Exposure and response to highly active antiretroviral therapy (HAART) in ART na

1
Exposure and response to highly active
antiretroviral therapy (HAART) in ART naïve
children in the UK and Ireland
Judd A.1, Lee K.J.1, Duong T.1, Walker A.S.1,
Butler K.2, Donaghy S.3, Dunn D.T.1, Lyall H.4,
Masters J.5, Menson E.3, Novelli V.6, Peckham
C.5, Riordan A.7, Sharland M.3, Tookey P.5,
Tudor-Williams G.4, Gibb D.M.1 on behalf of
CHIPS 1MRC Clinical Trials Unit, London, UK,
2Our Lady's Hospital for Sick Children, Dublin,
Ireland, 3St George's Hospital, London, UK, 4St
Mary's Hospital, London, UK, 5Institute for Child
Health, London, UK, 6Great Ormond Street Hospital
for Sick Children, London, UK, 7Royal Liverpool
Children's Hospital, Liverpool, UK
Poster number THPE0106
BACKGROUND The National Study of HIV in Pregnancy
and Childhood (NSHPC) is a voluntary
confidentialactive reporting scheme for
pregnancies in HIV-infected women, babies born to
HIV-infected women, andchildren with HIV
infection, covering the wholeof 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. 41hospitals in the UK and
Ireland currently collaboratein the CHIPS study,
accounting for ?90 of allchildren reported to
the NSHPC in 2005. CHIPS isbeing extended to
the whole of the UK and Irelandduring 2006/7.

• METHODS
• Data are for reports received to end of March
  2006
• Analyses are for all diagnosed children (n1522),
  except HAART exposure response which are for
  CHIPS children only (n1169)
• Crude rates of progression to AIDS and death per
  100 person years at risk were calculated by year
• 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 to undertake joint analyses.
• AIM
• The aim of this analysis was to describe
  characteristics of the CHIPS cohort HAART use in
  previously untreated children and the effect of
  age, sex, and CD4, HIV-1 RNA and year at HAART
  initiation, on response to first line treatment
  at 12 months

AGE GROUP BY YEAR OF REPORT (n1522)

• SOCIODEMOGRAPHICS (n1522)
• 50 female
• 71 black African, 14 white, 15 other
• 51 born in the UK and Ireland, 49 born abroad
• Median age at presentation varied by country of
  birth
• - constant at 0.5 years until 2001, then rose
  to one year in 2004/6, for those born in the UK
  and Ireland
• - increased yearly from 2 years before 1991 to 8
  years in 2004/6 for those born abroad
• 12 identified prospectively from birth, 69
  prior to an AIDS diagnosis, and 19 at AIDS
  diagnosis
• 94 vertically infected, 3 blood transfusion, 3
  other

Year n 363 403 481 535
617 713 796 911 989 987

• Median age increased year on year
• 44 ?10 years in 2005 compared to 11 in 1996

• 12 MONTH IMMUNOLOGICAL AND VIROLOGICAL RESPONSE
  TO HAART (n666 starting HAART naive)
• 78 suppressed viral load lt400 copies/ml in
  2003/5, compared to only 52 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

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 0.80-0.92 lt0.001 1.03 0.97-1.10 0.339
CD4 at HAART per 5 0.56 0.48-0.64 lt0.001 1.03 0.91-1.15 0.659
Sex female 1.56 0.97-2.51 0.067 1.12 0.71-1.76 0.638
Calendar year at HAART 2000/2 1.07 0.59-1.94 1.98 1.16-3.39
2003/5 1.15 0.64-2.09 0.897 3.51 1.94-6.32 0.001

• HAART EXPOSURE AND SWITCHING (n1169)
• 666 children in CHIPS started a HAART
  regimensince 1997 and were ART naïve at the
  start of HAART
• Median age at HAART was 4.8 years (IQR1.5-8.9)
• 93 remained on first line HAART after 12
  months,86 after 24 months, and 79 after 36
  months(in this analysis, first line" 3-4 drug
  HAART allows for 1-2 drug substitutions (if not
  made for viral load, CD4 or clinical failure),
  drug intensifications/ reductions)
• Median time to switching to second line was 7
  years
• Whilst the proportion of child time spent on 3 or
  4drug 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.

• CONCLUSIONS
• The median age of the cohort has increased year
  on year
• AIDS progression and mortality rates continued to
  decline since the introduction of HAART in 1997
• CD4 increases gt10 were more likely in younger
  children and those with lower pre-HAART CD4, as
  found in a previous analysis (Walker et al 2004)
• Viral load suppression 12 months after HAART
  initiation improved with calendar year, but was
  not related to age at HAART, unlike previously
• Low rates of switching to second line therapy
  were observed
• The proportion of child time spent off all ART
  after having previously received it increased
  with calendar year
• The proportion of triple class exposed children
  has been relatively stable over the last five
  years, reflecting the durability of first and
  second line HAART in this cohort
• Provision of transitional services and continued
  monitoring will be essential as the cohort ages
  into adolescence and adulthood

DRUG CLASS EXPOSURE OVER TIME (n1169)

Year n 23 127 187 250
298 359 449 504 443

• At last follow up, 27 of 5-9, 33 of 10-14, and
  36 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.
CHIPS is funded by the UK Department of Health.
Additional support was obtained from
Bristol-Myers Squibb, Boehringer-Ingelheim,
GlaxoSmithKline, Roche, Abbott and
Gilead. CONTACT FOR FURTHER INFORMATION Ali Judd
44 20 7670 4830 MRC Clinical
Trials Unit a.judd_at_ctu.mrc.ac.uk 222
Euston Road London NW1 2DA
KEY PAPERS Gibb DM et al. Decline in mortality,
AIDS, and hospital admissions in perinatally
HIV-1 infected children in the UK and Ireland.
BMJ 2003,3271019. Walker AS et al. Response to
HAART varies with age the UK and Ireland
Collaborative HIV Paediatric Study. AIDS
2004,181915-1924. Doerholt K et al. Outcomes
for HIV-1-infected infants in the UK and Republic
of Ireland in the era of effective antiretroviral
therapy. PIDJ 2006 25 420-426. Menson EN et
al. Underdosing of antiretrovirals in UK and
Irish children with HIV as an example of problems
in prescribing medicines to children, 1997-2005
cohort study. BMJ 2006,3321183-1187
www.chipscohort.ac.uk