Adverse perinatal outcomes associated with antiretroviral therapy for HIV: systematic review and individual participant data meta-analysis

Background

1.1 million pregnant women living with HIV (WLHIV) give birth every year, 91% of whom reside in sub-Saharan Africa, which also has the highest rates of neonatal and child morbidity and mortality. The World Health Organization recommends antiretroviral therapy (ART, triple antiretroviral drugs) in pregnancy as it reduces maternal morbidity and mortality, and greatly reduces mother-to-child transmission of HIV.

We have published several large systematic reviews and meta-analyses describing the associations between maternal HIV and ART regimens with adverse perinatal outcomes. This work showed that 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. We have further shown that pregnant WLHIV receiving effective ART remain at higher risk of adverse pregnancy outcomes, compared to HIV-negative women, irrespective of the ART regimen or the timing of ART initiation. However, a major limitation of previous meta-analyses of cohort studies is the potential for confounding.

research experience, research methods and skills training

The project will encompass a systematic review of the literature to update our collection of >130 papers describing the associations between maternal HIV/ART and 12 specific adverse perinatal outcomes, such as PTB and SGA.

Individual participant data (IPD) will be requested from study authors to allow IPD meta-analyses and enable correction for potential confounding factors. 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 containing different classes of drugs (protease inhibitors, integrase inhibitors, NRTIs and NNRTIs), as well as specific drugs. Importantly, data on novel ART regimens in pregnancy, such as dual drug regimens and long-acting injectables, will be sought.

Maternal outcomes and child growth and neurodevelopmental outcomes may also be examined. Perinatal outcomes associated with pre-exposure prophylaxis (PrEP) use, including oral PrEP and long-acting injectables, in HIV-negative pregnant women may also be examined.

These studies aim to inform international treatment guidelines.

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/public health would be best suited to this project.

The ideal candidate will have a Masters degree in a relevant field. The project has a broad scope and candidates are encouraged to contact Prof Joris Hemelaar to work out a specific project proposal.