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

Lead Research Organisation: University College London
Department Name: Institute of Child Health

Abstract

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.

Technical Summary

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.

Planned Impact

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.

Publications

10 25 50
 
Guideline Title Recommendations for use of antiretroviral drugs in pregnant HIV-1-infected women for maternal health and interventions to reduce perinatal HIV transmission in the United States
Description Prevention of vertical transmission of HIV
Geographic Reach Multiple continents/international 
Policy Influence Type Citation in clinical guidelines
 
Description BHIVA Science Scholarship
Amount £400 (GBP)
Organisation British HIV Association (BHIVA) 
Sector Charity/Non Profit
Country United Kingdom
Start 04/2015 
End 04/2015
 
Description BHIVA/Janssen Travel Bursary Scholarship
Amount £2,000 (GBP)
Organisation British HIV Association (BHIVA) 
Sector Charity/Non Profit
Country United Kingdom
Start 07/2015 
End 07/2015
 
Description European Pregnancy and Paediatric HIV Cohort Collaboration 
Organisation Bicêtre Hospital
Country France 
Sector Hospitals 
PI Contribution This collaboration carries out pooled analyses and publishes joint papers addressing questions that individual cohorts and studies cannot address individually. We contribute to the scientific leadership as well as contributing data and participating in joint analyses
Collaborator Contribution Access to data and expertise
Impact This collaboration involves obstetricians, infectious diseases specialists, paediatricians, epidemiologists and statisticians.
Start Year 2013
 
Description European Pregnancy and Paediatric HIV Cohort Collaboration 
Organisation Medical Research Council (MRC)
Department MRC Clinical Trials Unit
Country United Kingdom 
Sector Public 
PI Contribution This collaboration carries out pooled analyses and publishes joint papers addressing questions that individual cohorts and studies cannot address individually. We contribute to the scientific leadership as well as contributing data and participating in joint analyses
Collaborator Contribution Access to data and expertise
Impact This collaboration involves obstetricians, infectious diseases specialists, paediatricians, epidemiologists and statisticians.
Start Year 2013
 
Description European Pregnancy and Paediatric HIV Cohort Collaboration 
Organisation National Institutes of Health (NIH)
Department Italian register of HIV infection in children NCBI
Country United States 
Sector Public 
PI Contribution This collaboration carries out pooled analyses and publishes joint papers addressing questions that individual cohorts and studies cannot address individually. We contribute to the scientific leadership as well as contributing data and participating in joint analyses
Collaborator Contribution Access to data and expertise
Impact This collaboration involves obstetricians, infectious diseases specialists, paediatricians, epidemiologists and statisticians.
Start Year 2013
 
Description European Pregnancy and Paediatric HIV Cohort Collaboration 
Organisation Swiss HIV Cohort Study (SHCS)
Country Switzerland 
Sector Academic/University 
PI Contribution This collaboration carries out pooled analyses and publishes joint papers addressing questions that individual cohorts and studies cannot address individually. We contribute to the scientific leadership as well as contributing data and participating in joint analyses
Collaborator Contribution Access to data and expertise
Impact This collaboration involves obstetricians, infectious diseases specialists, paediatricians, epidemiologists and statisticians.
Start Year 2013
 
Description European Pregnancy and Paediatric HIV Cohort Collaboration 
Organisation University of Florence
Country Italy 
Sector Academic/University 
PI Contribution This collaboration carries out pooled analyses and publishes joint papers addressing questions that individual cohorts and studies cannot address individually. We contribute to the scientific leadership as well as contributing data and participating in joint analyses
Collaborator Contribution Access to data and expertise
Impact This collaboration involves obstetricians, infectious diseases specialists, paediatricians, epidemiologists and statisticians.
Start Year 2013
 
Description European Pregnancy and Paediatric HIV Cohort Collaboration 
Organisation University of Padova
Country Italy 
Sector Academic/University 
PI Contribution This collaboration carries out pooled analyses and publishes joint papers addressing questions that individual cohorts and studies cannot address individually. We contribute to the scientific leadership as well as contributing data and participating in joint analyses
Collaborator Contribution Access to data and expertise
Impact This collaboration involves obstetricians, infectious diseases specialists, paediatricians, epidemiologists and statisticians.
Start Year 2013
 
Description European Pregnancy and Paediatric HIV Cohort Collaboration 
Organisation Victor Babes Hospital
Country Romania 
Sector Hospitals 
PI Contribution This collaboration carries out pooled analyses and publishes joint papers addressing questions that individual cohorts and studies cannot address individually. We contribute to the scientific leadership as well as contributing data and participating in joint analyses
Collaborator Contribution Access to data and expertise
Impact This collaboration involves obstetricians, infectious diseases specialists, paediatricians, epidemiologists and statisticians.
Start Year 2013
 
Description PHE 
Organisation Public Health England
Country United Kingdom 
Sector Public 
PI Contribution Epidemiological expertise, data collection and analysis, dissemination
Collaborator Contribution Partnership in audit of perinatal HIV infections in the UK involving participation in expert panel assessing circumstances around new infant HIV infections in the UK.
Impact To date, an oral presentation at the 2014 Children's HIV Association Conference in Liverpool.
Start Year 2012
 
Description CHIVA 2014 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Health professionals
Results and Impact Oral presentation at a national conference of the Children's HIV Association.

Highlighted work being conducted by the National Screening Committee's Infectious Diseases in Pregnancy Screening Programme to explore how HIV screening policies could be improved.
Year(s) Of Engagement Activity 2014
 
Description IWHOD 2013 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Type Of Presentation Poster Presentation
Geographic Reach International
Primary Audience Other academic audiences (collaborators, peers etc.)
Results and Impact Presented a poster at this closed workshop.

L Byrne, C Thorne, P Tookey. Setting of diagnosis and CD4 count in the pregnancies of women diagnosed with HIV prior to conception, UK and Ireland 2007-2012. International Workshop on HIV Observational Databases, Cavtat, 11-13 April 2013

N/A
Year(s) Of Engagement Activity 2013
 
Description London HIV and Pregnancy Group 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Health professionals
Results and Impact Attendance at regular group meetings to share research findings, get in-put from practicing clinicians and to shape future research agenda

New avenues of research have been identified
Year(s) Of Engagement Activity 2013
 
Description World AIDS Day RCOG BHIVA 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact Presented a presentation "An audit of children with perinatal HIV born in the UK since 2006" at the event Prevention of Perinatal HIV Infection: Aiming for zero transmission. BHIVA multidisciplinary event marking World AIDS Day, Friday 27 November 2015, London, UK
Year(s) Of Engagement Activity 2015
URL http://www.bhiva.org/prevention-of-infant-HIV-infection.aspx