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

external supervisor

Professor Philippe Guerin, Nuffield Department of Medicine

background

1.3 million HIV-positive pregnant women 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 (WHO) 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. 

In 2016, we published a large systematic review and meta-analysis in Lancet HIV, which showed that ART-naïve maternal HIV-infection is associated with an increased risk of preterm birth (PTB, less than 37 weeks), small-for-gestational-age (SGA, less than 10^th centile), low birthweight (LBW, less than 2500g) and stillbirth. We have further shown that HIV-positive pregnant women receiving effective ART remain at higher risk of adverse pregnancy outcomes, compared to HIV-negative women. This appears to be particularly true for ART regimens containing protease inhibitors. Moreover, preconception ART initiation may be associated with higher risks of adverse outcomes. However, a major limitation of previous meta-analyses of cohort studies is the potential for confounding. 

Key references:

Wedi et al Hemelaar, Lancet HIV, 3:e33-48(2016)

Tshivuila-Matala et al Hemelaar, AIDS, 34(11):1643-56(2020)

Cowdell et al Hemelaar, EClinicalMedicine, 46:101368 (2022)

Portwood et al Hemelaar, AIDS, 36(10):1409-27 (2022)

Sexton et al Hemelaar, HIV Medicine, doi: 10.1111/hiv.13326 (2022)

Portwood C, et al Hemelaar, AIDS, 37(3): 489-501 (2023)

Portwood C, et al Hemelaar, Frontiers in Medicine, 9: 924593 (2023)

Murray et al Hemelaar, Communications Medicine, 3(1):103 (2023).

RESEARCH EXPERIENCE, RESEARCH METHODS AND TRAINING

The project will encompass a living systematic review of the literature to update our collection of more than 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. Maternal outcomes and child growth and neurodevelopmental outcomes may also be examined. Perinatal outcomes associated with pre-exposure prophylaxis (PrEP) use 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 and gynaecology, infectious diseases, statistics or global/public health would be best suited to this project. E The ideal candidate will have a Masters degree in a relevant area (e.g. statistics/epidemiology/public health). The project has a broad scope and candidates are encouraged to contact Dr Joris Hemelaar to work out a specific project proposal.