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Adverse perinatal outcomes associated with maternal HIV infection and antiretroviral therapy: systematic review and meta-analysis

OPH/22/14

BACKGROUND

1.5 million HIV-positive pregnant women give birth every year, 91% of whom reside in sub-Saharan Africa. Sub-Saharan Africa also has the highest rates of neonatal and child morbidity and mortality, to which adverse perinatal outcomes of pregnancy are major contributors.

In 2016, we published a large systematic review and meta-analysis in Lancet HIV, which showed that antiretroviral therapy (ART)-naïve maternal HIV-infection is associated with an increased risk of preterm birth (PTB, <37 weeks), small-for-gestational-age (SGA, <10th centile), low birthweight (LBW, <2500g) and stillbirth.

The World Health Organization (WHO) recommends ART in pregnancy as it reduces maternal morbidity and mortality, and greatly reduces mother-to-child transmission of HIV. However, it has been controversial whether ART regimens increase the risk of adverse perinatal outcomes, especially PTB.

Key references:

  • Wedi et al Hemelaar, Lancet HIV, 3:e33-48(2016).
  • Tshivuila-Matala et al Hemelaar, AIDS, 34(11):1643-1656(2020).

RESEARCH EXPERIENCE, RESEARCH METHODS AND TRAINING

The project will encompass a living systematic review of the literature to update our collection of >130 papers describing the associations between maternal HIV infection and antiretroviral therapy and 12 specific adverse perinatal outcomes, such as PTB and SGA. Data will be extracted and quality assessments of studies performed. Data will be aggregated using (network) meta-analysis methods. Sensitivity and subgroup analyses will be conducted.

The association between HIV/ART and specific perinatal outcomes will be dissected by examining the role of different types of ART, including i) regimen complexity (monotherapy vs triple therapy), ii) classes of drugs (protease inhibitors, integrase inhibitors, NRTIs and NNRTIs), and iii) timing of ART initiation (preconception vs antenatal initiation).

These analyses can be further expanded to include burden of disease analyses and cost-benefit analyses. Individual patient data (IPD) may be requested from study authors to allow IPD meta-analyses and enable correction for potential confounding factors. Maternal outcomes associated with HIV/ART may also be examined.

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, including meta-analysis methodology training, will be provided in Oxford.

PROSPECTIVE STUDENT

A student with a background in medicine, obstetrics & gynaecology, infectious diseases, statistics or global health might suit this project. A successful candidate will have experience in and enthusiasm for evidence synthesis through systematic reviews and meta-analysis. 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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