High risk pregnancies in women living with HIV in Europe

Background:
Worldwide there have been successes in the prevention of vertical transmission of HIV, for example with 82% of the approximately 1.5 million pregnant women with HIV receiving antiretroviral therapy (ART) (2018 data). In Europe, vertical transmission rates are very low on a population level, e.g. in the UK this is now around 3 per 1000. This reflects a combination of factors, including earlier HIV diagnosis, very high ART coverage (most pregnant women already on suppressive regimens at conception) and earlier start of ART in pregnancy for women not on treatment at conception (1,2). However, even in settings with very low vertical transmission rates, there remains a subgroup of high risk pregnancies where the infant is particularly susceptible to vertical infection. Understanding more about the circumstances leading up to new vertical infections is key to developing strategies to prevent them. Interventions to reduce risk of VT in such high-risk situations include augmenting antenatal ART with potent drugs that rapidly cross the placenta and use of combination neonatal prophylaxis. The most important factors underlying high risk pregnancies relate to antenatal ART and/or uncontrolled viraemia, and include lack of or late start of ART in pregnancy (linked in turn to no or late antenatal care) and non-adherence to ART; drug resistance may also play a part. Another important sub-group within the high risk pregnancies are women who become HIV infected during pregnancy (3). The public health goal is for women living with HIV to deliver healthy infants, free of HIV. There is increasing evidence in Europe indicating that women with HIV have worse perinatal outcomes than uninfected women, including higher risk of stillbirth (4). A better understanding of the specific risks faced by the contemporary population of pregnant women with HIV, alongside monitoring of the impact of changes in policies and practices, is needed to optimise their health and that of their infants.

Aims/Objectives:
The objectives of this PhD will be to (1) identify and characterise the main high risk groups among pregnant women living with HIV in European settings with respect to adverse pregnancy, birth and/or neonatal outcomes; (2) describe these outcomes and their associated risk factors; and (3) investigate the clinical management (e.g. use of interventions to reduce vertical transmission) including differences within and between countries. This real world evidence will be used to inform public health recommendations and clinical guidelines.

Methods:
This PhD will use datasets from the European Pregnancy and Paediatric Infections Cohort Collaboration (EPPICC), an international network of cohort and surveillance studies. EPPICC conducts epidemiological research on pregnant women living with HIV and their children, with a focus on scientific and clinical management-related questions requiring a large sample size of patients which the contributing studies cannot answer individually. Participating studies include multisite cohorts with national or sub-national coverage, single-site cohorts and surveillance studies. They periodically provide pseudonymised individual patient data prepared according to a data specification based on a modified HIV Data Exchange Protocol to the epidemiological coordinating centre at GOSICH. Individual cohort/study datasets are then merged, and analyses conducted on the pooled dataset. The 2015 data merger included >33,000 pregnancies from 11 countries for the period 2002-2015, and a 2021 merger is ongoing.

References:
1.  Peters H et al, 2017. Mother-to-Child HIV Transmission Rates Continue to Decline: 2012-2014. Clinical Infectious Diseases, 64, 527-528.
2.  Mandelbrot L. et al 2015. No perinatal HIV-1 transmission from women with effective antiretroviral therapy starting before conception. Clin Infect Dis, 61, 1715-25.
3.  Drake AL et al 2014. Incident HIV during pregnancy and postpartum and risk of mother-to-child HIV transmission: a systematic review and meta-analysis. PLoS Med, 11, e1001608.
4.  Favarato et al 2019. Stillbirth in Women Living With HIV Delivering in the United Kingdom and Ireland: 2007-2015, J Acquir Immune Defic Syndr; 82(1):9-16