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					                                            NSHPC update, January 2009

                        Obstetric and paediatric HIV
                             surveillance data from
                                  the UK and Ireland
        NSHPC
                                          National Study of HIV in
                                        Pregnancy and Childhood

   Further information nshpc@ich.ucl.ac.uk Principal Investigator Pat Tookey

The NSHPC is a collaboration between the Centre for Paediatric Epidemiology
  and Biostatistics, UCL Institute of Child Health, the Health Protection Agency
                          Centre for Infections, and Health Protection Scotland
10827 pregnancies
reported through RCOG by December 2008
  632 continuing to term                                   6%
  8677 deliveries                                         80%
     8566 live births, 111 stillbirths
  679 terminations                                         6%
  525 spontaneous abortions                                5%
  314 other outcomes                                       3%
       3 maternal deaths in pregnancy
       30 ectopic pregnancies
       146 went abroad before delivery
       135 outcome not known

                                          NSHPC / UCL ICH / January 2009
Children born to HIV infected women
reported to NSHPC 1986- December 2008
 11495 children (of whom ~8% born abroad)
      49% reported from London
      36% from rest of England
      4% from Scotland
      1% from Wales and Northern Ireland
      10% from Ireland
 70% not infected
 15% indeterminate
    majority (~98%) likely to be uninfected
 15% infected
                                 NSHPC / UCL ICH / January 2009
How children acquired infection
2145 paediatric infections reported to NSHPC
1986 – December 2008
   Mother-to-child transmission                 1751
   Blood factor treatment                        267
   Blood/tissue transfer                          58
   Other/undetermined                             69

 About 16% of all infected children ever reported in the
  UK and Ireland are known to have died
 About 11% have left the country or are otherwise lost to
  follow up
                                   NSHPC / UCL ICH / January 2009
                 HIV prevalence1 among pregnant women by area of
                 residence (adapted from Testing Times, HPA 2007, Fig 3.3.1)
                     0.6%          Inner London
                                   Outer London
                     0.5%          Rest of England
                                   Scotland
    HIV prevalence




                     0.4%


                     0.3%


                     0.2%


                     0.1%


                     0.0%
                            1994      1996     1998   2000      2002         2004      2006

1Unlinkedanonymous survey of newborn infant dried blood spots, NSHPC   / UCL ICH / January 2009
England & Scotland. Includes diagnosed and undiagnosed women.
Mother-to-child transmission of HIV
 In the UK, if an HIV infected pregnant woman is
  unaware of her infection status, her baby has a
  roughly 1 in 4 chance of being infected
 Effective interventions substantially reduce the
  risk of mother-to-child transmission of infection,
  but can only be offered to pregnant women who
  are aware of their HIV infection
 Using antiretroviral therapy (ART) antenatally,
  during delivery and for the infant, delivery by
  elective caesarean section, and avoiding breast
  feeding can reduce rates of mother-to-child
  transmission to around 1%

                                NSHPC / UCL ICH / January 2009
    Low rates of mother-to-child transmission
    (MTCT) of HIV in the UK and Ireland, 2000-2006
 5151 diagnosed women with known infection status for infants
         Overall MTCT rate 1.2% (95% CI: 0.9-1.5%, 61/5151)
         1.6% in 2000-02 and 1.0% in 2003-06
         0.8% in women who received at least 14 days of ART (40/4864)

 No transmissions among 464 women on zidovudine monotherapy
  delivering by planned caesarean section
 Among women on HAART
         MTCT rate 0.7% among 2286 women who had planned caesarean sections
         MTCT rate 0.7% among 559 women who had planned vaginal deliveries
         Only 3 transmissions (0.1%) among 2117 women with viral load <50
          copies/ml - two babies with evidence of in utero transmission
                                                    Townsend et al. AIDS 2008; 22:973-81

    See also poster on MTCT rates available on NSHPC website:
     http://www.nshpc.ucl.ac.uk/slides/NSHPC_poster_CROI_2008_pdf.pdf


                                                 NSHPC / UCL ICH / January 2009
Maternal diagnosis prior to delivery
and mother-to-child transmission
 The proportion of all exposed infants (born to
  diagnosed and undiagnosed infected women in
  the UK) who are infected has declined from an
  estimated 9% in 2000 to about 3% since 2005
 The actual number of infected infants born in the
  UK each year has probably remained fairly
  constant since 2000 because of the increasing
  prevalence of infection among women
                       see “Testing Times” HPA 2007

                               NSHPC / UCL ICH / January 2009
 Antenatal testing and diagnosis rates
 data for England
 In the mid 1990s ~30% of infected pregnant women were
  diagnosed before delivery, rising to ~60% by 1999
 Routine offer and recommendation antenatal policy
  implemented in almost all English units by end 2001, and
  throughout UK by end 2003
 Uptake of testing >80% in about 2/3 of units in 2003, but
  only reached 90% target in about 1/3; 20% of units still
  had no robust method to estimate uptake
 ~ 70% of infected pregnant women diagnosed by delivery
  in 2000, 80% 2001/2, 90% 2003/4, and ~ 95% since 2005
                 NSHPC and unlinked anonymous survey data
                 Townsend et al. Uptake of antenatal HIV testing in the UK:
                  2000-2003. J Public Health 2006; 28: p. 248-52

                                           NSHPC / UCL ICH / January 2009
Timing of maternal HIV diagnosis
UK/Ireland pregnancies (all outcomes), reported to NSHPC by Dec 2008
  number
 900
 800          before this pregnancy
 700          during this pregnancy
 600
 500
 400
 300
 200
 100
   0
       1994    1996    1998   2000     2002    2004     2006    2008*
                                year of EDD               *incomplete
                                         NSHPC / UCL ICH / January 2009
Antiretroviral therapy in pregnancy

 In the UK and Ireland, about 50% of previously
  diagnosed women are on ART at conception (~20%
  of all women diagnosed before delivery)
 Most previously untreated / undiagnosed women start
  ART in pregnancy, usually between 23 and 30 weeks
 About 98% of diagnosed pregnant women take ART
    wide variety of drug combinations and timing of treatment

 Beneficial effects of ART in reducing mother-to-child
  transmission are clear


                                      NSHPC / UCL ICH / January 2009
Antiretroviral therapy and congenital abnormalities,
infants born in the UK and Ireland, 1990-2003
 Overall congenital abnormality rate – 3.2% (101/3172)
    Consistent with 2-3% reported for major birth defects in England
 No evidence of a significant association between
  exposure to ART and prevalence of abnormalities
    3.4% in 2657 pregnancies with ART exposure, 2.2% in 463
     pregnancies without (OR 1.6, 95% CI 0.8-3.1, p=0.17)
    No significant difference according to timing or type of ART
 Findings consistent with international Antiretroviral
  Pregnancy Registry, and other European studies
 Insufficient numbers to explore individual drug
  combinations, or subgroups of abnormalities
                       Townsend et al. JAIDS 2006; 42(1): 91-94

                                         NSHPC / UCL ICH / January 2009
ART and premature delivery,
diagnosed HIV infected women in UK
and Ireland, 1990-2005
 Premature delivery rate (<37wks) 1.5 times higher in women on
  HAART vs. mono/dual therapy
 Stronger effect at earlier gestational ages
         <37 wks             AOR=1.5 (1.2-1.9, p=0.001)
         <35 wks             AOR=2.3 (1.6-3.4, p<0.001)
         <32 wks             AOR=2.7 (1.5-4.9, p=0.001)
 AOR=odds ratio adjusted for HIV symptoms / AIDS, injecting drug
  use, ethnic origin & maternal age
                                                 Townsend at al. AIDS 2007; 21:1019-26

   See also poster on prematurity and ART available on NSHPC website:
    http://www.nshpc.ucl.ac.uk/slides/NSHPC_poster_AIDS_2006.pdf


                                                 NSHPC / UCL ICH / January 2009
Infection status of children born
to HIV infected women
 All children born to HIV infected women and reported to
  NSHPC are followed up to establish infection status
 Classification of infection status depends on reports of
  test results
    Most children currently described as ‘indeterminate’ and born in
     recent years will be uninfected, but final test results have not
     yet been received; those from earlier years are generally lost to
     follow up or left the country before infection status was clarified
 Mother-to-child transmission rates cannot be directly
  derived from surveillance reports as there is a bias
  towards diagnosis and reporting of infected children

                                          NSHPC / UCL ICH / January 2009
  Children born in the UK or Ireland, to women
  diagnosed before delivery, infection status reported to
  NSHPC by December 2008
1400            infected
1200            indeterminate
1000            not infected
800
600
400
200
  0
        pre 1990-   1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007* 2008*
       1990 1996

                                   year of birth              * incomplete
                                               NSHPC / UCL ICH / January 2009
  Children born in the UK or Ireland, to women
  diagnosed before delivery
  likely infection status
1400
                    infected
1200
1000                not infected

800
600
400
200
  0
        pre 1990-      1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007* 2008*
       1990 1996

                                      year of birth              * incomplete
                                                  NSHPC / UCL ICH / January 2009
 Children born since 1996 in the UK,
 to women who were diagnosed before delivery,
 infection status reported to NSHPC by December 2008
1200
              infected
1000
              indeterminate
800
              not infected
600

400

200

  0
       1996    1997   1998   1999   2000   2001   2002   2003   2004   2005   2006   2007* 2008*

                                           year of birth                         * incomplete
                                                          NSHPC / UCL ICH / January 2009
 Children born since 1996 in the UK,
 to women who were diagnosed before delivery,
 likely infection status
1200

1000          infected

 800
              not infected
 600

 400

 200

   0
       1996    1997   1998   1999   2000   2001   2002   2003   2004   2005   2006    2007*   2008*

                                            year of birth                            * incomplete
                                                          NSHPC / UCL ICH / January 2009
 Children born since 1996 in Ireland,
 to women who were diagnosed before delivery,
 infection status reported to NSHPC by December 2008
160
         infected
120      indeterminate
         not infected
80


40


 0
      1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007* 2008*

                                year of birth                  * incomplete
                                            NSHPC / UCL ICH / January 2009
 Children born since 1996 in Ireland,
 to women who were diagnosed before delivery,
  likely infection status
160

          infected
120
          not infected
80


40


 0
      1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007* 2008*

                                year of birth                  * incomplete
                                            NSHPC / UCL ICH / January 2009
NSHPC paediatric follow-up protocol
 Annual follow-up information is sought for
  all infected children
   through CHIPS (Collaborative HIV Paediatric
    Study)
 Annual follow-up of uninfected children born
  to infected women in the UK
   was carried out through the CHART (Children
    exposed to Antiretroviral Therapy) study, 2002-
    2005
   less intensive alternative methods of follow up are
    currently being developed
                                 NSHPC / UCL ICH / January 2009
Collaborative HIV Paediatric Study
 Collaboration since 2000 between the NSHPC,
  the MRC Clinical Trials Unit and the centres
  looking after infected children
 Collects more detailed clinical, laboratory and
  treatment information than is possible through
  routine surveillance
          Includes >95% of HIV infected children
           reported to the NSHPC, intention to
           include all infected children


                             NSHPC / UCL ICH / January 2009
Outcomes in perinatally infected children
                                        (UK and Ireland)
 Increasing proportion of infected children on ART
 Mortality rates declined by 80%, progression to AIDS by
  50% between 1997 and 2001/2 (and sustained since)
 Hospital admission rates declined by 80%, but number
  of hospital admissions by 25% only (due to increasing
  number of infected children)
 Improvements more marked for children than infants
          Improvements in survival for infants, but not in
           rates of disease progression
                            Gibb et al, BMJ 2003; 327;1019
                            Doerholt et al, PIDJ. 2006; 25(5):420-6
                            Judd et al, CID. 2007;45(7):918-24
                                    NSHPC / UCL ICH / January 2009
 Perinatal Transmission of HIV in
 England 2002-2005 (Audit)
 This audit was carried out as a collaboration between
  the NSHPC, the Audit Information & Analysis Unit for
  Specialised Services, London HIV Consortium and
  CHIVA
 87 cases were confirmed and eligible for the audit by
  end 2005
 Infants born in all parts of England, about 1/3 to
  diagnosed women, 2/3 to undiagnosed women
 Routinely collected surveillance data available for all
 Clinicians provided additional data for 93% of cases

                                    NSHPC / UCL ICH / January 2009
Summary findings: contributory factors / outcome
 Antenatal testing not offered, or declined in some cases
 Delay in antenatal testing, or reporting of results
 Seroconversion in pregnancy (minimum estimate 15%)
 Concurrent infections or conditions
 Delay in initiating or changing treatment
 Late diagnosis and/or premature delivery
 Communication failure within Trusts / after transfer of care
 Adverse social circumstances in many families
 Among 33 infants born to diagnosed women 2 have died to
  date, and 20% of survivors had AIDS defining illness
 Among 54 born to undiagnosed women 9 have died to
  date, and 60% of survivors had AIDS defining illness
                                    NSHPC / UCL ICH / January 2009
Perinatal Transmission of HIV in
England 2002-2005
Executive Summary and Recommendations, and
powerpoint slide presentation of findings available
on the NSHPC website
           www.nshpc.ucl.ac.uk/
Executive Summary and Recommendations also
available at
             www.chiva.org.uk/
NHS network access at nww.esussexaiau.nhs.uk/

                               NSHPC / UCL ICH / January 2009
Follow up of uninfected children
exposed to ART (CHART study)
 Set up to investigate logistics of long-term follow up of
  these children, and to explore whether any serious
  adverse outcomes associated with exposure to ART in
  fetal and/or early life were apparent in early childhood
 Enrolled uninfected children born in the UK and reported
  to NSHPC; study conducted 2002-2005
 Prospective data on ART exposure and perinatal details
  routinely collected through NSHPC
 CHART data on health/development in early childhood
 Survey of parents & professionals’ views about follow up

                                   NSHPC / UCL ICH / January 2009
 Findings from CHART –
 Survey of parents & professionals’ views
 140 parents of uninfected children
 40 health professionals approached for CHART
 Four possible follow up options outlined: clinic, postal, or
  telephone follow up, or data linkage (no direct contact)
 99% found at least one strategy acceptable
 Least preferred options were postal follow up (parents),
  and clinic follow up (professionals)
 No single preferred option emerged
 ¾ of parents wanted any direct contact to be through
  them, even when child grown up
              Hankin et al. AIDS Care 2007; 19(4):482-86
                                     NSHPC / UCL ICH / January 2009
 Findings from CHART –
 Flagging for death and cancer
 Flagging – data linkage between study data and
  ONS data on death and cancer registrations

 95% of children born 2001-2004 and reported to
  NSHPC were flagged
   Confidentiality (no names, matching algorithm)
   Prospectively collected data on ART exposure etc
   Will be able to monitor death and cancer over time

                  Hankin et al, AIDS 2007, 21:867-87
                                  NSHPC / UCL ICH / January 2009
  Recent publications            for full list see www.nshpc.ucl.ac.uk
• Townsend et al. Trends in management and outcome of pregnancies in
  HIV infected women in the United Kingdom and Ireland, 1990-2006.
  BJOG 2008; 115:1078-86
• Chakraborty R et al, on behalf of CHIPS and UK Collaborative Group
  on HIV Drug Resistance. HIV-1 drug resistance in HIV-1 infected
  children in the UK from 1998 to 2004. PIDJ 2008;27(5):457-59
• Townsend et al. Low rates of mother-to-child transmission of HIV
  following effective pregnancy interventions in the United Kingdom and
  Ireland, 2000-2006. AIDS 2008; 22:973-81
• Thorne et al (NSHPC and ECS). Pregnancies in young women with
  vertically-acquired HIV infection in Europe. AIDS 2007, 21:2552-56
 Judd et al. (CHIPS and NSHPC). Morbidity, mortality, and response to
  treatment by children in the UK and Ireland with perinatally acquired
  HIV infection during 1996-2006: planning for teenage and adult care.
  CID 2007 Oct 1;45(7):918-24
 Townsend et al. ART and premature delivery in diagnosed HIV-infected
  women in the UK and Ireland. AIDS 2007; 21:1019-26

                                         NSHPC / UCL ICH / January 2009
Public health surveillance role of NSHPC, and basis
for epidemiological and clinical research / audit
 Map changing patterns/extent of HIV infection in pregnant
  women and children (geographical, demographic, clinical)
 Contribute to HPA & HPS surveillance of HIV in UK
 Provide timely data for service planning and resource
  allocation (SOPHID, specific regional data requests) to
  national, regional and local stakeholders, including patient
  and advocacy groups
 Role in assessing impact of antenatal screening
  programmes and uptake of interventions to prevent
  mother to child transmission
 Contribute aggregated data to Antenatal Pregnancy
  Registry, http://www.apregistry.com/

                                    NSHPC / UCL ICH / January 2009
    Ethics
   NSHPC, CHART, ONS flagging study originally by LREC
   NSHPC, CHIPS, CHART follow-up, CHART survey MREC 2004
   Audit study (2006) amendment to NSHPC protocol MREC 2006
   PIAG approval for collaboration with HPA for communicable disease
    surveillance (NSHPC specified), ONS flagging (current flagging
    studies 2002), BPSU HIV surveillance (current BPSU studies 2005)

    Funding
 The NSHPC was originally funded mainly by AVERT, then by the
  Department of Health. It now receives core funding from the HPA.
 The CHART study, and flagging costs, were funded by the Medical
  Research Council
 Claire Townsend is funded by an MRC Training Fellowship

     – Any views expressed in NSHPC publications / presentations are those of the
       authors, and not necessarily those of the funders
                                                   NSHPC / UCL ICH / January 2009
  Acknowledgements
 Royal College of Obstetricians & Gynaecologists and respondents
 British Paediatric Surveillance Unit (RCPCH) and respondents
 Everyone contributing to the Collaborative HIV Paediatric Study
  (CHIPS) at the MRC Clinical Trials Unit and the clinical centres
 Paediatric and family HIV clinic teams, staff and families
 Everyone contributing data to Antenatal Testing Uptake Survey
 The AIAU and everyone contributing to the Perinatal Infection Audit
 Health Protection Agency Centre for Infections, Health Protection
  Scotland, especially colleagues involved in HIV and STI surveillance
 Office for National Statistics
ICH team: Co-ordinator: Janet Masters
Researchers: Claire Townsend, Hiwot Haile-Selassie
Administrative Assistant: Icina Shakes
Additional support: Catherine Peckham, Mario Cortina-Borja
Principal Investigator: Pat Tookey
                                              Further information at
  NSHPC
    nshpc@ich.ucl.ac.uk                   NSHPC / UCL ICH / January 2009

				
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