1. Data from the Collaborative HIV Paediatric Study (CHIPS) Reports up to March 2010* * Numbers are based on reports received rather than children seen to the end of March 2010. 2009/10 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 as a multi-centre cohort study of HIV-1 infected children in the UK and Ireland. The collaboration is between –70 clinics in the UK and Ireland that care for HIV-infected children, 5 of whom have 28 children currently enrolled in ongoing PENTA trials (PENTA 11) –the National Study of HIV in Pregnancy and Childhood (NSHPC), and –the MRC Clinical Trials Unit

3. Follow-up status of 1650 children enrolled in CHIPS * 91 deaths prior to 2007, 1 in 2007, 6 in 2008, 8 in 2009+

4. Age/year at first presentation to medical services in the UK/Ireland (N=1650*) * 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 2006 2007 2008 2009+ Total At birth 144 (10%) 6 (6%) 6 (10%) 3 (7%) 159 (10%) <1 yrs 317 (22%) 10 (10%) 8 (14%) 3 (7%) 338 (20%) 1-4 yrs 453 (31%) 18 (19%) 15 (26%) 8 (19%) 494 (30%) 5-9 yrs 355 (24%) 36 (37%) 9 (16%) 9 (21%) 409 (25%) >=10 yrs 183 (13%) 27 (28%) 20 (34%) 20 (47%) 250 (15%) Total 1452 (100%) 97 (100%) 58 (100%) 43 (100%) 1650 (100%)

5. Age distribution* of children in follow-up by year, 1996-2009 * Age is taken to be age at start of the year, or age at presentation if child presented during that year Year No. Median (IQR) ----------------- Age groups ----------------- age  1 yr 2-4 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 413 5.5 (3.1-8.2) 28(7%) 152(37%) 174(42%) 55(13%) 4(1%) 1998 491 6.0 (3.3-8.9) 21(4%) 171(35%) 211(43%) 78(16%) 10(2%) 1999 555 6.6 (3.7-9.8) 24(4%) 170(31%) 231(42%) 112(20%) 18(3%) 2000 649 7.2 (4.0-10.5) 21(3%) 190(29%) 256(39%) 143(22%) 39(6%) 2001 748 7.7 (4.5-11.1) 19(3%) 196(26%) 289(39%) 197(26%) 47(6%) 2002 848 8.1 (5.1-11.7) 21(2%) 184(22%) 341(40%) 236(28%) 66(8%) 2003 973 8.5 (5.7-12.1) 21(2%) 181(19%) 384(39%) 299(31%) 88(9%) 2004 1070 9.1 (6.0-12.4) 19(2%) 181(17%) 408(38%) 344(32%) 118(11%) 2005 1144 9.6 (6.6-12.9) 18(2%) 149(13%) 436(38%) 391(34%) 150(13%) 2006 1208 10.2 (6.9-13.5) 14(1%) 145(12%) 422(35%) 430(36%) 197(16%) 2007 1251 10.8 (7.6-14.1) 10(1%) 133(11%) 381(30%) 497(40%) 230(18%) 2008 1232 11.5 (8.2-14.6) 12(1%) 113(9%) 340(28%) 495(40%) 272(22%) 2009 1098 11.9 (8.8-14.8) 9(1%) 91(8%) 280(26%) 463(42%) 255(23%)

6. N 357 413 491 555 649 748 848 973 1070 1144 1208 1251 1232 1098 Age distribution* of children in follow-up by year, 1996-2009 * Age is taken to be age at start of the year, or age at presentation if child presented during that year

7. All hospital admissions during 2000-2008* * 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 2009/10 are incomplete and are not presented. 2000 596 164 28 325 0.59 2001 659 176 27 311 0.51 2002 720 156 22 243 0.36 2003 822 184 22 317 0.42 2004 942 181 19 284 0.34 2005 1069 177 17 289 0.30 2006 1118 161 14 241 0.23 2007 1141 141 12 210 0.20 2008 1138 136 12 202 0.20 Year Number Number Proportion Total Rate (# children children admitted number admissions seen admitted admissions per pyr)

8. HIV-1 RNA suppression 12 months * after starting HAART naïve N=831 with measurements available (275 missing) Year HIV-1 RNA (copies/ml) ≤50 or ≤lower assay limit** 1997/2000 104/222 (47%) 2001/2003 135/227 (59%) 2004/2006 181/253 (72%) 2007- 92/129 (71%) Total 512/831 (62%) * Response is based on the HIV-1 RNA value nearest 12 months (+/-3 months) after HAART initiation **147/512 (29%) of undetectable results had a lower limit of detection >50 but ≤400c/ml and are included here.

9. Age at HAART <2 years 2-4 years 5-9 years 10+ years Time to viral rebound (>1000c/ml) for children suppressing HIV-1 RNA ≤400c/ml within 12 months of starting HAART naïve, 2000-2003

10. Age at HAART <2 years 2-4 years 5-9 years 10+ years Time to viral rebound (>1000c/ml) for children suppressing HIV-1 RNA ≤400c/ml within 12 months of starting HAART naïve, 2004-2009

11. 1 Response is based on HIV-1 RNA value closest to 12 months (+/-3 months) after starting 1st/ 2nd line, for those starting HAART 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 HIV-1 RNA >50 copies/ml. 3 65/236 had missing HIV-1 RNA after 12 months on 2nd line, and a further 42/236 had missing HIV-1 RNA after 12 months on 1st line. 4 41 (11%) undetectable results had a lower limit of detection >50 but ≤400c/ml and are included. Year starting 2 nd -line HAART Number (%) ≤50c/ml or ≤lower assay limit 4 12 months after starting.... 1 st line HAART2 nd line HAART 1997/200313/71 (18%)32/65 (49%) 2004-200952/123 (42%)63/106 (59%) Total65/194 (34%)95/171 (56%) HIV-1 RNA 12 months 1 after starting 1st and 2nd line HAART for those switching 2 to 2nd line ( N=236 children switched to 2 nd line after at least 12 months on 1 st line 3 )

12. Data on 1245 children who are alive and in active follow-up (1241 in CHIPS clinics and 4 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.

13. Demographics (N=1245) (Data provided by NSHPC) 641 (51%) are female 602 (48%) born UK/Ireland, 637 (51%) born abroad (place of birth not known for 6 children) Ethnicity: Diagnosis of maternal infection (N=1208 vertically infected): White 83(7%) Black African 982(79%) Black other 14(1%) Indian SC 16(1%) Mixed 128(10%) Other 13(1%) Not known 9(1%) Known after delivery1020(84%) Known before delivery 149(12%) Not known 39(3%)

14. 697 (56%) London 46 (4%) Scotland 422 (34%) Rest of England 59 (5%) Ireland 16 (1%) Wales Regional distribution of main follow-up clinic for 1245 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 (0%) N. Ireland

15. Year of last follow-up (N=1245)

16. Clinical stage by age at last follow-up (N=1245) No. of children< 2 years2-4 years5-9 years≥10 yearsTotal(%) Stage N/A 21 (70%)48 (58%)189 (57%)359 (45%)617(50%) Stage B 1 (3%)11 (13%)59 (18%)243 (30%)314(25%) Stage C 8 (27%)24 (29%)85 (26%)197 (25%)314(25%) Total 30 (100%) 83 (100%)333 (100%)777 (100%)1245(100%)

17. Antiretroviral drug experience N=1189 children with follow-up since January 2008 No. of children< 2 years2-4 years5-9 years≥10 yearsTotal(%) Naive 6 (21%)13 (16%)76 (24%)99 (13%)194(16%) 1-4 drugs 20 (71%)59 (72%)170 (53%)302 (40%)551(46%) 5-7 drugs 2 (7%) 9 (11%)65 (20%)220 (29%)296(25%) 8+ drugs 0 (0%)1 (1%)7 (2%)140 (18%)148(12%)

18. ART at last follow-up N=877 children with follow-up since Jan 2008 were on treatment 7 on mono(6 on LPV/r, 1 on ATZ/r), 34 on dual, 770 on 3-drug, 57 on 4-drug and 9 on 5(+)-drug therapy

19. Most recent CD4% (N=1170) Children followed up since January 2008 (missing for 19 children)

20. Most recent CD4 count (N=1060) Children > 5 years old followed up since Jan 2008 (missing for 18 children)

21. Most recent HIV-1 RNA (N=1172) Children followed up since January 2008 (missing for 17 children) **15/589 (3%) of undetectable results had a lower limit of detection >50 but ≤400c/ml and are included here.

22. Involvement in PENTA trials* PENTA 11 - Long term follow up London - 25 Direct linking centres - 1 Midlands – 1 North West & North Wales - 1 (in adult care) PENPACT 1: 38 children. Currently under analysis. PENTA 15: 14 children. Manuscript in press (Antiviral Therapy) PENTA 18 (KONCERT) and PENTA 16 (BREATHER): To start randomisation this year * Location of last clinic reported to CHIPS

23. Recent CHIPS-related publications (based either wholly or partly on CHIPS data) Judd A, Boyd K et al. Effect of Tenofovir Disoproxil Fumarate (TDF) on risk of renal abnormality in HIV-1 infected children on antiretroviral therapy: a nested case-control study. AIDS 2010; 24(4): 525-534. HIV Paediatric Prognostic Markers Collaborative Study (HPPMCS). Discordance between CD4 cell count and CD4 percentage: implications for when to start antiretroviral therapy in HIV-1 infected children. AIDS 2010; 24(8): 1213–1217. Payne H, Heath P et al. Prevalence of vaccine-preventable infections among HIV- infected children in the UK and Ireland over 12 years, 1997-2007 (ESPID 2010 Poster) Boyd K, Walker S et al. The Prevalence of Darunavir Associated Mutations in PI-naive and PI-experienced HIV-1 Infected Children in the UK. (17th Conference on Retroviruses and Opportunistic infections 2010 Poster). Doerholt K, Boyd K et al. Paediatric HIV Projection for the next 5 years – informing service planning & commissioning (RCPCH 2010 Oral presentation)

24. Acknowledgements We thank the families and staff at hospitals which participate in CHIPS. CHIPS is funded by the Department of Health, 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