data from the collaborative hiv paediatric study (chips) reports up to march 2013*

Data from the

Collaborative HIV Paediatric Study

(CHIPS)

Reports up to March 2013*

* Numbers are based on reports received rather than children seen to the end of March 2013. 2012/13 data are subject to reporting delay and may therefore be incomplete.

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 – 65 clinics in the UK and Ireland that care for HIV-infected

children, some of whom are enrolled in PENTA trials (PENTA 16 BREATHER and PENTA 18 KONCERT)

– the National Study of HIV in Pregnancy and Childhood (NSHPC), and

– the MRC Clinical Trials Unit

Follow-up status of 1835 children enrolled in CHIPS

1111

111

2092 32

469

0

200

400

600

800

1000

1200

Still in CHIPSfollow-up

Transferred tonon-CHIPS

clinics

Left country Lost tofollow-up

Transferred toadult care

Died*

Num

ber

of c

hild

ren

* 94 deaths prior to 2008, 6 in 2008, 8 in 2009, 2 in 2010, 1 in 2011+

Age group by year first presented to medical services in the UK/Ireland

(N=1835*)

* 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)

Up to 2008 2009 2010 2011 2012+ Total

At birth 164 (10%) 6 (8%) 3 (5%) 5 (11%) 1 (20%) 179 (10%) <1 yr 341 (21%) 6 (8%) 5 (9%) 2 (5%) 0 (0%) 354 (19%) 1-4 yrs 499 (30%) 13 (17%) 7 (12%) 6 (14%) 0 (0%) 525 (29%) 5-9 yrs 409 (25%) 21 (27%) 12 (21%) 5 (11%) 2 (40%) 449 (24%) 10-14 yrs 226 (14%) 25 (32%) 25 (44%) 18 (41%) 2 (40%) 296 (16%) ≥15 yrs 13 (1%) 6 (8%) 5 (9%) 8 (18%) 0 (0%) 32 (2%)

Total 1652 (100%) 77 (100%) 57 (100%) 44 (100%) 5 (100%) 1835 (100%)

Age* of children in paediatricfollow-up by year, 1996-2012

*Age is taken to be age at start of the year, or age at presentation if child presented during that year.Note: Data are for children and young people receiving paediatric care; those who have transferred toadult clinics are not included here.

Year No. Median (IQR) -------------------- Age group ------------------ age < 1 yr 1-4 yrs 5-9 yrs 10-14 yrs 15 yrs

1996 357 5.1 (2.9-7.6) 26(7%) 146(41%) 144(40%) 40 (11%) 1 (0%) 1997 414 5.4 (3.1-8.2) 29(7%) 152(37%) 174(42%) 55 (13%) 4 (1%) 1998 493 6 (3.2-8.9) 22(4%) 172(35%) 211(43%) 78 (16%) 10 (2%) 1999 559 6.5 (3.7-9.8) 26(5%) 172(31%) 232(42%) 111(20%) 18 (3%) 2000 658 7.2 (4-10.4) 23(3%) 196(30%) 257(39%) 143(22%) 39 (6%) 2001 757 7.6 (4.5-10.9) 20(3%) 202(27%) 291(38%) 197(26%) 47 (6%) 2002 859 8 (5-11.7) 21(2%) 190(22%) 344(40%) 237(28%) 67 (8%) 2003 987 8.5 (5.6-12) 22(2%) 188(19%) 388(39%) 300(30%) 89 (9%) 2004 1088 8.9 (5.9-12.4) 19(2%) 187(17%) 417(38%) 347(32%) 118(11%) 2005 1164 9.5 (6.5-12.9) 18(2%) 155(13%) 447(38%) 392(34%) 152(13%) 2006 1237 10.2 (6.9-13.4) 17(1%) 151(12%) 433(35%) 436(35%) 200(16%) 2007 1289 10.8 (7.6-14) 10(1%) 142(11%) 394(31%) 510(40%) 233(18%) 2008 1306 11.4 (8.2-14.5) 13(1%) 126(10%) 362(28%) 521(40%) 284(22%) 2009 1310 12.1 (9-15.1) 9 (1%) 105(8%) 320(24%) 539(41%) 337(26%) 2010 1274 12.8 (9.5-15.4) 7 (1%) 82 (6%) 259(20%) 564(44%) 362(28%) 2011 1250 13.5 (10.1-15.9) 6 (0%) 60 (5%) 230(18%) 526(42%) 428(34%) 2012 957 13.6 (10.5-15.9) 5 (1%) 37 (4%) 169(18%) 395(41%) 351(37%)

0%

20%

40%

60%

80%

100%1

99

6

19

97

19

98

19

99

20

00

20

01

20

02

20

03

20

04

20

05

20

06

20

07

20

08

20

09

20

10

20

11

20

12

Year

Percentage

15+

10-14

5-9

1-4

<1

N 357 414 493 559 658 757 859 987 1088 1164 1237 1289 1306 1310 1274 1250 957

Age* of children in paediatric follow-up by year, 1996-2012

*Age is taken to be age at start of the year, or age at presentation if child presented during that year.Note: Data are for children and young people receiving paediatric care; those who have transferred toadult clinics are not included here.

All hospital admissions during 2000-2011*

* Retrospective data on admissions not collected for children from clinics joining since Aug 2003. 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 2012/13 are incomplete and are not presented.

2000 603 165 27 327 0.59 2001 667 178 27 313 0.51 2002 729 157 22 246 0.36 2003 833 187 22 320 0.42 2004 955 182 19 287 0.34 2005 1085 177 16 289 0.29 2006 1138 163 14 243 0.23 2007 1170 145 12 215 0.20 2008 1201 147 12 217 0.19 2009 1193 120 10 153 0.14 2010 1162 91 8 132 0.12 2011 1139 103 9 138 0.14

Year Number Number Proportion Total Rate (# children children admitted number admissions seen admitted admissions per pyr)

Year Viral load (copies/ml) ≤50 or ≤lower

assay limit** 1997/2000 104/222 (47%) 2001/2003 135/227 (59%) 2004/2006 185/257 (72%)

2007/2009 171/231 (74%) 2010- 68/93 (73%)

Total 663/1030 (64%)

* Response is based on the viral load value nearest 12 months (+/-3 months) after cART initiation**158/663 (25%) of undetectable results had a lower limit of detection >50 but ≤400c/ml and are included here.

Viral load suppression 12 months* after starting cART naïve, all agesN=1030 with measurements available (291 missing)


assay limit** 1997/2000 98/213 (46%) 2001/2003 127/214 (59%) 2004/2006 156/218 (72%) 2007/2009 137/188 (73%)

2010- 43/62 (69%)

Total 561/895 (63%)


Viral load suppression 12 months* after starting cART naïve at age ≤12 years

N=895 with measurements available (241 missing)


assay limit** 1997/2000 6/9 (67%) 2001/2003 8/13 (62%) 2004/2006 29/39 (74%) 2007/2009 34/43 (79%)

2010- 25/31 (81%)

Total 102/135(76%)


Viral load suppression 12 months* after starting cART naïve at age ≥13 years

N=135 with measurements available (50 missing)

Age at cART <2 years 2-4 years 5-9 years 10+ years

Time to viral rebound (>1000c/ml) for children suppressing viral load ≤400c/ml within 12 months of starting cART naïve, 2000-2003

0.0

00

.25

0.5

00

.75

1.0

0

Pro

port

ion

su

ppre

sse

d

48 28 20 17 11Age = 10+ yrs88 70 62 49 45Age = 5-9 yrs61 48 46 41 36Age = 2-4 yrs65 51 43 42 41Age = < 2 yrs

Number at risk

0 1 2 3 4

Time (years) suppressed on cART

Age at cART <2 years 2-4 years 5-9 years 10+ years

Time to viral rebound (>1000c/ml) for children suppressing viral load ≤400c/ml within 12 months of starting cART naïve, 2004-2011

0.0

00

.25

0.5

00

.75

1.0

0

Pro

port

ion

su

ppre

sse

d

271 183 114 73 37Age = 10+ yrs169 137 118 86 60Age = 5-9 yrs69 56 45 36 31Age = 2-4 yrs105 74 55 52 39Age = < 2 yrs

Number at risk

0 1 2 3 4

Time (years) suppressed on cART

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 of ≥3 ART drugs (regardless of reason for switch) or a switch of 2 ART drugs with reported reasons being ‘failure’ (immunological/virological/clinical failure or resistance), with viral load >50 copies/ml.3 58/318 had missing viral load after 12 months on 2nd line, and a further 64/318 had missing viral load after 12 months on 1st line. 4 53 (16%) undetectable results had a lower limit of detection >50 but ≤400c/ml and are included.

Year starting 2nd-line cART

Number (%) ≤50c/ml or ≤lower assay limit4 12 months after starting....

1st line cART 2nd line cART

1997/2000 2/16 (13%) 6/16 (38%)

2001/2003 11/55 (20%) 26/49 (53%)

2004/2006 18/60 (30%) 40/68 (59%)

2007/2009 39/70 (56%) 47/81 (58%)

2010- 22/53 (42%) 33/46 (72%)

Total 92/254 (36%) 152/260 (58%)

Viral load 12 months1 after starting 1st and 2nd line cART for those switching2 to 2nd line

(N=318 children switched to 2nd line after at least 12 months on 1st line3)

Data on 1131 children who are in active follow-up

(1111 in CHIPS clinics and 20 who have transferred to non-CHIPS clinics)

Those who have died, lost to follow-up, left the UK & Ireland or transferred to adult care are excluded.

Demographics (N=1131) (Data provided by NSHPC)

• 585 (52%) are female

• 539 (48%) born UK/Ireland, 575 (51%) born abroad (place of birth not known for 17 children)

• Ethnicity:

• Diagnosis of maternal infection (N=1085 vertically infected):

White 62 (5%)

Black African 893 (79%)

Black other 10 (1%)

Indian 15 (1%)

Mixed 116 (10%)

Other 13 (1%)

Not known 22 (2%)

Known after delivery 899 (83%)

Known before delivery 145 (13%)

Not known 41 (4%)

564 (50%)London

47 (4%) Scotland

439 (39%)Rest of England

61 (5%)Ireland

14 (1%)Wales

Regional distribution ofmain follow-up clinic for 1131 children alive and followed up in CHIPS

Children who have died, lost to follow-up, left the UK & Ireland or transferred to adult care are excluded

5 (<1%)N. Ireland

Year of last follow-up (N=1131)

41

363

198

529

0

100

200

300

400

500

600

Up to 2010 2011 Jan-Jun 2012 Since July 2012

Num

ber

of c

hild

ren

Clinical stage by age at last follow-up (N=1131)

No. of children < 2 years 2-4 years 5-9 years 10-14 years ≥15 years Total (%)

Stage N/A 10 (100%) 31 (67%) 146 (65%) 267 (53%) 180 (52%) 634 (56%)

Stage B 0 (0%) 4 (9%) 25 (11%) 115 (23%) 90 (26%) 234 (21%)

Stage C 0 (0%) 11 (24%) 54 (24%) 120 (24%) 78 (22%) 263 (23%)

Total 10 (100%) 46 (100%) 225 (100%) 502 (100%) 348 (100%) 1131 (100%)

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

% o

f ch

ildr

en

Antiretroviral drug experience N=1090 children with follow-up since January 2011

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

% o

f ch

ildr

en

No. of children < 2 years 2-4 years 5-9 years 10-14 years ≥15 years Total (%)

Naive 0 (0%) 3 (7%) 39 (18%) 59 (12%) 24 (7%) 125 (11%)

1-4 drugs 9 (90%) 24 (56%) 112 (52%) 201 (41%) 83 (25%) 429 (39%)

5-7 drugs 1 (10%) 16 (37%) 54 (25%) 147 (30%) 116 (34%) 334 (31%)

8+ drugs 0 (0%) 0 (0%) 10 (5%) 78 (16%) 114 (34%) 202 (19%)

Total 10 (100%) 43 (100%) 215 (100%) 485 (100%) 337 (100%) 1090 (100%)

ART at last follow-upN=903 children with follow-up since Jan 2011 were on treatment

17 on mono, 35 on dual, 792 on 3-drug, 53 on 4-drug and 6 on 5(+)-drug therapy

72173312

444415

0

100

200

300

400

500

600

PI+N

RT

I

NN

RT

I+N

RT

I

PI+N

NR

TI

3 N

RT

I

2 N

RT

I

1 PI 2P

I

Oth

er

Num

ber

of c

hild

ren

Most recent CD4% (N=1048)Children followed up since January 2011 (missing for 42 children)

No. of children 0-10% 11-20% 21-30% >30%

Naïve 0 (0%) 26 (20%) 56 (17%) 37 (7%)

On mono 1 (4%) 4 (3%) 4 (1%) 7 (1%)

On dual 2 (8%) 5 (4%) 14 (4%) 13 (2%)

On initial cART 3 (12%) 36 (27%) 133 (40%) 262 (47%)

On subseq cART 14 (56%) 45 (34%) 104 (31%) 224 (40%)

Off ART 5 (20%) 17 (13%) 25 (7%) 11 (2%)

Total 25 (100%) 133 (100%) 336 (100%) 554 (100%)

0

50

100

150

200

250

300

Num

ber

of c

hild

ren

Most recent CD4 count (N=1048)Children ≥ 5 years old followed up since Jan 2011 (missing for 38 children)

No. of children 0-200 201-350 351-500 501-1000 >1000

Naïve 0 (0%) 6 (10%) 37 (19%) 64 (13%) 9 (4%)

On mono 1 (3%) 2 (3%) 3 (2%) 7 (1%) 3 (1%)

On dual 2 (5%) 2 (3%) 4 (2%) 20 (4%) 6 (3%)

On initial cART 3 (8%) 20 (34%) 71 (37%) 201 (40%) 102 (50%)

On subseq cART 23 (62%) 22 (37%) 57 (30%) 190 (38%) 84 (41%)

Off ART 8 (22%) 7 (12%) 19 (10%) 19 (4%) 1 (<1%)

Total 37 (100%) 59 (100%) 191 (100%) 501 (100%) 205 (100%)

0

50

100

150

200

250

Nu

mb

er o

f ch

ild

ren

No. of children≤50c/ml (or ≤lower

assay limit**)

>50c/ml (or>lower assay limit) – 100,000c/ml

>100,000c/ml

Naïve 4 (1%) 103 (30%) 12 (41%)

On mono 8 (1%) 8 (2%) 0 (0%)

On dual 23 (3%) 11 (3%) 0 (0%)

On initial cART 360 (53%) 78 (22%) 1 (3%)

On subseq cART 276 (41%) 104 (30%) 7 (24%)

Off ART 4 (1%) 45 (13%) 9 (31%)

Total 675 (100%) 349 (100%) 29 (100%)

0

50

100

150

200

250

300

350

400

Nu

mb

er o

f ch

ild

ren

Most recent viral load (N=1053)Children followed up since January 2011 (missing for 37 children)

**4/675 (<1%) of undetectable results had a lower limit of detection >50 but ≤400c/ml and are included here.

Outcome 1: Retention in carePercentage of newly diagnosed children in 2010 who had ≥2 CD4

and ≥2 VL measurements within 12 months of diagnosis

Perc

enta

ge (

%)

Notes: The y axis shows percentages, and at the top of each bar shows the number of children

Outcome 2: Retention on ARTPercentage of patients newly starting ART in 2009 who were still on

ART in 2010

Perc

enta

ge (

%)


Outcome 3A: Immune status in children <5 yrs Percentage of children aged <5 years with ≥1 CD4 measure ≥25%

in 2010, by ART status

Perc

enta

ge (

%)


Outcome 3B: Immune status in children ≥5 years Percentage of children aged ≥5 years with ≥1 CD4 measure

≥350 cells/mm3 in 2010, by ART status

Perc

enta

ge (

%)


Outcome 4A: Virologic response on ART Percentage of children on ART with ≥2 VL measures <50c/ml

and <400c/ml, in 2010

Perc

enta

ge (

%)


Dotted bar: VL <50c/ml Plain bar: VL <400 c/ml

Outcome 4B: Virologic response on ART, age≥13yrs

Percentage of young people aged ≥13 years on ART with ≥2 VLmeasures <50c/ml, and <400 c/ml, in 2010

Perc

enta

ge (

%)


Dotted bar: VL <50c/ml Plain bar: VL <400 c/ml

Outcome 5: Description of deaths in 2010

Two paediatric deaths were reported to CHIPS in 2010.

(1)Aged 20.1 years, cause of death was: Respiratory – unspecified. First presented aged 12 years with CD4% of 1% and 7 cells/mm3. At time of death was taking DRV and exposed to a total of 9 drugs. Was seen 5 times in the 12 months prior to death.

(2)Aged 9.8 years, causes of death were: Tuberculosis meningitis, advanced HIV disease / general deterioration/HIV encephalopathy / dementia/ADC/ encephalitis. First presented aged 7.1 years with CD4% of 33% and 644 cells/mm3. At time of death was taking 3TC+ABC+EFV and exposed to total of 3 drugs. Was seen 4 times in the 12 months prior to death.

Involvement in PENTA trialsBREATHER (PENTA 16) enrolment is ongoing in 2013. Please contact [email protected] for further details about BREATHER and KONCERT.

KONCERT BREATHERLondon – 13 Oxford – 2 London – 14 Leicester – 2Birmingham – 1 Liverpool – 1 Birmingham – 2 Bristol – 2 Bristol – 1 Ireland – 1 Ireland – 3 Nottingham – 2Nottingham – 2

Recent PENTA publications:

•Harrison L, Ananworanich J, Hamadache D, Compagnucci A, Penazzato M, et al. on behalf of the Paediatric European Network

for Treatment of AIDS (PENTA) 11 Trial Team Adherence to Antiretroviral Therapy and Acceptability of Planned Treatment

Interruptions in HIV-Infected Children. AIDS Behav. 2013 January; 17(1): 193–202.

•Bunupuradah T, Duong T, Compagnucci A, McMaster P, Bernardi S, et al. on behalf of the PENTA 11 Extension Study Group.

Outcomes after reinitiating antiretroviral therapy in children randomized to planned treatment interruptions in the PENTA 11

Study. AIDS. 2012 Nov 6.

•Bastiaans DET, Forcat S, Lyall HEG, Cressey TR, Chalermpantmetagul S, et al. Pharmacokinetics of 100/25 mg

lopinavir/ritonavir tablets in children when dosed twice daily according to FDA weight bands. 4th International Workshop on

HIV pediatrics 2012. July 20-21, 2012. L'Enfant Plaza Hotel, Washington DC, USA. Poster 41.

•Mbisa JL, Hue S, Buckton AJ, Myers RE, Duiculescu D, et al. Phylodynamic and Phylogeographic Patterns of the HIV-1

Subtype F1 Parenteral Epidemic in Romania. AIDS Res Hum Retroviruses 2012 Jan 18.

mailto:[email protected]

Recent CHIPS-related publications(based either wholly or partly on CHIPS data)

• European Pregnancy and Paediatric HIV Cohort Collaboration (EPPICC) study group in EuroCoord. Use of combination neonatal prophylaxis for the prevention of mother-to-child transmission of HIV infection in European high-risk infants. AIDS – in press.

• Donegan K, Doerholt K, Judd A, Lyall H, Menson E, Butler K, Tookey P, Riordan A, Shingadia D, Tudor-Williams G, Gibb DM, Walker AS, on behalf of the Collaborative HIV Paediatric Study (CHIPS). Lopinavir dosing in HIV-infected children in the UK and Ireland. PIDJ 2013; 32: 45-50.

• Wittkop L on behalf of the EuroCoord-CHAIN subtype project team. Effect of HIV-1 subtypes on virological and immunological response to initial combination antiretroviral therapy (cART) – a European multicohort study. CROI, Atlanta, 2013

• Duong T et al. Long-term virological outcomes in HIV-infected children on ART in the UK/ Ireland. 17th International Workshop on HIV Observational Databases, Croatia, 2013.

• Rojo Conejo P on behalf of the PLATO II project team of COHERE. Higher rates of triple class virologic failure in perinatally HIV-infected teenagers compared to heterosexually infected young adults in the PLATO II study. 17Th International Workshop on HIV Observational Databases, Croatia, 2013.

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:www.chipscohort.ac.uk

data from the collaborative hiv paediatric study (chips) reports up to march 2013*

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