1. Data from the Collaborative HIV Paediatric Study (CHIPS) Reports up to March 2012* * Numbers are based on reports received rather than children seen to the end of March 2012. 2011/12 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 –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

3. Follow-up status of 1791 children enrolled in CHIPS * 94 deaths prior to 2008, 6 in 2008, 8 in 2009, 1 in 2010, 1 in 2011+

4. Age group by year first presented to medical services in the UK/Ireland (N=1791*) * 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+ Total At birth 165 (10%) 6 (8%) 2 (4%) 4 (15%) 177 (10%) <1 yrs 340 (21%) 6 (8%) 3 (6%) 1 (4%) 350 (20%) 1-4 yrs 493 (30%) 13 (18%) 7 (14%) 3 (12%) 516 (29%) 5-9 yrs 407 (25%) 19 (27%) 9 (18%) 4 (15%) 439 (25%) 10-14 yrs 226 (14%) 21 (30%) 23 (46%) 11 (42%) 281 (16%) ≥15 yrs 13 (1%) 6 (8%) 6 (12%) 3 (12%) 28 (2%) Total 1664 (100%) 71 (100%) 50 (100%) 26 (100%) 1791 (100%)

5. Age* of children in paediatric follow-up by year, 1996-2011 *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 to adult 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(<1%) 1997 414 5.4 (3.1-8.2) 29 (7%) 152(37%) 174(42%) 55(13%) 4 (1%) 1998 493 6.0 (3.2-8.9) 22 (4%) 172(35%) 211(43%) 78(16%) 10 (2%) 1999 558 6.5 (3.7-9.8) 25 (4%) 172(31%) 231(41%) 112(20%) 18 (3%) 2000 655 7.2 (4.0-10.5) 23 (4%) 194(30%) 256(39%) 143(22%) 39 (6%) 2001 754 7.6 (4.5-11.0) 20 (3%) 200(27%) 290(38%) 197(26%) 47 (6%) 2002 856 8.0 (5.0-11.7) 21 (2%) 188(22%) 343(40%) 237(28%) 67 (8%) 2003 982 8.5 (5.7-12.1) 22 (2%) 185(19%) 386(39%) 300(31%) 89 (9%) 2004 1081 9.1 (5.9-12.4) 19 (2%) 185(17%) 413(38%) 345(32%) 119(11%) 2005 1156 9.5 (6.5-12.9) 18 (2%) 152(13%) 443(38%) 391(34%) 152(13%) 2006 1229 10.2 (6.9-13.5) 17 (1%) 151(12%) 429(35%) 432(35%) 200(16%) 2007 1280 10.8 (7.6-14.0) 10 (1%) 142(11%) 390(30%) 505(39%) 233(18%) 2008 1289 11.4 (8.2-14.5) 13 (1%) 125(10%) 358(28%) 510(40%) 283(22%) 2009 1277 12.2 (8.8-15.0) 10 (1%) 103 (8%) 318(25%) 517(40%) 329(26%) 2010 1208 12.8 (9.3-15.4) 7 (1%) 79 (7%) 250(21%) 532(44%) 340(28%) 2011 1063 13.1 (9.8-15.5) 5(<1%) 53 (5%) 217(20%) 459(43%) 329(31%)

6. N 357 414 493 558 655 754 856 982 1081 1156 1229 1280 1289 1277 1208 1063 Age* of children in paediatric follow-up by year, 1996-2011 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 to adult clinics are not included here.

7. All hospital admissions during 2000-2010* * 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 2011/12 are incomplete and are not presented. 2000 602 165 27% 327 0.59 2001 665 178 27% 313 0.51 2002 727 157 22% 246 0.36 2003 830 187 23% 320 0.42 2004 951 182 19% 287 0.34 2005 1080 177 16% 289 0.29 2006 1135 163 14% 243 0.23 2007 1167 145 12% 215 0.20 2008 1193 147 12% 217 0.19 2009 1169 119 10% 148 0.14 2010 1110 84 8% 122 0.12 Year Number Number Proportion Total Rate (# children children admitted number admissions seen admitted admissions per pyr)

8. 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%) 2007/2008 112/159 (70%) 2009- 84/103 (82%) Total 620/968 (64%) * Response is based on the viral load value nearest 12 months (+/-3 months) after cART initiation **155/620 (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 ages N=968 with measurements available (284 missing)

9. Year Viral load (copies/ml) ≤50 or ≤lower assay limit** 1997/2000 98/213 (46%) 2001/2003 127/214 (59%) 2004/2006 156/218 (72%) 2007/2008 88/129 (68%) 2009- 62/78 (79%) Total 531/852 (62%) * Response is based on the viral load value nearest 12 months (+/-3 months) after cART initiation **143/531 (27%) 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 at age ≤12 years N=852 with measurements available (234 missing)

10. Year Viral load (copies/ml) ≤50 or ≤lower assay limit** 1997/2000 6/9 (67%) 2001/2003 8/13 (62%) 2004/2006 29/39 (74%) 2007/2008 24/30 (80%) 2009- 22/25 (88%) Total 89/116 (77%) * Response is based on the viral load value nearest 12 months (+/-3 months) after cART initiation **12/89 (13%) 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 at age ≥13 years N=116 with measurements available (50 missing)

11. 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

12. 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

13. 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 68/300 had missing viral load after 12 months on 2nd line, and a further 57/300 had missing viral load after 12 months on 1st line. 4 49 (16%) undetectable results had a lower limit of detection >50 but ≤400c/ml and are included. Year starting 2 nd -line cART Number (%) ≤50c/ml or ≤lower assay limit 4 12 months after starting.... 1 st line cART2 nd line cART 1997/20002/16 (13%)6/16 (38%) 2001/200311/55 (20%)26/49 (53%) 2004/200618/59 (31%)39/67 (58%) 2007/200825/48 (52%)31/51 (61%) 2009+32/65 (49%)29/49 (59%) Total 88/243 (36%)131/232 (56%) Viral load 12 months 1 after starting 1st and 2nd line cART for those switching 2 to 2nd line ( N=300 children switched to 2 nd line after at least 12 months on 1 st line 3 )

14. Data on 1188 children who are alive and in active follow-up (1175 in CHIPS clinics and 13 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.

15. Demographics (N=1188) (Data provided by NSHPC) 611 (51%) are female 567 (48%) born UK/Ireland, 609 (51%) born abroad (place of birth not known for 12 children) Ethnicity: Diagnosis of maternal infection (N=1144 vertically infected): White 69(6%) Black African 945(80%) Black other 13(1%) Indian 14(1%) Mixed 117(10%) Other 13(1%) Not known 17(1%) Known after delivery949(83%) Known before delivery 152(13%) Not known43(4%)

16. 610 (51%) London 49 (4%) Scotland 445 (37%) Rest of England 65 (5%) Ireland 14 (1%) Wales Regional distribution of main follow-up clinic for 1188 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

17. Year of last follow-up (N=1188)

18. Clinical stage by age at last follow-up (N=1188) No. of children< 2 years2-4 years5-9 years10-14 years≥15 yearsTotal(%) Stage N/A 15(83%)40(69%)164(61%)288(54%)150(48%) 657(55%) Stage B 0(0%)4(7%)41(15%)121(23%)90(29%) 256(22%) Stage C 3(17%)14(24%)62(23%)121(23%)75(24%) 275(23%) Total 18(100%)58(100%)267(100%)530(100%)315(100%)1188(100%)

19. Antiretroviral drug experience N=1102 children with follow-up since January 2010 No. of children < 2 years2-4 years5-9 years10-14 years≥15 yearsTotal(%) Naive1(6%)7(13%)54(23%)66(13%)23(8%) 151(14%) 1-4 drugs13(81%)36(65%)130(54%)221(44%)94(33%) 494(45%) 5-7 drugs2(13%)12(22%)51(21%)160(32%)95(33%) 320(29%) 8+ drugs0(0%)0 4(2%)57(11%)76(26%) 137(12%) Total16(100%)55(100%)239(100%)504(100%)288(100%)1102(100%)

20. ART at last follow-up N=877 children with follow-up since Jan 2010 were on treatment 17 on mono, 42 on dual, 753 on 3-drug, 60 on 4-drug and 5 on 5(+)-drug therapy

21. Most recent CD4% (N=1072) Children followed up since January 2010 (missing for 30 children) No. of children 0-10%11-20%21-30%>30% Naïve 1(3%)35(23%)57(16%)49(13%) On mono 3(9%)6(4%)3(1%)5 On dual 4(12%)5(3%)14(4%)17(3%) On initial cART 5(15%)35(23%)138(39%)266(50%) On subseq cART 15(45%)46(30%)112(32%)184(35%) Off ART 5(15%)28(18%)30(8%)9(2%) Total 33(100%)155(100%)354(100%)530(100%)

22. Most recent CD4 count (N=1106) Children ≥ 5 years old followed up since Jan 2010 (missing for 19 children) No. of children 0-200201-350351-500501-1000>1000 Naïve 0(0%)8(10%)42(22%)74(15%)14(7%) On mono 4(9%)4(5%)2(1%)6 1 On dual 3(7%)4(5%)7(4%)20(4%)8 On initial cART 9(21%)24(30%)53(28%)201(40%)106(54%) On subseq cART 23(53%)25(31%)61(32%)174(35%)64(33%) Off ART 4(9%)15(19%)24(13%)24(5%)2(1%) Total 43(100%)80(100%)189(100%)499(100%)195(100%)

23. No. of children ≤50c/ml (or ≤lower assay limit**) >50c/ml (or>lower assay limit) – 100,000c/ml >100,000c/ml Naïve 5(1%)126(32%)12(33%) On mono 7(1%)9(2%)0(0%) On dual 22(3%)20(5%)0(0%) On initial cART 360(56%)78(20%)7(19%) On subseq cART 249(38%)99(25%)9 Off ART 5(1%)58(15%)8(22%) Total 648(100%)390(100%)36(100%) Most recent viral load (N=1074) Children followed up since January 2010 (missing for 28 children) **5/648 (1%) of undetectable results had a lower limit of detection >50 but ≤400c/ml and are included here.

24. Involvement in PENTA trials KONCERT (PENTA 18) and BREATHER (PENTA 16) enrolment is ongoing in 2012. Please contact penta@ctu.mrc.ac.uk for further details of these trials)penta@ctu.mrc.ac.uk KONCERTBREATHER London – 10Oxford – 2London – 8 Birmingham – 1Liverpool – 1 Bristol – 2 Bristol – 1 Ireland – 1 Ireland – 1 Nottingham – 2 Recent PENTA publications: Lewis J, Walker AS, Castro H, De Rossi A, Gibb DM, Giaquinto C, Klein N, Callard R. Age and CD4 Count at Initiation of Antiretroviral Therapy in HIV-InfectedChildren: Effects on Long-term T-Cell Reconstitution. J Infect Dis. 2011 Dec 28. Compagnucci A. on behalf of the PENTA Steering Committee. Long Term consequences of planned treatment interruptions in HIV infected children: Results from the TICCH (Treatment Interruption in Children with Chronic HIV-Infection )/PENTA 11 trial. 3rd HIV Paediatric Workshop Rome 15-16 July 2011. Ramos J., Melvin D, Medin G, Compagnucci A, Bleier J, Boscolo V, Barclay L, Ory S, Giaquinto C, Gibb D. on behalf of the PENTA Steering Committee. Neurocognitive and Quality of Life Outcomes in Children after Planned Treatment Interruptions: the randomized PENTA 11 trial. 19th Conference on Retroviruses and Opportunistic Infections, San Francisco, 5-8 March 2012, Poster Mbisa JL, Hue S, Buckton AJ, Myers RE, Duiculescu D, Ene L, Oprea C, Tardei G, Rugina S, Mardarescu M, Floch C, Notheis G, Zoehrer B, Cane PA, Pillay D. Phylodynamic and Phylogeographic Patterns of the HIV-1 Subtype F1 Parenteral Epidemic in Romania. AIDS Res Hum Retroviruses 2012 Jan 18.

25. Recent CHIPS-related publications (based either wholly or partly on CHIPS data) Donegan KL, Walker AS, Dunn D, Judd A, Pillay D, Menson E, Lyall H, Tudor-Williams G, Gibb DM on behalf of the Collaborative HIV Paediatric Study and the UK HIV Drug Resistance Database. The prevelence of Darunavir associated mutations in HIV-1 infected children in the UK. Antiviral Therapy - in press. Judd A, Duong T, Ene L, Galli L, Goetghebuer T, Noguera-Julian A, Ramos JT, Tookey P, Naver L, Thorne C, Giaquinto C on behalf of the European Pregnancy and Paediatric HIV Cohort Collaboration (EPPICC) in EuroCoord. Safety of fosamprenavir and darunavir in HIV-1 infected children in the European Union: an ongoing post-marketing surveillance study. ESPID – poster presentation; IWHOD – poster presentation. The European Pregnancy and Paediatric HIV Cohort Collaboration (EPPICC). Early antiretroviral therapy in HIV-1 infected infants in Europe, 1996-2008: treatment response and duration of first-line regimens. AIDS 2011; 25(18): 2279- 2287. The Pursuing Later Treatment Options II (PLATO II) Project Team for the Collaboration of Observational HIV Epidemiological Research Europe (COHERE). Risk of triple class virologic failure in HIV-infected children. The Lancet 2011 May 7; 377(9777): 1580-1587.

26. 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