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An “omics” approach to investigate adverse perinatal outcomes in HIV-positive women

OPH/22/12

EXTERNAL SUPERVISOR

Prof Roman Fisher, Nuffield Department of Medicine

Background

Antiretroviral therapy (ART)-naïve maternal HIV-infection is associated with an increased risk of preterm birth (<37 weeks), small-for-gestational-age (<10th centile), low birthweight (<2500g) and stillbirth. ART in pregnancy reduces maternal morbidity and mortality, and greatly reduces mother-to-child transmission of HIV, but may increase the risk of adverse perinatal outcomes.

We previously conducted a prospective pregnancy cohort study in Soweto, South Africa where we found that adverse perinatal outcomes were more common among HIV-positive women on ART compared to HIV-negative women. The biological mechanisms responsible for these increased rates of adverse perinatal outcomes associated with maternal HIV/ART are unknown.

Key references:

  • Akoto et al Hemelaar, Scientific Reports, 11(1):10079(2021).
  • Akoto et al Hemelaar, Scientific Reports, 10(1):13265(2020).
  • Akoto et al Hemelaar, PLoS One, 15(6):e0235162(2020).
  • Ravi et al Hemelaar, Am J Reprod Immunol, 83(6):e13240(2020).

RESEARCH EXPERIENCE, RESEARCH METHODS AND TRAINING

The project will encompass “omics” analysis of blood samples already collected from 94 HIV-positive and 104 HIV-negative women in the South African pregnancy cohort. Samples were collected in each trimester of pregnancy, as well as at delivery and postnatally, resulting in 517 samples in total.

Proteomics and metabolomics analysis of plasma samples will be performed in the Target Discovery Institute in Oxford. Transcriptomics analysis of peripheral blood mononuclear cells will be performed in collaboration with the Wellcome Centre for Human Genetics in Oxford. Integrated pathway analysis will be performed with the Molecular Analytics research group in the Big Data Institute.

The aim is to identify molecular signatures associated with specific adverse perinatal outcomes, such as preterm birth and small-for-gestational-age, in HIV-positive and HIV-negative women. All comparisons of maternal blood samples will be conducted separately for each trimester and will be analysed longitudinally over the course of pregnancy.

Specific objectives:

  1. Discover biomarkers predictive of adverse perinatal outcomes.
  2. Elucidate molecular mechanisms underlying adverse perinatal outcomes.
  3. Identify targets for preventative and therapeutic interventions.

FIELD WORK, SECONDMENTS, INDUSTRY PLACEMENTS AND TRAINING

It is anticipated that the work will be conducted in Oxford and all necessary facilities, equipment and training relating to proteomics, metabolomics and transcriptomics, as well as the statistical analysis, will be provided in Oxford.

PROSPECTIVE STUDENT

A student with a background in medicine, biochemistry, biology, infectious diseases, statistics or global health might suit this project. A successful candidate will have experience in ‘omics’ and statistical analysis and modeling. The project has a broad scope and candidates are encouraged to contact Dr Joris Hemelaar to work out a specific project proposal.

Supervisors

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