CONCLUSIONS

1
Older and wiser continued improvements in
clinical outcome and highly active antiretroviral
therapy (HAART) response in HIV-infected children
in the UK and Ireland, 1996-2005
A Judd1, T Duong1, K Lee1, AS Walker1, PA
Tookey2, M Sharland3, A Riordan4, H Lyall5, J
Masters2, E Menson3, G Tudor-Williams5, K
Butler6, S Donaghy3, V Novelli7, C Peckham2, DM
Gibb1 for the Collaborative HIV Paediatric Study
and the National Study of HIV in Pregnancy and
Childhood
1 MRC CTU, London 2 Institute of Child Health,
London 3 St Georges Hospital, London 4 Royal
Liverpool Childrens Hospital, Liverpool 5 St
Marys Hospital, London 6 Our Ladys Hospital
for Sick Children, Dublin 7 Great Ormond Street
Hospital, London.
BACKGROUND The National Study of HIV in Pregnancy
and Childhood (NSHPC) is a voluntary
confidentialreporting scheme for HIV/AIDS
diagnoses in pregnant women and children,
covering the whole of the UK and Ireland. The
Collaborative HIV Paediatric Study (CHIPS) is a
multicentre cohort study of HIV infected children
under care in the UK and Ireland since 1996. 39
hospitals in the UK and Ireland currently
collaborate in the CHIPS study, accounting for
?90 of all children currently in the NSHPC.
CHIPS is being extended to the whole of the UK
and Ireland during 2006/7.

• METHODS
• Analyses relating to HAART exposure and response
  are confined to children in CHIPS only (n1065).
  All other analyses include all diagnosed children
  (n1439)
• Our definition of first line" 3 or 4 drug HAART
  allows for 1 or 2 drug substitutions (if not made
  for virological, immunological or clinical
  failure), and drug intensifications or reductions
• Logistic regression was used to explore responses
  to HAART. All odds ratios (ORs) are adjusted
  for age, CD4 and HIV-1 RNA at HAART initiation
  sex CDC B/C events prior to HAART number of
  drugs in the initial HAART regimen year started
  HAART and timing of response measurements

• HOW THE NSHPC CHIPS WORK TOGETHER
• Children diagnosed with HIV are initially
  reported to the NSHPC. Once the infection is
  confirmed, the NSHPC informs CHIPS, which sends
  out detailed annual followup questionnaires if
  the child is seen in a hospital collaborating in
  CHIPS. For hospitals not in CHIPS, abrief
  annual follow up form is sent out by the NSHPC.
  Data are shared between the studies in order
  toundertake joint analyses.
• AIM
• The aim of this analysis was to describe changes
  overtime in demographics, morbidity and
  mortality, and exposure and response to HAART, in
  HIV infectedchildren in the UK and Ireland
  between 1996 and 2005.

• SOCIODEMOGRAPHICS
• 50 female
• 72 black African, 13 white, 16 other
• 55 born in the UK and Ireland, 45 born abroad
• Median age at presentation varied by country of
  birth
• - constant for the UK and Ireland at 0.5 years
• - increased from 2 years up to 1991 to 8 years
  in 2004/5 for those born abroad
• 13 identified prospectively from birth, 68
  prior to an AIDS diagnosis, and 19 at AIDS
  diagnosis
• 94 vertically infected, 3 blood transfusion, 3
  other

• 12 MONTH IMMUNOLOGICAL AND VIROLOGICAL RESPONSE
  TO HAART
• 76 suppressed viral load lt400 copies/ml in
  2003/5, compared to only 51 in 1997/9.
• A cut off of lt50 copies/ml could not be used due
  to some hospitals continuing to use the lt400
  cut off in recent years. Multivariable.
  Baseline1997/9

• HAART EXPOSURE AND SWITCHING
• 595 children in CHIPS started a HAART
  regimensince 1997 and were ART naïve at the
  start of HAART
• 93 remained on first line HAART at 12
  months,86 at 24 months, and 79 at 36 months
• Median time to switching to second line was7.2
  years
• Whilst the proportion of child time spent on
  threedrug ART was stable at 62 from 2000
  onwards,the proportion of time spent off all
  ART, having previously taken it, increased from
  3 in 1997/9to 9 in 2003/5.

CD4 increase of gt10 CD4 increase of gt10 CD4 increase of gt10 HIV-1 RNA lt400 copies/ml HIV-1 RNA lt400 copies/ml HIV-1 RNA lt400 copies/ml
OR 95 CI p OR 95 CI p
Age at HAART per year 0.85 0.78-0.92 lt0.001 1.03 0.96-1.10 0.469
CD4 at HAART per 5 0.55 0.47-0.64 lt0.001 1.05 0.93-1.18 0.428
Sex female 1.68 1.01-2.81 0.044 0.97 0.60-1.57 0.905
Calendar year at HAART 2000/2 0.92 0.50-1.70 2.27 1.30-3.96
2003/5 1.12 0.59-2.12 0.833 2.99 1.60-5.59 0.001

• CONCLUSIONS
• Mortality and hospital admission rates continued
  to decline since the introduction of HAART in
  1997
• Viral load suppression 12 months after HAART
  initiation improved over time
• Results suggest a better immunological response
  in girls, but require further investigation
• Low rates of switching to second line therapy
  were observed
• Increased triple class exposure complicates
  longer term clinical management
• Provision of transitional services and continued
  monitoring will be essential as the cohort ages
  into adolescence and adulthood

• RATES OF PROGRESSION TO AIDS AND DEATH
• Rates (per 100 person years) have continued to
  decline since the introduction of HAART
• Year AIDS/deaths (95CI) Deaths (95CI)
• -1996 13.4 (11.4-15.6) 8.3 (6.9-9.8)
• 1997-9 5.7 (4.3-7.5) 1.9 (1.2-2.8)
• 2000-2 3.2 (2.3-4.3) 0.9 (0.6-1.5)
• 2003-5 2.7 (1.9-3.6) 0.6 (0.3-1.1)
• 18 children died in 2003-5
• 7 presented with AIDS and/or died within one
  month
• Of the remaining 11
• - only 3 were on HAART for 6 months prior to
  death
• - primary cause of death was opportunistic
  infections (2), HIV encephalopathy (1), sepsis
  (1), lung disease (1), other (3), and not
  known (3)

PRIOR DRUG CLASS EXPOSURE OVER TIME

• At last follow up, 27 of 5-9, 33 of 10-14, and
  38 of 15 year olds had been exposed to all
  three main classes of HAART

COLLABORATORS We thank staff and families from
the hospitals collaborating inCHIPS/NSHPC, as
well as the UK Department of Health,Bristol-Myers
Squibb, Boehringer-Ingelheim, GlaxoSmithKline,
Roche,Abbott and Gilead for financial
support. CHIPS Steering Committee members Karina
Butler, Sheila Donaghy,David Dunn, Trinh Duong,
Di Gibb, Ali Judd, Hermione Lyall, Janet
Masters,Esse Menson, Vas Novelli, Catherine
Peckham, Andrew Riordan,Mike Sharland, Pat
Tookey, Gareth Tudor-Williams, Gillian Wait.
KEY PAPERS Gibb DM et al. Decline in mortality,
AIDS, and hospital admissions in perinatally
HIV-1 infected children in the United Kingdom and
Ireland. BMJ 2003,3271019. Walker AS et al.
Response to highly active antiretroviral therapy
varies with age the UK and Ireland Collaborative
HIV Paediatric Study. AIDS 2004,181915-1924. Men
son EN et al. Systematic inaccurate prescribing
of paediatric antiretroviral drugs - a good
example of universal bad practice in medicines
for children? BMJ - in press
CONTACT FOR FURTHER INFORMATION Ali Judd MRC
Clinical Trials Unit 222 Euston Road
44 20 7670 4830 London NW1 2DA
a.judd_at_ctu.mrc.ac.uk www.chipscohort.ac.uk