1. Collaborative HIV Paediatric Study
Data from the
Collaborative HIV Paediatric Study
(CHIPS)
Reports up to April 2016*
* Numbers are based on reports received rather than children seen to the end of April /16 data are subject to reporting delay and may therefore be incomplete.

2. Background to CHIPS
The Collaborative HIV Paediatric Study (CHIPS) was established in April 2000 and is a multi-centre cohort study of HIV-1 infected children in the UK and Ireland.
The collaboration is between
67 clinics in the UK and Ireland that care for HIV-infected children
the National Study of HIV in Pregnancy and Childhood (NSHPC), and
the MRC Clinical Trials Unit at UCL

3. Follow-up status of 1951 children enrolled in CHIPS
Deaths in paediatric care: 94 deaths prior to 2008, 6 in 2008, 6 in 2009, 2 in 2010, 2 in 2011

4. Age group by year first presented to medical services in the UK/Ireland (1944*)
Up to Total
At birth (10%) (8%) (13%) (0%) (8%) (9%)
<1 yr (17%) (3%) (6%) (0%) (3%) (16%)
1-4 yrs (29%) (11%) (6%) (30%) 8 (22%) (28%)
5-9 yrs (26%) (15%) (31%) (20%) 13 (35%) (26%)
10-14 yrs (16%) (45%) (44%) (30%) 11 (30%) (18%)
>=15 yrs (2%) (18%) (0%) (20%) 1 (3%) (2%)
Total (100%) 65 (100%) 32 (100%) 20 (100%) 37 (100%) (100%)
* Includes all children (those still in follow-up and those who have died, lost to follow-up, left the UK & Ireland or transferred to adult care), 7 are missing date first presented to medical services

5. Age of UK/Irish cohort of patients with HIV acquired in childhood, 1996-2015
Year No. Median (IQR) Age group
age < 1 yr yrs yrs yrs yrs ≥20 yrs
( ) 33(10%) 146(44%) 124(37%) (9%) (0%) (0%)
( ) 47(12%) 141(37%) 148(39%) 45(12%) (1%) (0%)
( ) 38(8%) 171(37%) 178(39%) 64(14%) (1%) (0%) ( ) 32(6%) 180(34%) 209(40%) 95(18%) (2%) (0%)
( ) 35(6%) 193(31%) 240(38%) 129(21%) (4%) (0%) ( ) 34(5%) 194(27%) 276(39%) 168(24%) (6%) (0%)
( ) 37(5%) 191(23%) 320(39%) 206(25%) (7%) (0%)
( ) 35(4%) 179(19%) 390(41%) 264(28%) (8%) (1%)
( ) 32(3%) 188(17%) 408(38%) 321(30%) 114(11%) (1%) ( ) 33(3%) 169(14%) 437(37%) 362(31%) 158(13%) (2%) ( ) 30(2%) 160(13%) 434(34%) 403(32%) 208(16%) (3%)
( ) 25(2%) 137(10%) 414(30%) 474(35%) 251(18%) (4%) ( ) 18(1%) (9%) 365(25%) 536(37%) 303(21%) (6%) ( ) 17(1%) (8%) 338(22%) 540(36%) 370(25%) (8%) ( ) 10(1%) (6%) 292(19%) 569(37%) 409(26%) 177(11%) ( ) 10(1%) (5%) 248(15%) 572(36%) 462(29%) 240(15%) ( ) 8(0%) (3%) 216(13%) 524(32%) 533(33%) 301(18%) ( ) 3(0%) (2%) 185(11%) 439(27%) 595(36%) 382(23%) ( ) 2(0%) (2%) (9%) 392(24%) 591(36%) 488(29%)
( ) 2(0%) (1%) (7%) 323(19%) 610(37%) 585(35%)
Note: Data are for all children and young people alive who ever presented to medical services in the UK/Ireland, including children who have since transferred to adult care; those who subsequently died or were lost to follow-up are excluded from the year of death or loss to follow-up. All paediatric patients included, regardless of mode of acquisition (94% perinatal). CHIPS includes all diagnosed HIV-infected children known to be living in the UK/Ireland, of whom ~50% were born abroad. Data for 2015 are incomplete as subject to reporting delay.

6. Age of UK/Irish cohort of patients with HIV acquired in childhood, 1996-2015
Note: Data are for all children and young people alive who ever presented to medical services in the UK/Ireland, including children who have since transferred to adult care; those who subsequently died or were lost to follow-up are excluded from the year of death or loss to follow-up. All paediatric patients included, regardless of mode of acquisition (94% perinatal). CHIPS includes all diagnosed HIV-infected children known to be living in the UK/Ireland, of whom ~50% were born abroad. Data for 2015 are incomplete as subject to reporting delay.

7. Age of UK/Irish cohort of patients with HIV acquired in childhood & in paediatric follow-up,
Year No. Median (IQR) Age group
age < 1 yr yrs yrs yrs yrs ≥20 yrs
(2-7) (3%) 16(46%) 13(37%) 5(14%) (0%) 0(0%)
(1-6.5) (19%) 12(38%) 11(34%) (6%) (3%) 0(0%)
(1-8) (6%) 21(41%) 17(33%) 8(16%) (4%) 0(0%)
(3-9) (5%) 64(32%) 87(43%) 36(18%) (2%) 0(0%)
(3-10) (2%) 103(39%) 82(31%) 61(23%) (5%) 0(0%)
(3-9) (1%) 114(48%) 64(27%) 44(18%) (5%) 0(0%)
(3-7) (3%) 116(50%) 74(32%) 27(12%) (4%) 0(0%)
(3-7) (3%) 121(37%) 138(43%) 41(13%) (4%) 1(0%)
(4-8) (3%) 144(34%) 201(48%) 47(11%) (4%) 3(1%)
(4-8) (2%) 135(25%) 294(54%) 77(14%) (4%) 4(1%)
(5-9) (2%) 122(22%) 337(60%) 70(13%) (3%) 2(0%)
(5-10) (1%) 108(18%) 328(56%) 128(22%) (3%) 3(1%)
(6-10) (1%) 105(16%) 324(48%) 210(31%) (3%) 4(1%)
(7-11) (0%) 90(13%) 298(42%) 282(40%) (5%) 6(1%)
(7-12) (0%) 77(10%) 243(32%) 392(52%) (5%) 5(1%)
(8-13) (1%) (7%) 214(27%) 442(56%) (9%) 4(1%)
(9-14) (0%) (4%) 190(23%) 438(54%) 142(17%) 7(1%)
(10-15) (0%) (3%) 164(20%) 407(48%) 232(28%) 11(1%)
(11-16) (0%) (3%) 127(15%) 356(41%) 341(39%) 20(2%) (12-17) (0%) (2%) 102(12%) 282(32%) 440(50%) 35(4%)
Note: Data are for all children and young people alive who were ever in paediatric follow-up from 1996 onwards; those who subsequently died or were lost to follow-up or transferred to adult care are excluded from the year this happened onwards. All paediatric patients are included, regardless of mode of acquisition (94% perinatal). CHIPS includes all diagnosed HIV-infected children known to be living in the UK/Ireland, of whom ~50% were born abroad. Data for 2015 are incomplete as subject to reporting delay.

8. Age of UK/Irish cohort of patients with HIV acquired in childhood & in paediatric follow-up, N=
Note: Data are for all children and young people alive who were ever in paediatric follow-up from 1996 onwards; those who subsequently died or were lost to follow-up or transferred to adult care are excluded from the year this happened onwards. All paediatric patients are included, regardless of mode of acquisition (94% perinatal). CHIPS includes all diagnosed HIV-infected children known to be living in the UK/Ireland, of whom ~50% were born abroad. Data for 2015 are incomplete as subject to reporting delay.

9. All hospital admissions during 2000-2014
Year Number Number Proportion Total Rate (#
children children admitted number admissions
seen* admitted (%) admissions per 100 pyr)
* Retrospective data on admissions not collected for children from clinics joining since Aug These children are counted from when they begin prospective follow-up in CHIPS.
Admissions may be underreported for children in shared care where only information from the main CHIPS follow-up clinic is reported. Data for 2014 are incomplete as subject to reporting delay.

10. Viral load suppression 12 months. after starting cART naïve
Viral load suppression 12 months* after starting cART naïve**, all ages N=1131 with measurements available
Year Viral load (copies/ml)
≤50 or ≤lower
assay limit***
1997/ /101 (26%)
2000/ /338 (39%)
2005/ /419 (62%)
/273 (74%)
Total / (55%)
* Response is based on the viral load value nearest 12 months (+/-3 months) after cART initiation
** Newly defined as: first line therapy is 3 or more drugs across two classes or 3NRTIs including ABC
***47/622 (8%) of undetectable results had a lower limit of detection >50 but ≤400c/ml and are included here.

11. Viral load suppression 12 months. after starting cART naïve
Viral load suppression 12 months* after starting cART naïve**, at age ≤12 years N=872 with measurements available
Year Viral load (copies/ml)
≤50 or ≤lower
assay limit***
1997/ /93 (24%)
2000/ /305 (39%)
2005/ /329 (60%)
/145 (73%)
Total /872 (51%)
* Response is based on the viral load value nearest 12 months (+/-3 months) after cART initiation
** Newly defined as: first line therapy is 3 or more drugs across two classes or 3NRTIs including ABC
*** 37/444 (8%) of undetectable results had a lower limit of detection >50 but ≤400c/ml and are included here.

12. Viral load suppression 12 months. after starting cART naïve
Viral load suppression 12 months* after starting cART naïve**, at age ≥13 years N=259 with measurements available
Year Viral load (copies/ml)
≤50 or ≤lower
assay limit***
1997/ /8 (50%)
2000/ /33 (42%)
2005/ /90 (70%)
/128 (76%)
Total /259 (69%)
* Response is based on the viral load value nearest 12 months (+/-3 months) after cART initiation
** Newly defined as: first line therapy is 3 or more drugs across two classes or 3NRTIs including ABC
*** 10/178 (6%) of undetectable results had a lower limit of detection >50 but ≤400c/ml and are included here.

13. Time to viral rebound (>1000c/ml) for children suppressing viral load ≤400c/ml within 12 months of starting cART naïve,

14. Time to viral rebound (>1000c/ml) for children suppressing viral load ≤400c/ml within 12 months of starting cART naïve,

15. Time to viral rebound (>1000c/ml) for children suppressing viral load ≤400c/ml within 12 months of starting cART naïve,

16. Number (%) ≤50c/ml or ≤lower assay limit4 12 months after starting....
Viral load 12 months1 after starting 1st and 2nd line cART for those switching2 to 2nd line (N=441 children switched to 2nd line after at least 12 months on 1st line3)
Year starting 2nd-line cART
Number (%) ≤50c/ml or ≤lower assay limit4 12 months after starting....
1st line cART
2nd line cART
1997/2000
3/13
(23%)
4/11
(36%)
2001/2003
16/52
(31%)
28/48
(58%)
2004/2006
26/70
(37%)
52/82
(63%)
2007/2009
47/83
(57%)
64/91
(70%)
2010-
89/146
(61%)
112/155
(72%)
Total
181/364
(50%)
260/387
(67%)
1 Response is based on viral load value closest to 12 months (+/-3 months) after starting 1st/ 2nd line, for those starting cART naive and remaining on 1st line for at least 12 months and 2nd line for at least 12 months.
2 Defined as any switch across drug class or change/addition of PI drug or addition of new drug class.
3 77/441 had missing viral load after 12 months on 1st line, and a further 54/441 had missing viral load after 12 months on 2nd line.
4 24/441 (5%) undetectable results had a lower limit of detection >50 but ≤400c/ml and are included.

17. Data on 905 children who are in active follow-up
Those who have died, lost to follow-up, left the UK & Ireland or transferred to adult care are excluded.

18. Demographics (N=905) (Data provided by NSHPC)
480 (53%) are female
435 (48%) born UK/Ireland, 450 (50%) born abroad (not known for 18 children)
Ethnicity:
Diagnosis of maternal infection (N=843 vertically infected):
White 47
(5%)
Black African
703
(78%)
Black other 7
(1%)
Indian 12
Mixed 96
(11%)
Other 10
Not known 30
(3%)
Known after delivery
695
(82%)
Known before delivery
118
(14%)
Not known 30
(4%)

19. Regional distribution of main follow-up clinic for 905 children alive and followed up in CHIPS
32 (4%)
Scotland
5 (1%)
Northern
Ireland
384 (42%)
Rest of England
52 (6%)
Ireland
12 (1%)
Wales
417 (46%)
London
Children who have died, lost to follow-up, left the UK & Ireland or transferred to adult care are excluded

20. Year of last follow-up (N=905)

21. Clinical stage by age at last follow-up (N=877)
No. of children
< 2 years
2-4 years
5-9 years
10-14 years
≥15 years
Total
(%)
Stage N/A 4
(80%) 15
(65%) 75
(61%)
173
(53%)
(43%)
440
(50%)
Stage B 1
(20%) 5
(22%) 21
(17%) 77
(23%)
128
(32%)
232
(26%)
Stage C
(0%) 3
(13%) 26
(21%) 79
(24%) 97
205
(100%) 23
122
329
398
877

22. Antiretroviral drug experience N=828 children with follow-up since January 2014
No. of children
< 2 years
2-4 years
5-9 years
10-14 years
≥15 years
Total
(%)
Naive
(0%) 2
(10%) 9
(8%) 23 16
(4%) 50
(6%)
1-4 drugs
(50%) 10 46
(41%)
125 89
(23%)
272
(33%)
5-7 drugs 8
(40%)
103
(34%)
147
(38%)
306
(37%)
8+ drugs 12
(11%) 54
(18%)
134
(35%)
200
(24%) 4
(100%) 20
113
305
386
828

23. ART at last follow-up N=778 children with follow-up since Jan 2014 were on treatment 29 on mono, 42 on dual, 658 on 3-drug, 47 on 4-drug and 2 on 5(+)-drug therapy

24. Most recent CD4% (N=754) Children followed up since January 2014
No. of children
0-10%
11-20%
21-30%
>30%
Total
Naïve
(0%) 5
(12%) 25
(58%) 13
(30%) 43
(100%)
On mono
(23%) 10
(45%) 7
(32%) 22
On dual 4
(11%)
(36%) 19
(53%) 36
On initial cART
(4%) 69
154
(66%)
233
On subseq cART 6
(2%) 26
(7%) 95
(24%)
266
(68%)
393
Off ART 1
(22%)
(37%) 27
Note: Row percentages now provided. Initial cART newly defined as first line therapy is 3 or more drugs across two classes or 3NRTIs including Abacavir. Subsequent cART defined as any switch across drug class or change/addition of PI drug or addition of new drug class.

25. Most recent CD4 count (N=755) Children ≥ 5 years old followed up since Jan 2014
No. of children
0-200
>1000
Total
Naïve 1
(2%) 7
(16%) 30
(67%) 6
(13%) 45
(100%)
On mono
(5%) 3
(14%) 11
(52%) 21
On dual
(3%) 2
(6%)
(8%) 19
(53%)
(31%) 36
On initial cART
(1%) 8 29
(12%)
145
(62%) 50
(21%)
234
On subseq cART 18 42
(11%)
211
(54%)
114
(29%)
392
Off ART 4
(15%)
(26%)
(41%)
(7%) 27
Note: Row percentages now provided. Initial cART newly defined as first line therapy is 3 or more drugs across two classes or 3NRTIs including Abacavir. Subsequent cART defined as any switch across drug class or change/addition of PI drug or addition of new drug class.

26. Most recent viral load (N=723) Children followed up since January 2014
No. of children
≤50c/ml (or ≤lower assay limit**)
>50c/ml (or>lower assay limit) – 100,000c/ml
>100,000c/ml
Total
Naïve 4
(8%) 41
(85%) 3
(6%) 48
(100%)
On mono 14
(64%) 8
(36%)
(0%) 22
On dual 25
(71%) 10
(29%) 35
On initial cART
188 34
(15%)
222
On subseq cART
299
(81%) 70
(19%)
369
Off ART 2
(7%) 20
(74%) 5
(18%) 27
Note: Row percentages now provided. Initial cART newly defined as first line therapy is 3 or more drugs across two classes or 3NRTIs including Abacavir. Subsequent cART defined as any switch across drug class or change/addition of PI drug or addition of new drug class.
**6/620 (<1%) of undetectable results had a lower limit of detection >50 but ≤400c/ml and are included here.

27. Outcome 1: Retention in care Percentage of newly diagnosed children in 2013 who had ≥2 CD4 and ≥2 VL measurements within 12 months of diagnosis
Notes: The y axis shows percentages, and at the top of each bar shows the number of children

28. Outcome 2: Retention on ART Percentage of patients newly starting ART in 2012 who were still on ART in 2013
Notes: The y axis shows percentages, and at the top of each bar shows the number of children

29. Outcome 3A: Immune status in children <5 yrs Percentage of children aged <5 years with ≥1 CD4 measure ≥25% in 2013, by ART status
Notes: The y axis shows percentages, and at the top of each bar shows the number of children

30. Outcome 3B: Immune status in children ≥5 years Percentage of children aged ≥5 years with ≥1 CD4 measure ≥350 cells/mm3 in 2013, by ART status
Notes: The y axis shows percentages, and at the top of each bar shows the number of children

31. Outcome 4A: Virological response on ART Percentage of children on ART with ≥2 VL measures <50c/ml and <400c/ml, in 2013
Dotted bar: VL <400c/ml Plain bar: VL <50 c/ml
Notes: The y axis shows percentages, and at the top of each bar shows the number of children

32. Outcome 4B: Virological response on ART, age≥13yrs Percentage of young people aged ≥13 years on ART with ≥2 VL measures <50c/ml, and <400 c/ml, in 2013
Dotted bar: VL <400c/ml Plain bar: VL <50 c/ml
Notes: The y axis shows percentages, and at the top of each bar shows the number of children

33. Outcome 5: Description of deaths since 2013
No paediatric deaths since 2013

34. Involvement in PENTA trials
Some patients from CHIPS are currently involved in BREATHER (PENTA 16) – patients are being followed up until July 2016.
Centres with patients in BREATHER
Evelina – 3 St George’s – GOSH - 7
Leicester – 2 Nottingham – 1
Birmingham – 4 Bristol – 1
Dublin – 3
Enrolments to new PENTA trials will start soon. If you are interested in participating in SMILE (NRTI-sparing regimen (elvitegravir+darunavir/r) in years who are clinically stable and virologically suppressed), please contact
Recent PENTA publications/presentations:
S. Bernays, S. Paparini, D. Gibb & J. Seeley When information does not suffice: young people living with HIV and communication about ART adherence in the clinic. Vulnerable Children and Youth Studies: An International Interdisciplinary Journal for Research, Policy and Care. E-pub Dec 2015
Harrison L., Melvin A., Fiscus S., Saidi Y., Nastouli E., Harper L., Compagnucci A., Babiker A., McKinney R., Gibb D., Tudor-Williams G., HIV-1 Drug Resistance and Second-line Treatment in Children Randomized to Switch at Low versus Higher RNA Thresholds, JAIDS 2015 Sep 1;70(1).
Once- versus twice-daily lopinavir/ritonavir in HIV-1 infected children: a randomised controlled trial (KONCERT/PENTA18/ANRS150). AIDS 2015, 29:  

35. Recent CHIPS-related publications / presentations (based either wholly or partly on CHIPS data)
Writing group for the Kids to Adults Working Group and Data Management and Harmonisation Group in EuroCoord. Children and young people with perinatal HIV in Europe: epidemiological situation in 2014 and implications for the future. Eurosurveillance, 2016;21(10):ppi=30162.
The European Pregnancy and Paediatric HIV Cohort Collaboration (EPPICC) in EuroCoord. Safety of darunavir and atazanavir in HIV-infected children in Europe and Thailand. Antiviral Therapy, 2015 Nov 12.
Turkova, A, Chappell E, Judd A et al., Prevalence, incidence, and associated risk factors of tuberculosis in children with HIV living in the UK and Ireland (CHIPS): a cohort study. Lancet HIV, (12): p. e530-e539.
Goodall RL, Collins IJ, Childs T, Foster C, Ene L, Smit C, Kahlert C, Judd A, Gibb DM, on behalf of the European Pregnancy and Paediatric HIV Cohort Collaboration (EPPICC).  Durability of first-line antiretroviral therapy (ART) in children in the European Pregnancy and Paediatric HIV Cohort Collaboration (EPPICC).  8th International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention, Vancouver 2015 (poster TUPEB304).
Le Prevost M, Melvin D, Nunn A, Arenas-Pinto A, Evangeli M, Foster C, Winston A, Gibb DM, Judd A.  Anxiety and depression in young people with perinatal HIV and their HIV-negative siblings.  7th International Workshop on HIV Pediatrics, Vancouver 2015 (oral).
Le Prevost M, Judd A.  Life after CHIPS: CHIPS and AALPHI update.  9thAnnual Conference of the Children’s HIV Association (CHIVA), Leicester 2015 (oral).
Judd A, Nunn A, Melvin D, Foster C, Winston A, Le Prevost M, Sturgeon K, Gibb DM, Arenas-Pinto A.  Neurocognitive function in perinatally HIV-infected young people and HIV-negative siblings in England.  9th Annual Conference of the Children’s HIV Association (CHIVA), Leicester 2015 (oral).
Hawkins A, Evangeli M, Sturgeon K, Le Prevost M, Judd A.  Predictors of within-indivudual episodic antiretroviral adherence in young people living with perinatally acquired HIV.  AIDS Impact 2015 Conference, Amsterdam (oral).

36. For further information on CHIPS, please visit:
Acknowledgements
We thank the families and staff at hospitals which participate in CHIPS. CHIPS is funded by the NHS (London Specialised Commissioning Group), and has received additional support from Bristol-Myers Squibb, Boehringer Ingelheim, GlaxoSmithKline, Roche, Abbott, and Gilead.
For further information on CHIPS, please visit: