CAB 34 – DHICE Community Training Day 18 June 2010

National Study of HIV in Pregnancy and Childhood

and

Collaborative HIV Paediatric Study

Pat Tookey, UCL Institute of Child Health

•  Who we are •  What we do •  Current picture •  Current work •  Ethics and governance •  CHIPS

Who we are

  Based at UCL Institute of Child Health in the MRC Centre of Epidemiology for Child Health

  Originally established in 1986 with core funding from AVERT (AIDS Education and Research Trust) and the Department of Health. Current contract with and core funding from the Health Protection Agency

  Specific research projects funded or supported by departmental or other sources

  Core team of three (Data Manager/Coordinator, Researcher, Administrative Assistant) with support from MRC Centre colleagues

What we do   National surveillance of, and research on, obstetric and

paediatric HIV (UK and Ireland)   Two reporting schemes run in collaboration with

  the Royal College of Obstetricians and Gynaecologists (RCOG) since 1989

  the Royal College of Paediatrics and Child Health’s British Paediatric Surveillance Unit (BPSU) since 1986

  Comprehensive reporting of   all pregnant women known to have HIV infection in pregnancy in

the UK or Ireland (diagnosed women)   all infants born to diagnosed women (exposed infants)   all children diagnosed in the UK or Ireland with HIV infection

(infected children), regardless of country of birth

Full details and summary data www.nshpc.ucl.ac.uk

What we do   No enrolment, no interventions, no direct contact

with patients, no patient names or addresses   NSHPC links mothers and babies by date, place

and other details   Information collected on demographics, timing of

women’s diagnosis, treatment and outcome of pregnancy, infection status of infants, and diagnosis in children

  Regular standard surveillance datasets to HPA to combine with adult HIV surveillance data www.hpa.org.uk

Children born to HIV infected women   All children born to HIV infected women are

followed up to establish infection status   Follow up information on treatment and health of

infected children collected every year (CHIPS)   Uninfected children

  Early information available for first year of life   Minimal follow up at present   Detailed follow up not possible (too many children)   Flagging with ONS for death / cancer reports

HPA / HPS SOPHID

CDR / HPS Weekly Quarterly tables Annual reports

Uninfected children CHART

(enrolment closed)

DH / CHINN / CHIVA Commissioners,

clinicians, local and regional requests

Infected children CHIPS

NSHPC, MRC CTU, paediatric centres, transition clinics NSHPC

analyses and publications

Children born E&W ONS

Flagging for death and cancer

Provide data for WHO / APR

Other collaborations as appropriate

Antenatal HIV screening:

surveys, programme development

and evaluation

ECS Inter/national

collaborations …. Pharmacovigilance data provision

Perinatal HIV – 20 years of surveillance

  Changing epidemiology of HIV   Advances in treatment and prevention   Success of routine antenatal testing   Survival of infected infants into adult life

  Challenges:   maintaining high uptake of antenatal testing   improving pregnancy care and further reducing MTCT rates   long term management/ follow up of perinatally infected children   transition from paediatric to adult care   monitoring exposed uninfected children in long term

Current Picture   Pregnant women and children in the UK and

Ireland   Most recent NSHPC data available on website

www.nshpc.ucl.ac.uk

HIV prevalence1 among pregnant women by area of residence (diagnosed and undiagnosed women)

1Unlinked anonymous survey of newborn infant dried blood spots, England & Scotland.

Impact of current protocol •  Antenatal HIV test recommended to all women since 2000 •  Uptake of testing exceeds 90% in most regions •  Overall detection rate exceeds 90% nationally •  60% of diagnosed women aware before current pregnancy •  Antenatal detection rate exceeds 80% nationally

•  Almost all diagnosed women accept interventions •  MTCT rate from diagnosed women 1.2% (CI 0.9-1.5%) •  Probable 25% transmission rate from undiagnosed women

(could be higher following seroconversion) •  Most UK-born infected infants have undiagnosed mothers

HIV infected pregnant women   Over 12,000 pregnancies reported in UK/Ireland

  over 90% since 2000   About three-quarters of women were born in sub-

Saharan Africa, 1 in 8 in UK or Ireland, 1 in 10 born elsewhere

  Currently   About 10% of women have HIV symptoms in pregnancy   Over half are diagnosed before current pregnancy   Over half of English reports are from outside London

Timing of maternal HIV diagnosis UK/Ireland: all births/pregnancies reported by March 2010

*incomplete

Trends over time, diagnosed women (Townsend et al, BJOG 2008)

1990-93 1994-96 1997-99 2000-03 2004-06 N. pregnancies (per year)

376 (94)

325 (108)

576 (192)

2941 (735)

4009 (1336)

% TOP 30% 15% 12% 5% 3%

Region SWNI London Rest England

Ireland

24% 51% 17% 8%

15% 65% 16% 4%

5% 76% 13% 6%

3% 57% 27% 13%

4% 45% 43% 8%

Women IDU UK/Irish born SSA born =>35 yrs Symptoms

49% 49% 43% 4%

22%

29% 33% 58% 6%

25%

16% 25% 67% 16% 19%

6% 15% 77% 17% 11%

3% 13% 79% 20% 11%

Low rates of MTCT of HIV in the UK and Ireland, 2000-2006 Townsend et al. AIDS 2008;22:973-81

•  Overall MTCT 1.2% (95% CI: 0.9-1.5%, 61/5151) –  0.8% in women with 14+ days of ART (40/4864)

•  464 women on ZDV mono with planned CS –  No transmissions

•  Minimal transmission from women on HAART delivering as planned –  MTCT rate 0.7% (2286 women with planned CS) –  MTCT rate 0.7% (559 women with planned VD) –  Only 3 transmissions (0.1%) in 2117 women with VL<50

(2 infants with evidence of in utero transmission

Current work

Current work   Usually through PhDs and Fellowships, eg   Sequential pregnancies   Pregnancies in African born women   Pregnancies in perintally infected women   Use of non-AZT ART in pregnancy   Vaginal delivery and ruptured membranes   New diagnoses in children

Why is MTCT still occurring? •  2007/8 audit of perinatal transmissions occurring in

England 2002-05 (NSHPC, AIAU, CHIVA) •  33 infants born to diagnosed women •  54 infants to women not diagnosed before delivery •  Audit identified a number of factors which might have

contributed to transmissions occurring •  Executive Summary and Recommendations at

www.nshpc.ucl.ac.uk/ and www.chiva.org.uk/

•  Over 40 more perinatally children identified since then, born in that period, most to undiagnosed women

Timing of maternal infection

•  Infected children whose mothers were not diagnosed before delivery have mothers who either –  had long-standing infection but declined, or were not

offered, antenatal testing, or –  tested negative at antenatal testing and seroconverted

during pregnancy, or –  tested negative at antenatal testing, and seroconverted

while breastfeeding •  some time between delivery and infant diagnosis

Perinatal infection – where now? •  Further data on circumstances surrounding MTCT to

infants born to diagnosed women •  Develop mechanisms for feedback to antenatal units

where undiagnosed women were delivered, and seek information on antenatal test offer in those cases

•  Establish contribution of postnatal seroconversions to perinatally acquired infection

•  Collect additional information on infected infants born to undiagnosed women (extending audit)

•  If evidence available, identify likely timing of maternal seroconversion and paediatric infection

•  Needs adequate support and extension to ethics

Ethics and governance   Research Ethics Committee   National Information Governance Board

  previously Patient Information Advisory Group   Institutional review   Steering Group   Peer review for publications   Feedback to interested groups

  Public websites   Talks and presentations

Ethics and governance

  Central London Research Ethics Committee   Ref MREC/04/2/009 (NSHPC)   Ref MREC/04/2/010 (CHIPS)   Annual reports to REC

  Any ‘Substantial Amendments’ to protocols have to be submitted for further review   eg, Audit of perinatal HIV infections in England 2002-2005

Ethics and governance   National Information Governance Board

  previously Patient Information Advisory Group   Established under Health & Social Care Act 2008, relating

to section 251 of the NHS Act 2006 which allows the common law duty of confidentiality to be set aside in specific circumstances

  NIGB’s Ethics and Confidentiality Committee reviews applications relating to collection of identifiable data without individual patient consent   Identifiable in this context means date of birth, NHS or clinic

number, postcode etc – rarely names or addresses   Applicants have to provide compelling reasons why

consent is not sought, and make annual progress reports to NIGB http://www.nigb.nhs.uk/

Ethics and governance   Institutional review

  ICH and HPA   Data protection   Institutional security policies

Ethics and governance   Steering Group, meets twice a year

  Terms of reference •  To ensure effective collection, use and dissemination of data, to

develop the research potential of the study, provide different perspectives on the study, provide specialist advice and support

  Collaborating institutions (HPA, HPS, ICH)   Clinical representatives   Lay representatives

  Positively Women   African HIV Policy Network

http://www.nshpc.ucl.ac.uk/

Ethics and governance   Peer review for publications   Feedback to interested groups

  Public websites   http://www.nshpc.ucl.ac.uk/   http://www.chipscohort.ac.uk/   http://www.chiva.org.uk/   http://bpsu.inopsu.com/studies/hiv/index.html

  Talks, presentations, reports   National and international HIV conferences   Clinical audiences, study days, research forums, interest groups   Public health and policy groups   Community settings eg Body & Soul,

Positively Women

www.chipscohort.ac.uk   Collaborative HIV Paediatric Study established in

April 2000 as a multi-centre cohort study of HIV-1 infected children in the UK and Ireland

  The collaboration is between –  70 clinics in the UK and Ireland

caring for HIV-infected children –  The National Study of HIV in

Pregnancy and Childhood (NSHPC), and

–  The MRC Clinical Trials Unit, where CHIPS is located

CHIPS Objectives   To describe clinical, laboratory and treatment data for

these children, and   To describe the use of paediatric HIV services   CHIPS aims to enhance the exchange of information and

expertise between clinics in order to promote standardised high quality paediatrician-led care of all HIV-infected children in the UK and Ireland

  CHIPS is primarily funded by   the London HIV Consortium, and has received

additional support from Bristol-Myers Squibb, Boehringer Ingelheim, GlaxoSmithKline, Roche, Abbott and Gilead

How CHIPS works   NSHPC provides initial data to CHIPS on all children with

confirmed HIV infection (date and place of birth, management in pregnancy if mother was diagnosed, perinatal details, confirmatory test results)

  For each child CHIPS sends a baseline and prospective CHIPS questionnaire to the clinic of care

  Follow up data then sought annually   Current health and growth   Treatment details, including reasons for change   Clinical results (viral load, CD4s etc)   Hospital admissions

MRC CTU

CHIPS

NSHPC

Participating centres

initial data on all infected children in participating centres

CHIPS data requested and supplied

summary annual data sent from CHIPS to NSHPC

Children seen elsewhere

NSHPC seeks summary annual data

Number of children followed up, and summary findings from 2009/10 Annual Report   1,645 children reported to CHIPS by end of March 2010

  91% of infected children reported to NSHPC since 1996, and virtually all those in HIV-related care from 2006 onwards

  206 had transferred to adult care (plans for follow up)   1,245 alive and in active follow-up at a CHIPS clinic

  48% born in UK or Ireland   79% of black African ethnicity   97% infected through mother-to-child transmission   25% had progressed to CDC stage B and another 25% to CDC

stage C during follow up   1 in 8 remained ART naïve, and   About 70% were on HAART   About 1 in 10 were off all ART after previously taking it

697 (56%) London

46 (4%) Scotland

422 (34%) Rest of England

59 (5%) Ireland

16 (1%) Wales

Regional distribution of main follow-up clinic for 1245 children alive and followed up in CHIPS

Children who have died, lost to follow-up, left the UK & Ireland or transferred to adult care are excluded

5 (0%) N. Ireland

N 357 413 491 555 649 748 848 973 1070 1144 1208 1251 1232 1098

Age distribution* of children in follow-up by year, 1996-2009

* Age is taken to be age at start of the year, or age at presentation if child presented during that year

Publications and reports / Networks   Numerous clinical and epidemiological papers, and

conference presentations   Wide dissemination of data through clinical networks

http://www.chipscohort.ac.uk/default.asp

  Plans for follow up into adult life   AALPHI – Adolescents and Adults Living with Perinatally acquired

HIV Infection (funding just secured for consented follow up study)

  Involvement in HYPNet, working on transition from paediatric to adult care http://www.hypnet.org.uk/index.html

Acknowledgments   Respondents to NSHPC and CHIPS   NSHPC and CHIPS teams and steering groups   Royal College of Obstetricians and

Gynaecologists   British Paediatric Surveillance Unit

  NSHPC funding The NSHPC receives core funding from the Health Protection Agency

Any views expressed are those of the speaker/author and not necessarily those of the HPA