, 95% CI = [0.043-0.239] respectively) compared to women who received no treatment. However, there were no significant association between ART type, whether IPbased or not, and the level of PAPP-A, free β-hCG, estriol, total hCG, inhibin A, PlGF and sFlt-1. No significant association was shown between serum biomarker concentration and duration of ART exposure or the time of ART initiation. Conclusion: That study suggests that serum concentration of angiogenic factor and aneuploidy screening biomarkers does not appear to be significantly affected by ART, except for AFP, which increases with exposure to ART regardless of the type (whether PI or other). These observations seem reassuring when considering the use of ART during early pregnancy.

Keyphrases: PAPP-A,, AFP, inhibine-A,, PlGF, sFlt-1, HIV, Pregnancy, Antiretroviral therapy, Placental function, free β-hCG, Unconjucated estriol, Total hCG, inhibin-A