CHIPS Annual Report 2012/13
Collaborative HIV Paediatric Study (CHIPS)
Annual Report 2012/13
September 2013
Introduction
CHIPS is a multi-centre cohort study of HIV-infected children in the UK and Ireland. It was
established in 2000 and is a collaboration between clinics caring for HIV infected children, the
National Study of HIV in Pregnancy and Childhood (NSHPC) at the Institute of Child Health, and
the Medical Research Council (MRC) Clinical Trials Unit which also coordinates the Paediatric
European Network for the Treatment of AIDS (PENTA) trials.
The main objectives of CHIPS are 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 that standardised and high
quality paediatrician-led care can be delivered to all HIV-infected children in the UK and
Ireland.
CHIPS is primarily funded by the NHS London Specialised Commissioning Group.
How CHIPS works
Children born to HIV-infected women or those found to have HIV infection after birth are
initially reported to the NSHPC. The NSHPC then notifies CHIPS of any children with confirmed
infection, and for each of these children baseline and annual follow-up CHIPS forms are sent to
the main clinic of care for completion.
Summary data to the end of March 20131
A total of 1,835 children were reported to CHIPS by the end of March 2013, comprising virtually
all of those receiving HIV-related care in the UK and Ireland from 2006 onwards. In 2009, 77
children were newly reported to CHIPS, and similarly 57 in 2010 and 49 from 2011 onwards,
with the decline largely due to reporting delay of new cases to the NSHPC, as well as
ascertainment of infection status in infants born in the UK and Ireland. Of the 1,835, 109
children were known to have died whilst receiving paediatric care, including six deaths in 2008,
six in 2009, two in 2010 and one in 2011.
A further 467 young people left paediatric care and transitioned to adult clinics, with
approximately 50-100 transferring each year between 2007 and 2012, and for whom the
median age at transfer was 17.6 years. Thus the number of children in CHIPS is remaining
relatively stable overall as the annual number of new diagnoses roughly equates with numbers
dying and transferring to adult care.
Of the 1,835, 44% were born in the UK or Ireland, 54% were born abroad and 2% unknown.
For those born in the UK or Ireland, the median age at first presentation has been relatively
constant at around 6 months over the last two decades although 11% did not present until ≥5
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Numbers are based on reports received rather than children seen to the end of March 2013. 2012/13 data are
subject to reporting delay and may therefore be incomplete.
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CHIPS Annual Report 2012/13
years of age. For children born abroad, median age at presentation increased from less than 2
years before 1991 to around 6 years in 1997-2002 and 10 years in 2009 onwards. Similarly the
age distribution by year of follow-up of the cohort has changed considerably over the years. In
1996 the median age was 5.1 years (inter-quartile range, IQR 2.9-7.6) and this has increased
year on year to 13.3 years (IQR 10.1-15.5) in 2012/3. Similarly, the proportion of the cohort
aged ≥15 years increased from <1% in 1996 to 31% in 2013. The rate of hospital admissions in
the cohort has declined from 0.6 per child year in 2000 to 0.1 in 2011. Viral load suppression
among those starting combination ART naïve improved with calendar time: 59% suppressed
viral load ≤50c/ml at 12 months in 2001/3, increasing to 73% for 2010 onwards.
Of the 1,835 children reported to CHIPS, 1,131 were alive and in active follow-up at a CHIPS
clinic at the end of March 2013. Of these, just over half (52%) were female, 48% were born in
the UK or Ireland, 80% were of black African ethnicity, and nearly all (96%) were known to have
been infected through mother-to-child transmission. Fifty percent of children were being seen
at clinics in London, 39% in the rest of England, 4% in Scotland, 1% in Wales, 5% in the Republic
of Ireland, and <1% in Northern Ireland. A fifth (23%) had progressed to CDC stage B and
another 21% to CDC stage C during follow-up. At last follow-up, 12% remained ART naive, 5%
were on mono or dual therapy, 41% were on their initial combination antiretroviral regimen
while 36% were on their subsequent combination antiretroviral regimens. Six per cent were
off all antiretroviral drugs after having previously taken them.
Developments 2012/13
Follow-up into adult care:
 We continue to recruit into AALPHI (Adolescents and Adults Living with Perinatal HIV
cohort). This study has funding from the Monument Trust and will recruit 400 young
people with perinatal HIV in paediatric or adult care, and 300 HIV-uninfected but HIVaffected young people. Participants have a 2-hour annual interview with a research nurse.
To date, we have recruited 118 HIV infected and 25 affected adolescents. To assist in the
recruitment of affected young people, we have extended the upper age limit from 21 to 23
years and to include negative friends as well as siblings of positive young people. If you
have any ideas on how to increase recruitment numbers or how to attract parents and
young people to the study we are always keen for suggestions. Please contact our research
nurse, Kate Sturgeon, for more information (k.sturgeon@ucl.ac.uk).
 Young people attending clinics which are not participating in AALPHI are being invited to
join the UK Register of HIV Seroconverters. The UK Register is a national cohort of
individuals whose time of HIV seroconversion can be reliably estimated. We are
encouraging young people with perinatal infection to give consent to join the UK Register
(at age 16+), which will provide critical data on the long-term consequences of HIV and ART
in adulthood. In order to participate, young people need to agree to an annual review of
their HIV medical records, and no further visits or tests are required. The coordinator of
the UK Register is Louise Walker-Nthenda (Louise.Walker-Nthenda@ucl.ac.uk).
 We have written to all paediatric clinics participating in CHIPS about what they need to do
next in terms of recruitment into the UK Register and AALPHI. Please contact us
(mrcctu.chips@ucl.ac.uk) if we can advise you on next steps.
 We are now regularly matching CHIPS data on young people leaving paediatric care to the
Survey Of Prevalent HIV Infections Diagnosed (SOPHID), held at Public Health England,
which is an annual survey of all HIV-infected adults receiving treatment in the UK. This will
enable us to track young people who are not in the UK Register or AALPHI into adult care.
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CHIPS Annual Report 2012/13
SOPHID collects a restricted dataset, including most recent ART regimen, CD4 count and
viral load.
UK and Ireland:
 For 97% of children followed in CHIPS a follow up form was received for 2010-13.
 Slide sets containing annual feedback data were sent to all contributing clinics in May.
 We have been working with the London Specialised Commissioning Group and the
Perinatal, Paediatric and Young People (PePYP) HIV Subgroup to develop a set of paediatric
HIV outcome measures to assist commissioning of services. These have now been finalised
and are available from us on request.
 We are now collecting Soundex on the CHIPS forms, to facilitate flagging duplicate reports.
Soundex is an anonymised representation of a surname, and consists of the initial letter of
the surname followed by three digits (eg Chips = C120). No Soundex is unique to a single
name, and a name cannot be recreated from a Soundex code, so it is not possible to breach
confidentiality by providing it.
 We have further harmonised the data collected for CHIPS with the UK Register, to ensure
that analyses over the lifecourse of infection, and across paediatric and adult care, can be
conducted. This has included a review of the data collected on the CHIPS form, and some
amendments to the form have been made, including removing the questions on tanner
stage and introducing a question on pregnancy in young women in CHIPS.
 We have conducted an analysis of switch to second-line therapy. Of patients who
experienced virological failure, nearly a third (31%) switched to second-line therapy while
more than a third (38%) resuppressed without any ART changes. A further 11% remained
on a failing regimen without switching. We found that patients with lower CD4% and higher
viral load at virological failure changed their regimen faster, whilst those on boosted PIbased regimens were slower to switch than those on EFV-based regimens.
 We have conducted an analysis of virological response. Risk of virological failure during
follow-up after ART initiation was higher for 3-drug NVP-based first-line regimens
compared to 3-drug EFV-, 4-drug NNRTI-, and PI-based regimens. We also found
adolescents were less likely to maintain suppression, possibly due to poor adherence. An
EPPICC analysis is planned to investigate these findings further.
Europe:
 CHIPS is playing a key role in an exciting new global paediatric cohort collaboration called
CIPHER (http://www.iasociety.org/cipher.aspx), which is sponsored by the International
AIDS Society (IAS). This collaboration of regional cohort collaborations is taking forward
two global analyses of children with HIV, on adolescents and also duration of first-line
therapy, and CHIPS staff (Ali and Jeannie) are co-leading both projects.
 Within EuroCoord, the EU Network of Excellence consisting of the largest HIV cohorts and
cohort collaborations within Europe, CHIPS leads a new “Kids to Adults” work package,
whose aim is to strategically explore methods to ensure continued follow-up of patients as
they transfer from paediatric to adult care across Europe. The first project of this group is
an online survey of paediatric and adult cohorts in Europe to assess the degree to which
perinatally infected young people are being followed by cohort studies once they transfer
to adult care.
 CHIPS continues to take forward the paediatric component of the COHERE PLATO II project,
which investigated the incidence of triple class virological failure in children across the EU,
and factors associated with response. Following on from the first paper which was
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CHIPS Annual Report 2012/13
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published in the Lancet in 2011 (Lancet 2011;377:1580-1587), we have now presented
additional analyses directly comparing the rate of triple class failure in children and adults
at two conferences this year.
CHIPS also contributes data to the European Pregnancy and Paediatric HIV Cohort
Collaboration (EPPICC) pharmacovigilance programme, which this year was investigating
the long-term safety of abacavir, atazanavir and darunavir in children and adolescents.
Next year, we will also be looking at the safety of combivir, etravirine and tenofovir.
EPPICC recently published a paper investigating the use of combination neonatal
prophylaxis for the prevention of mother-to-child transmission of HIV in European high risk
infants (see below for full reference).
Staffing and UCL:
 CHIPS staff: We are saying goodbye to our statistician Caroline O’Leary who is leaving the
MRC CTU, and also Trinh Duong who is moving jobs within the CTU – we wish them both
well in their new posts. Recent additions to the CHIPS team are Tristan Childs (statistician),
Jeannie Collins (epidemiologist), Donna Dobson (data manager) and Anna Tostevin
(database coordinator).
 AALPHI staff: For those of you who knew our AALPHI research nurses who got the study up
and running, we are delighted to announce that Marthe Le Prevost had a baby boy at the
beginning of July, and we are very sad to say goodbye to Linda McDonald, who is moving to
Israel. We welcome our new research nurses, Kate Sturgeon, Susanna Stevens and Katie
Rowson.
 As of 1 August 2013 the MRC Clinical Trials Unit is now part of University College London,
but it still receives core funding from the MRC. This change has made little difference to
our working practices day to day, and we are still based at Aviation House on Kingsway.
Published papers and conference presentations
CHIPS data have been presented at the following national and international meetings in the
last 12 months:
 Shingadia D, Childs T, Duong T, Judd A, Collins IJ, Shackley F et al. Switch to second-line
antiretroviral therapy and evidence of re-suppression without treatment change after
virological failure in children in the UK/Ireland. 31th Annual of the European Society for
Paediatric Infectious Diseases, Milan, 2013 (poster presentation, abstract number A534-0018-01064
 Duong T, Judd A, Doerholt K, Lyall H, Menson E, Foster C et al. Long-term virological
outcomes in HIV-infected children on ART in UK/Ireland. 17th International Workshop
on HIV Observational Databases, Cavtat, 2013, and 7th IAS Conference on HIV
Pathogenesis, Treatment and Prevention, Kuala Lumpur, 2013 (oral presentation
MOAB0105).
 Wittkop L on behalf of the EuroCoord-CHAIN subtype project team. Effect of HIV-1
subtypes on virological and immunological response to initial combination antiretroviral
therapy (cART) – a European multicohort study. 20th Conference on Retroviruses and
Opportunistic Infections, Atlanta, 2013.
 Judd A et al. Sex, drugs and mental health: Characteristics of perinatally HIV-infected
young people recruited into the new Adolescents and Adults Living with Perinatal HIV
(AALPHI) cohort. 17th International Workshop on HIV Observational Databases, Cavtat,
2013, and 5th International Workshop on HIV Pediatrics, Kuala Lumpur, 2013.
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CHIPS Annual Report 2012/13
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Rojo Conejo P on behalf of the PLATO II project team of COHERE. Higher rates of triple
class virologic failure in perinatally HIV-infected teenagers compared to heterosexually
infected young adults in the PLATO II study. 17th International Workshop on HIV
Observational Databases, Cavtat, 2013, and 5th International Workshop on HIV
Pediatrics, Kuala Lumpur, 2013.
Turkova A. European cohort collaborations. 7th Annual Conference of the Children’s
HIV Association, Leeds, May 2013.
In addition, the following papers, based wholly or partly on CHIPS data, have been published in
or submitted to peer review journals:
 Judd A, Duong T, Galli L et al. Post-licensing safety of fosamprenavir in HIV-infected
children in Europe. Pharmacoepidemiology and Drug Safety – under review.
 Fish R, Judd A, Jungmann E, Foster C. Mortality amongst HIV-infected young people
following transition to adult care: an HIV Young Persons Network (HYPNet) audit. HIV
Medicine – in press.
 Pursuing Later Treatment Options II (PLATO II) project team; Collaboration of
Observational HIV Epidemiological Research Europe (COHERE) Group. Predictors of
CD4(+) T-cell counts of HIV type 1-infected persons after virologic failure of all 3 original
antiretroviral drug classes. J Infect Dis 2013; 207(5): 759-67.
 European Pregnancy and Paediatric HIV Cohort Collaboration (EPPICC) study group in
EuroCoord. Use of combination neonatal prophylaxis for the prevention of mother-tochild transmission of HIV infection in European high-risk infants. AIDS. 2013; 27(6) 9911000.
 Donegan K, Doerholt K, Judd A et al, on behalf of the Collaborative HIV Paediatric Study
(CHIPS). Lopinavir dosing in HIV-infected children in the UK and Ireland. PIDJ 2013; 32:
45-50.
 Kenny J, Musiime V, Judd A, Gibb D. Recent advances in pharmacovigilance of
antiretroviral therapy in HIV-infected and exposed children. Current Opinion in HIV AIDS
2012; 7(4): 305-16.
Please visit our website (www.chipscohort.ac.uk) to obtain further details of talks and papers
as well as downloads where available.
Work in progress and future plans
Over the coming months we plan to:
 continue to work with clinics to gain consent from those aged ≥16 years to join the UK
Register, and HIV-infected and affected young people to join AALPHI, to ensure
continued follow-up of the cohort into adult care
 further develop collaborations with SOPHID, as well as the UK CHIC study, with a view
to preparing a manuscript on the health outcomes of young people following transition
to adult care
 publish the analyses of switching to second line, and virological failure
 complete the write up of the PLATO II second paediatric analysis
 continue to support commissioning needs by producing and refining outcome measures
for paediatric care
 continue to lead analyses of data from Europe-wide and global individual patient metaanalyses, including on long-term pharmacovigilance.
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CHIPS Annual Report 2012/13
Forthcoming meetings
CHIVA runs a series of educational meetings, held bi-monthly in central London. For further
information please contact Navrup Kaur at the MRC Clinical Trials Unit
(mrcctu.hivchiva@ucl.ac.uk).
Contacts for further information
Please visit our website for further information about CHIPS: www.chipscohort.ac.uk
Alternatively, please contact the CHIPS Data Manager by email: mrcctu.chips@ucl.ac.uk.
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