Transcript Document

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 George’s Hospital, London; 4 Royal Liverpool Children’s Hospital, Liverpool; 5 St Mary’s Hospital, London; 6 Our Lady’s Hospital for Sick Children, Dublin;
7 Great Ormond Street Hospital, London.
BACKGROUND
HOW THE NSHPC & CHIPS WORK TOGETHER
METHODS
The National Study of HIV in Pregnancy and
Childhood (NSHPC) is a voluntary confidential
reporting scheme for HIV/AIDS diagnoses in pregnant
women and children, covering the whole of the UK and
Ireland.
Children diagnosed with HIV are initially reported to the
NSHPC. Once the infection is confirmed, the NSHPC
informs CHIPS, which sends out detailed annual follow
up questionnaires if the child is seen in a hospital
collaborating in CHIPS. For hospitals not in CHIPS, a
brief annual follow up form is sent out by the NSHPC.
Data are shared between the studies in order to
undertake joint analyses.
 Analyses relating to HAART exposure and response
are confined to children in CHIPS only (n=1065). All
other analyses include all diagnosed children
(n=1439)
 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
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
AIM
study, accounting for 90% of all children currently in the
The aim of this analysis was to describe changes over
NSHPC. CHIPS is being extended to the whole of the
time in demographics, morbidity and mortality, and
UK and Ireland during 2006/7.
exposure and response to HAART, in HIV infected
children in the UK and Ireland between 1996 and 2005.
 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
AGE GROUP BY CALENDAR YEAR OF REPORT
SOCIODEMOGRAPHICS
REGIONAL DISTRIBUTION OF CHILDREN
 50% female
100%
 72% black African, 13% white, 16% other
90%
80%
 55% born in the UK and Ireland, 45% born abroad
 Median age at presentation varied by country of
birth:
0%
N. Ireland
- constant for the UK and Ireland at ~0.5 years
5%
Ireland
23%
Rest of
England
Most children are seen in London hospitals
HAART EXPOSURE AND SWITCHING
5-9
1-4
50%
<1
40%
20%
10%
0%
 13% identified prospectively from birth, 68% prior
to an AIDS diagnosis, and 19% at AIDS diagnosis
66%
London
10-14
60%
30%
- increased from 2 years up to 1991 to 8 years in
2004/5 for those born abroad
1%
Wales
>=15
70%
Percentage
5%
Scotland
96
97
98
99
00
01
02
03
04
05
Year
 Median age of the cohort increasing year on year
 13% 10 years in 1996 compared to 46% in 2005
 94% vertically infected, 3% blood transfusion, 3%
other
12 MONTH IMMUNOLOGICAL AND VIROLOGICAL RESPONSE TO HAART
 595 children in CHIPS started a HAART regimen
since 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
CD4% increase of >10%
HIV-1 RNA <400 copies/ml*
OR†
95% CI
p
OR†
95% CI
p
Age at HAART
per year
0.85
0.78-0.92
<0.001
1.03
0.96-1.10
0.469
 Median time to switching to second line was
7.2 years
CD4% at HAART
per 5%
0.55
0.47-0.64
<0.001
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
 Whilst the proportion of child time spent on three
drug ART was stable at ~62% from 2000 onwards,
the proportion of time spent off all ART, having
previously taken it, increased from 3% in 1997/9
to 9% in 2003/5.
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
2.99
1.60-5.59
0.833
0.001
 76% suppressed viral load <400 copies/ml in 2003/5, compared to only 51% in 1997/9.
*A cut off of <50 copies/ml could not be used due to some hospitals continuing to use the “<400” cut off in recent years. † Multivariable. ‡ Baseline=1997/9
PRIOR DRUG CLASS EXPOSURE OVER TIME
RATES OF PROGRESSION TO AIDS AND DEATH
 Rates (per 100 person years) have continued to
decline since the introduction of HAART:
100%
90%
80%
All 3 classes
Year
AIDS/deaths (95%CI) Deaths (95%CI)
-1996
1997-9
2000-2
2003-5
13.4 (11.4-15.6)
5.7 (4.3-7.5)
3.2 (2.3-4.3)
2.7 (1.9-3.6)
NRTI+PI only
70%
Percentage
NRTI+NNRTI only
60%
NRTI only
50%
40%
30%
20%
10%
0%
97
98
99
00
01
02
03
04
05
Year
 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
8.3
1.9
0.9
0.6
(6.9-9.8)
(1.2-2.8)
(0.6-1.5)
(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)
COLLABORATORS
KEY PAPERS
We thank staff and families from the hospitals collaborating in
CHIPS/NSHPC, as well as the UK Department of Health,
Bristol-Myers Squibb, Boehringer-Ingelheim, GlaxoSmithKline, Roche,
Abbott and Gilead for financial support.
Gibb DM et al. Decline in mortality, AIDS, and hospital admissions in perinatally
HIV-1 infected children in the United Kingdom and Ireland. BMJ 2003,327:1019.
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.
Walker AS et al. Response to highly active antiretroviral therapy varies with age:
the UK and Ireland Collaborative HIV Paediatric Study. AIDS 2004,18:1915-1924.
Menson EN et al. Systematic inaccurate prescribing of paediatric antiretroviral
drugs - a good example of universal bad practice in medicines for children? BMJ in press
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
CONTACT FOR FURTHER INFORMATION
Ali Judd
MRC Clinical Trials Unit
222 Euston Road
London NW1 2DA
+44 20 7670 4830
[email protected]
www.chipscohort.ac.uk