Research Project
9054145
DESCRIPTION (provided by applicant): Increasing numbers of infants are born to HIV infected mothers who receive combination antiretroviral treatment (ART) from before or early pregnancy. Although such treatment benefits the mother and reduces the risk of mother-to-child transmission (MTCT) to very low levels, there is some evidence showing an increased risk of preterm delivery associated with highly active ART (HAART) from early pregnancy, possibly due to altered immune environment in late pregnancy. Preterm birth is a significant contributory factor for infant mortality is associated with morbidity in the first years of life and may have significant long-term consequences for child development, educational attainment, and quality of life. An increased risk of preterm delivery associated with HAART would potentially be a considerable burden in countries in sub-Saharan Africa which face the largest burden of HIV. It is therefore critical to understand the factors leading to preterm delivery, and to understand the underlying biological mechanisms, in order to develop interventions to reduce preterm delivery from occurring. We aim to estimate the risk of premature delivery using data from a rural government prevention of mother-to-child programme, for which we have developed and host the database, to explore associated clinical and socio-demographic factors in a cohort of approximately 880 HIV-1-infected and 1320 uninfected women. We will follow up the mothers and infants for two years, with further contacts at 3 and 4 years of age, in the clinic-setting and assess the family environment using routinely collected data from the ongoing population-based surveillance in which these mother-child pairs participate. We will investigate possible immunological correlates of preterm delivery in 248 HIV- 1-infected women (of whom about 15% will be on HAART from before pregnancy and the remainder initiated at the first antenatal visit); we expect about 9 premature deliveries in the group on HAART pre-pregnancy and 58 in those initiating HAART in pregnancy and will assess their blood samples in comparison with those from 58 age- and HIV progression-matched controls. This project would contribute to knowledge by (i) quantifying the association between HAART used to reduce MTCT, preterm delivery rates and neonatal and infant health in northern KwaZulu-Natal, South Africa (a low resource area with high HIV prevalence), (ii) testing the hypothesis that immune deregulations occurring during immune reconstitution under HAART lead to preterm delivery and iii) exploring the longer-term impact on the child and the family. Our findings will contribute importantly to the understanding of the biological mechanisms leading to preterm delivery, and longer term consequences, will inform policy, and eventually save lives.
