Transcript presentation - Collaborative HIV Paediatric Study (CHIPS)

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
Poster number THPE0106
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
BACKGROUND
HOW THE NSHPC & CHIPS WORK TOGETHER
METHODS
The National Study of HIV in Pregnancy and
Childhood (NSHPC) is a voluntary confidential
active reporting scheme for pregnancies in HIV-infected
women, babies born to HIV-infected women, and
children with HIV infection, 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.
 Data are for reports received to end of March 2006
The Collaborative HIV Paediatric Study (CHIPS)
is a multicentre cohort study of HIV infected children
under care in the UK and Ireland since 1996. 41
hospitals in the UK and Ireland currently collaborate
in the CHIPS study, accounting for 90% of all
children reported to the NSHPC in 2005. CHIPS is
being extended to the whole of the UK and Ireland
during 2006/7.
REGIONAL DISTRIBUTION (n=1522)
 Analyses are for all diagnosed children (n=1522),
except HAART exposure & response which are for
CHIPS children only (n=1169)
 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
AIM
HAART. All odds ratios (ORs) are adjusted for: age,
CD4% and HIV-1 RNA at HAART initiation; sex; CDC
The aim of this analysis was to describe: characteristics of
B/C events prior to HAART; number of drugs in the
the CHIPS cohort; HAART use in previously untreated
initial HAART regimen; year started HAART; and
children; and the effect of age, sex, and CD4%, HIV-1 RNA
timing of response measurements
and year at HAART initiation, on response to first line
treatment at 12 months
AGE GROUP BY YEAR OF REPORT (n=1522)
SOCIODEMOGRAPHICS (n=1522)
 50% female
100%
 71% black African, 14% white, 15% other
 51% born in the UK and Ireland, 49% born abroad
- constant at ~0.5 years until 2001, then rose to one
year in 2004/6, for those born in the UK and Ireland
24%
Rest of
England
>=15
70%
 Median age at presentation varied by country of
birth:
0%
N.
Ireland
80%
Percentage
4%
Scotland
6%
Ireland
90%
10-14
60%
5-9
50%
1-4
<1
40%
30%
20%
- increased yearly from 2 years before 1991 to 8
years in 2004/6 for those born abroad
1%
Wales
10%
0%
 12% identified prospectively from birth, 69% prior to
an AIDS diagnosis, and 19% at AIDS diagnosis
64%
London
 94% vertically infected, 3% blood transfusion, 3%
other
RATES OF PROGRESSION TO AIDS AND DEATH
(n=1522)
AIDS/deaths (95%CI) Deaths (95%CI)
1996
1997-9
2000-2
2003-5
13.3 (11.3-15.5)
5.7 (4.3-7.4)
3.0 (2.2-4.1)
2.5 (1.8-3.4)
8.2
1.9
0.9
0.6
96
97
98
99
00
01
02
03
04
n
363
403
481
535
617
713
796
911
989
05
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 (n=666 starting HAART naive)
 Rates (per 100 person years) have continued to
decline since the introduction of HAART:
Year
Year
CD4% increase of >10%
(6.9-9.8)
(1.2-2.8)
(0.6-1.5)
(0.3-1.0)
HIV-1 RNA <400 copies/ml*
OR†
95% CI
p
OR†
95% CI
p
Age at HAART
per year
0.85
0.80-0.92
<0.001
1.03
0.97-1.10
0.339
CD4% at HAART
per 5%
0.56
0.48-0.64
<0.001
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
 20 children died in 2003-5:
Calendar year at HAART‡
2000/2
1.07
0.59-1.94
1.98
1.16-3.39
 9 presented with AIDS and/or died within one month
 Of the remaining 11:
2003/5
1.15
0.64-2.09
0.897
3.51
1.94-6.32
0.001
- only 4 were on HAART for 6+ months prior to death

78%
suppressed
viral
load
<400
copies/ml
in
2003/5,
compared
to
only
52%
in
1997/9.
- primary cause of death: OI (2), HIV encephalopathy
(1), sepsis (1), lung disease (1), other (4), unknown (2) *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
HAART EXPOSURE AND SWITCHING (n=1169)
DRUG CLASS EXPOSURE OVER TIME (n=1169)
90%
 Median time to switching to second line was 7 years
 Whilst the proportion of child time spent on 3 or 4
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.
NRTI+PI only
70%
Percentage
(*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)
All 3 classes
80%
 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
 The median age of the cohort has increased year on
year
100%
 666 children in CHIPS started a HAART regimen
since 1997 and were ART naïve at the start of HAART
NRTI+NNRTI only
60%
NRTI only
50%
40%
30%
10%
97
98
99
00
01
02
03
04
05
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
KEY PAPERS
We thank staff and families from the hospitals collaborating in
CHIPS/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.
Gibb DM et al. Decline in mortality, AIDS, and hospital admissions in perinatally
HIV-1 infected children in the UK and Ireland. BMJ 2003,327:1019.
CONTACT FOR FURTHER INFORMATION
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.
Ali Judd
MRC Clinical Trials Unit
222 Euston Road
London NW1 2DA
+44 20 7670 4830
[email protected]
www.chipscohort.ac.uk
 AIDS progression and mortality rates continued to
decline since the introduction of HAART in 1997
 CD4% increases >10% 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
20%
0%
Year
n
CONCLUSIONS
Walker AS et al. Response to HAART varies with age: the UK and Ireland
Collaborative HIV Paediatric Study. AIDS 2004,18:1915-1924.
Menson EN et al. Underdosing of antiretrovirals in UK and Irish children with
HIV as an example of problems in prescribing medicines to children, 19972005: cohort study. BMJ 2006,332:1183-1187
 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