Using linked HIV observational patient level databases to examine risk for and outcome of maternal HIV infection

In the UK today only ~1% of diagnosed HIV-positive pregnant women pass on HIV to their babies, mainly thanks to the use of "drug cocktails" of anti-HIV drugs. Research is needed to improve our management of HIV-positive pregnant women, particularly as the population of HIV-positive pregnant women is changing, as well as the types of drugs used. Despite their beneficial effects, concerns remain about the safety of taking anti-HIV drugs in pregnancy, for example there appears to be an increased chance of giving birth prematurely. Some anti-HIV drugs cause cancer in animals, but long-term health consequences for HIV-negative children exposed to anti-HIV drugs before birth are uncertain. We plan to investigate these issues in management and safety by analysing data from the UK and Ireland National Study of HIV in Pregnancy and Childhood, which collects information on all diagnosed HIV-positive pregnant women and their babies. To investigate possible long-term adverse consequences of exposure to anti-HIV drugs before birth, we plan to develop our linkage of Study data with other sources of health information. The project results will be important for HIV-positive women, their doctors and health care planners and should help improve management of HIV-positive pregnant women and their children.

Management of HIV disease is particularly complex in pregnancy, as maternal health needs, the pregnancy itself and the developing fetus all need consideration. Combination antiretroviral therapy (ART), highly effective for preventing HIV disease progression and mother-to-child transmission (MTCT), is widely used in pregnancy despite a lack of robust and long-term safety data. Research is needed to address how best to use cART safely, effectively and appropriately in pregnancy, particularly among emerging groups (including women with complex treatment histories, coinfections, vertically-acquired infection). The aim of this project is to address such contemporary questions central to clinical practice and to public health, and to improve the scientific basis for HIV prevention, diagnosis and optimal management of pregnant women and their infants. This will be achieved through analysis of data collected through the National Study of HIV in Pregnancy and Childhood (NSHPC), a comprehensive dataset of all pregnancies in the UK and Ireland in women with diagnosed HIV infection with ~1600 pregnancies reported annually, and through record linkage within the UK Platform for Integrated Clinical & Research Data in HIV (known as DHICE) and with the NHS Information Centre and ONS. The objectives are: 1) to characterize the contemporary population of HIV-positive pregnant women; 2) to quantify rates of MTCT, explore risk factors for transmission, including drug resistance and coinfections, and examine the use of therapeutic and obstetric interventions to prevent MTCT in newly diagnosed HIV-infected pregnant women and in women with established diagnosis; 3) to investigate adverse pregnancy outcomes among HIV-positive pregnant women and their associations with ART and 4) to evaluate the long-term safety of fetal and neonatal exposure to HIV and ART in uninfected individuals through "flagging" and data linkage.

The proposed fellowship would add value and have impact in the following ways:

Research capacity building - the clinical fellow would receive training in epidemiology and statistics and complete a PhD (or possibly MD) and thus the potential in the future to follow an academic clinical epidemiologist career path.

Publications - it is expected that a substantial number of research outputs would emanate from the fellowship, including conference abstracts (at least six) and publications (at least three) in peer-reviewed academic journals.

Influence on policy and practice - the NSHPC actively engages in policy and services processes, both in the UK and internationally, and has close links with the British HIV Association (BHIVA) and the UK National Screening Committee. Findings from the study are cited in national and international clinical guidelines and policy documents and it is expected that new findings from the proposed project would also contribute to such guidance.

Dissemination to non-academic audiences - the fellow would be in the position to present research findings to clinicians at meetings such as those held regularly by BHIVA, the Children's HIV Association (CHIVA) and the London HIV Pregnancy Research Group; the NSHPC has good links to patient organisations such as i-Base, Positively UK and Body & Soul and dissemination of findings would occur within these groups too.