1. Data from the Collaborative HIV Paediatric Study (CHIPS) Reports up to March 2009* * Numbers are based on reports received rather than children seen to the end of March 2009. 2008/9 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 –63 clinics in the UK and Ireland that care for HIV-infected children, 16 of whom have 75 children currently enrolled in PENTA trials –the National Study of HIV in Pregnancy and Childhood (NSHPC), and –the MRC Clinical Trials Unit

3. Follow-up status of 1560 children enrolled in CHIPS * 86 deaths prior to 2006, 4 in 2006, 3 in 2007, 8 in 2008+

4. Age/year at first presentation to medical services in the UK/Ireland (N=1560*) * 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 2005 2006 2007 2008+ Total At birth 133 (10%) 7 (7%) 6 (7%) 5 (14%) 151 (10%) <1 yrs 300 (22%) 16 (16%) 10 (12%) 5 (14%) 331 (21%) 1-4 yrs 422 (32%) 25 (25%) 16 (19%) 7 (20%) 470 (30%) 5-9 yrs 326 (24%) 27 (27%) 32 (37%) 6 (17%) 391 (25%) >=10 yrs 158 (12%) 25 (25%) 22 (26%) 12 (34%) 217 (14%) Total 1339 (100%) 100 (100%) 86 (100%) 35 (100%) 1560 (100%)

5. Age distribution* of children in follow-up by year, 1996-2008 * 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 411 5.6 (3.1-8.3) 27(7%) 151(37%) 174(42%) 55(13%) 4(1%) 1998 489 6 (3.3-8.9) 21(4%) 169(35%) 211(43%) 78(16%) 10(2%) 1999 552 6.6 (3.7-9.8) 23(4%) 170(31%) 229(41%) 112(20%) 18(3%) 2000 645 7.2 (4.1-10.5) 21(3%) 188(29%) 254(39%) 143(22%) 39(6%) 2001 742 7.8 (4.7-11.1) 17(2%) 193(26%) 288(39%) 197(27%) 47(6%) 2002 842 8.1 (5.1-11.7) 21(2%) 180(21%) 339(40%) 236(28%) 66(8%) 2003 966 8.5 (5.7-12.1) 21(2%) 178(18%) 380(39%) 300(31%) 87(9%) 2004 1059 9.2 (6-12.4) 19(2%) 177(17%) 404(38%) 343(32%) 116(11%) 2005 1128 9.6 (6.6-12.9) 17(2%) 147(13%) 429(38%) 390(35%) 145(13%) 2006 1185 10.3 (7-13.5) 14(1%) 140(12%) 412(35%) 428(36%) 191(16%) 2007 1203 10.9 (7.6-14.1) 10(1%) 126(10%) 360(30%) 484(40%) 223(19%) 2008 1130 11.2 (7.9-14.4) 11(1%) 107(9%) 320(28%) 461(41%) 231(20%)

6. Age distribution* of children in follow-up by year, 1996-2008 N 357 411 489 552 645 742 842 966 1059 1128 1185 1203 1130 * 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 2000-2007* * 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 2008/9 are incomplete and are not presented. 2000 593 164 28 325 0.59 2001 654 175 27 309 0.51 2002 715 156 22 243 0.37 2003 817 182 22 314 0.42 2004 935 181 19 284 0.34 2005 1061 176 17 286 0.30 2006 1106 159 14 236 0.23 2007 1113 136 12 200 0.19 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=763 with measurements available (236 missing) Year HIV-1 RNA (copies/ml) ≤50 or ≤lower assay limit** 1997/99 73/161 (45%) 2000/02 109/195 (56%) 2003/05 190/278 (68%) 2006- 95/129 (74%) Total 467/763 (61%) * Response is based on the HIV-1 RNA value nearest 12 months (+/-3 months) after HAART initiation **139/467 (30%) 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, 2004-2008

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 56/207 had missing HIV-1 RNA after 12 months on 2nd line, and a further 23/151 had missing HIV-1 RNA after 12 months on 1st line. 4 30 (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 1997/20026/49 (12%)23/54 (43%) 2003-200826/79 (33%)59/97 (61%) Total32/128 (25%)82/151 (54%) HIV-1 RNA 12 months 1 after starting 1st and 2nd line HAART for those switching 2 to 2nd line ( N=207 children switched to 2 nd line after at least 12 months on 1 st line 3 )

12. Data on 1169 children who are alive and in active follow-up (1161 in CHIPS clinics and 8 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=1169) (Data provided by NSHPC) 601 (51%) are female 583 (50%) born UK/Ireland, 581 (50%) born abroad (place of birth not known for 5 children) Ethnicity: Diagnosis of maternal infection (N=1137 vertically infected): White 84(7 %) Black African 913(78 %) Black other 11(1 %) Indian SC 17(1 %) Mixed 123(11 %) Other 11(1 %) Not known 10(1 %) Known after delivery 966(85 %) Known before delivery 140(12 %) Not known 31(3 %)

14. 660 (56%) London 43 (4%) Scotland 389 (33%) Rest of England 57 (5%) Ireland 15 (1%) Wales Regional distribution of main follow-up clinic for 1169 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=1169)

16. Clinical stage by age at last follow-up (N=1169) No. of children< 2 years2-4 years5-9 years≥10 yearsTotal(%) Stage N/A 17 (53%)55 (57%)186 (53%)303 (44%)561(48%) Stage B 2 (6%)14 (14%)71 (20%)221 (32%)308(26%) Stage C 13 (41%)28 (29%)93 (27%)166 (24%)300(26%) Total 32 (100%)97 (100%)350 (100%)690 (100%)1169(100%)

17. Antiretroviral drug experience N=1143 children with follow-up since January 2007 No. of children< 2 years2-4 years5-9 years≥10 yearsTotal(%) Naive 7 (22%)31 (33%)80 (24%)100 (15%)218(19%) 1-4 drugs 23 (72%)51 (55%)172 (51%)272 (40%)518(45%) 5-7 drugs 2 (6%)10 (11%)75 (22%)185 (27%)272(24%) 8+ drugs 0 (0%)1 (1%)10 (3%)124 (18%)135(12%)

18. ART at last follow-up N=819 children with follow-up since Jan 2007 were on treatment 6 on mono, 21 on dual, 712 on 3-drug, 70 on 4-drug and 10 on 5(+)-drug therapy

19. Most recent CD4% (N=1126) Children followed up since January 2007 (missing for 17 children)

20. Most recent CD4 count (N=1004) Children > 5 years old followed up since Jan 2007 (missing for 16 children)

21. Most recent HIV-1 RNA (N=1123) Children followed up since January 2007 (missing for 20 children) **14/1123 (1%) of undetectable results had a lower limit of detection >50 but ≤400c/ml and are included here.

22. Involvement in PENTA trials* London - 22 children in PENPACT 1, 25 in PENTA 11 (1 in adult care), 6 in PENTA 15 (1 left country). Direct linking centres - 4 children in PENPACT 1, 1 in PENTA 11, 2 in PENTA 15. Midlands – 1 child in PENTA 11, 5 in PENTA 15. South West & South Wales – 5 children in PENPACT 1. North West & North Wales - 2 children in PENPACT 1, 1 (in adult care) in PENTA 11, 1 (in adult care) in PENTA 15. North East – 2 children in PENPACT 1 (1 in to adult care). Ireland – 3 children in PENPACT 1. * Location of last clinic reported to CHIPS

23. Recent CHIPS-related publications (based either wholly or partly on CHIPS data) Foster C et al (2009) Young people in the UK and Ireland with perinatally acquired HIV: the paediatric legacy for adult services. AIDS Patient Care & STDs, 23 (3):159-166. Goetghebuer T et al (2009) Effect of early antiretroviral therapy on the risk of AIDS/death in HIV infected infants: the European Infant Collaborative Study. AIDS, 23; 597-604. Judd A et al (2009) Vertically acquired HIV diagnosed in adolescence and early adulthood in the UK and Ireland: findings from national surveillance – HIV Medicine, 10: 253-256. Judd A et al (2009) Effect of tenofovir disoproxil fumarate (TDF) on risk of renal impairment in HIV-1 infected children on antiretroviral therapy: nested case-control study. 16th CROI, Montreal (poster). Kekitiinwa A et al (2008) Differences in factors associated with initial growth, CD4 and viral load response to ART in Ugandan and UK/ Irish HIV-infected children. JAIDS, 49(4): 384-392. Riordan A et al (2009) Tenofovir use in human immunodeficiency virus -1 infected children in the United Kingdom and Ireland. PIDJ, 28(3):204-9 Walker AS et al (2009) To overdose or underdose? The question of Kaletra in children in the UK/Irish Collaborative HIV Paediatric Study (CHIPS). Ninth International Congress on Drug Therapy in HIV Infection, Glasgow (oral).

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