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.
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.
Organisations
- University College London (Fellow, Lead Research Organisation)
- Victor Babes Hospital (Collaboration)
- Bicêtre Hospital (Collaboration)
- PUBLIC HEALTH ENGLAND (Collaboration)
- University of Padova (Collaboration)
- University of Florence (Collaboration)
- Swiss HIV Cohort Study (SHCS) (Collaboration)
- Medical Research Council (MRC) (Collaboration)
- National Institutes of Health (NIH) (Collaboration)
- Queen Mary University of London (Fellow)
Publications
Townsend C
(2013)
MTCT continues to decline in the UK and Ireland: 2007-2011
Byrne L.
(2013)
Place of diagnosis and CD4 count in pregnant HIV-positive women diagnosed before conception in the UK and Ireland (2007-2012)
in HIV MEDICINE
Samuel M
(2014)
Antenatal Atazanavir: A Retrospective Analysis of Pregnancies Exposed to Atazanavir
in Infectious Diseases in Obstetrics and Gynecology
Peters, H
(2014)
Variation in mode of delivery for HIV-positive women in UK and Irish hospitals, 2008-2013
in HIV Medicine
Byrne L
(2014)
Pregnancy outcomes in women growing up with perinatally acquired HIV in the United Kingdom and Ireland.
in Journal of the International AIDS Society
Townsend CL
(2014)
Earlier initiation of ART and further decline in mother-to-child HIV transmission rates, 2000-2011.
in AIDS (London, England)
Peters H
(2015)
Duration of ruptured membranes and mother-to-child HIV transmission: a prospective population-based surveillance study
in BJOG: An International Journal of Obstetrics & Gynaecology
French CE
(2017)
Presentation for care and antenatal management of HIV in the UK, 2009-2014.
in HIV medicine
Byrne L
(2017)
Pregnancy incidence and outcomes in women with perinatal HIV infection.
in AIDS (London, England)
Peters H
(2018)
National audit of perinatal HIV infections in the UK, 2006-2013: what lessons can be learnt?
in HIV medicine
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 | 03/2015 |
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 | 06/2015 |
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 | 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 | 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 |