Transcript Children and resistance to HIV: CHIPS data

Children and resistance to
HIV: CHIPS data
Dr Katherine Boyd
on behalf of
Collaborative HIV Paediatric Study (CHIPS) and
the UK HIV Drug Resistance Database
Introduction
• There are over 20 antiretroviral drugs to treat HIV
infected children.
• A lack of age-appropriate formulations and
pharmacokinetic data can result in sub-therapeutic
concentrations.
• Poor adherence can be a problem and cause resistance,
particularly in adolescence.
• Objectives:
1) Possible transmission of resistance.
2) Acquired resistance in children after starting ART.
UK HIV Drug
Resistance Database
• Established in 2001 as a central repository of resistance tests
carried out as part of routine care in the UK.
• Contains all routinely-performed (or within PENTA trials) HIV
drug resistance tests in the UK, 1998-2006, from all
laboratories.
• Data include some patient demographics, dates and locations
of tests, and resistance mutations.
• Drug susceptibility (using the Stanford HIVdb) and HIV
subtype are also available.
CHIPS data
• A multi-centre cohort study of HIV infected children under care in
59 hospitals in the UK & Ireland since 1996.
• 1291 UK children in CHIPS between 1998 and 2006.
• 52% female, 77% black African, 52% born abroad, 95% with
known vertical infection.
• Matched 710 tests in 389 children: 239 children have 1 test, 77
have 2 tests, 35 have 3 tests, and 38 have four or more tests.
• Rates of testing consistent across the UK.
• 2.6% have documented pMTCT.
Use of resistance testing: by
previous ART experience*
Tests before first reported
ART
Tests after first reported
ART
Number of tests (children)
65
(65)
635
(336)
Age at test (years):
Median (IQR)
6.1
(1.0 , 9.1)
10.0
(6.0 , 13.4)
CD4% at test:
Median (IQR)
18
(12 , 24)
21
(12 , 29)
Log10 HIV1-RNA at test
(copies/ml):
Median (IQR)
5.3
(4.8 , 5.7)
4.3
(3.7 , 4.9)
43% HIV subtype C, 19% subtype A, and 9% subtype B
* ART status can not be defined for 10 tests.
Tests prior to starting ART: by year
Starting ART with a resistance test
Starting ART without a resistance test
160
Number of children
140
PENTA 5
120
100
80
60
40
20
0
1998
% of those
starting ART that
had a prior test :
1999
2000
2001
2002
2003
2004
2005
2006
Year starting ART
12.8
5.8
2.6
1.5
3.2
1.9
5.4
18.7 20.3
ART naïve: Evidence of
transmitted drug resistance?
• Children with at least 1 major resistance mutation:
Overall rate = 6/65 (9%).
Age
(yrs)
Born
abroad?
Age (yrs)
presented to
UK services
Mutations*
PI
NRTI
NNRTI
1
0.2
No
Birth
215I
2
0.9
India
0.9
215I
3
2.0
Portugal
2.0
184V 215C 215Y 219E
4
0.4
No
Birth
184I
188L
5
16.1
No
2.3
41L 74V 184V 210W
215Y
101E 181C
190A
6
0.4
No
Birth
47A 84V
41L 67N 70R 210W
215F 215V 219E
* Using Shafer et al. AIDS 2007, Vol. 21.
Tests after starting ART: by year
Child with a resistance test and previous ART
Child with one HIV-RNA > 1000 c/ml with previous ART
450
Number of children
400
350
300
250
200
150
100
50
0
1998
1999
2000
2001
2002
2003
2004
2005
2006
23.1
34.0
43.2
31.9
Year
% of children
with test :
5.3
11.1
14.2
10.4
23.9
Major resistance mutations by year in
tests after the start of ART* (n=635)
PI
NRTI
NNRTI
Any class
% of tests with at least
one major mutation
100
80
60
40
20
0
1998
1999
2000
2001
2002
2003
2004
2005
2006
Year
• 36% of children with resistance to NRTIs had mono/dual therapy compared
to 13% of those who did not.
* Using IAS guidelines Topics in HIV Medicine 2007, Vol. 14.
Prevalence* of resistance to individual drugs
in children after the start of ART (n = 336)
Intermediate level resistance
High level resistance
Prevalence (%)
60
50
40
30
20
10
0
r
r
r
r
r
vi avi avi avi avir avir avir
ne ine ine avir ine ine ovi
i
a
ud itab nos ac vud vud nof
fin uin zan ren pin ran run
l
v
i
e
m tric ida
Ab ido Sta Te
N Saq Ata m p Lo Tip Da
a
Z
A
L
D
Em
PI
* Based only on the last resistance test per child
NRTI
e
in dine enz
p
ir
r
iv ra avi fav
e
E
el
N
D
NNRTI
ART class major resistance* in ART
experienced children (n=336)
Proportion of tests by the
number of resistant classes
Resistance to
0 classes
1 class
2 classes
3 classes
1.0
0.8
0.6
0.4
0.2
0.0
2000
2001
2002
2003
2004
2005
2006
Year
* Based only on the last resistance test per child
* Using IAS guidelines Topics in HIV Medicine 2007, Vol. 14.
Triple class resistance in ART
experienced children
• In CHIPS, 391 children have had triple class exposure.
• Of these, 23 (5.9%) have known triple class resistance
and 137 (35.0%) have resistance to two ART classes.
• Median (IQR) age at tests showing…
triple class resistance: 10.3 (6.0 , 13.3) years.
resistance to two ART classes : 9.1 (5.5 , 12.7) years
• Half of those with resistance to at least 2 classes were
≥13 years old.
Discussion and Conclusions:
Resistance in ART naïve children
• There is little use of resistance testing in ART naïve
children. Slightly higher use in ART experienced children
possibly increasing over time.
• Possible evidence of some transmitted resistance from
mother to child.
Discussion and Conclusions:
Resistance after starting ART
• Resistance to NRTIs may reflect use of mono/dual
therapy prior to HAART.
• Higher resistance to NNRTIs reflects the relatively rapid
emergence of resistance to these drugs compared to
boosted PIs.
• Resistance, in particular triple class, will affect future
drug choices for adolescents transferring to adult clinics.
Low use of T-20 and Raltegravir in children.
Acknowledgements
• CHIPS centres, staff, and children
• NSHPC
• The UK Collaborative Group on HIV drug
Resistance
www.chipscohort.ac.uk