1. Morbidity, mortality, and response to treatment in HIV-infected children in the UK & Ireland 1996-2006: a prospective cohort study Katja Doerholt, A Judd, P Tookey, M Sharland, A Riordan, E Menson, V Novelli, EGH Lyall, J Masters, G Tudor-Williams, T Duong, DM Gibb, on behalf of the Collaborative HIV Paediatric Study (CHIPS) and the National Study of HIV in Pregnancy and Childhood (NSHPC)

2. Aims Demographic data Antiretroviral therapy use Predictors of response to treatment Mortality & morbidity

3. Regional distribution of children 5% Ireland 1% Wales 65% London 24% Rest of England 4% Scotland <1% N. Ireland N=1441 National data from NSHPC Newly diagnosed 1994/6 81% follow up in London 2003/6 50% follow up in London

4. Age group by year of follow up N: 363 403 481 535 616 712 795 911 992 1002

5. Highly active antiretroviral therapy (HAART) exposure (N=1133 in CHIPS) 72% of children received HAART at some point 24% of children had never received ART 4% had taken only mono or dual therapy At last follow up: –32% of 10-14 year olds and 38% aged  15 taking HAART were triple class exposed –9% of 10-14 year olds and 13% aged  15 were off all HAART, after having previously received it

6. Predictors for response to HAART HIV-1 RNA at 12 monthsCD4% at 12 months Decrease to <400 c/mlAbsolute increase >10% n=375n=374 Adj ORp p Age started HAARTper year1.040.20.85<0.01 CD4% at HAARTper 5%1.030.60.56<0.01 HIV-1 RNA at HAARTper 1 log 10 c/ml0.930.71.280.2 B/C events < HAART*None1.00 B or C event0.880.60.960.9 Number of drugs in initial regimen31.00 42.140.061.230.6 Year started HAART1997-19991.00 2000-20022.06 0.98 2003-20063.45<0.011.160.8

7. Hospital admission, AIDS & mortality rates Up to

8. Morbidity in the era of HAART 49 children had 62 AIDS events reported since 2004

9. Mortality in the era of HAART Death ≥ 2004Death in <2 years N=4 Death ≥ 2 years N=8 Born in UK 41 Clinical presentation 3 presented with AIDS or/& died within 3 months of presentation 4 presented with AIDS or/& died within 3 months of presentation Primary cause of death Treatment naïve – PCP (1) – Septicaemia (1) --------------------- Died on HAART – CMV (1) – Cerebral haemorrhage (1) Treatment naïve – Chickenpox (1) – Septicaemia (1) ---------------------- Died on HAART – NHL (2) – Pneumonia (1) – MAI (1) – Septicaemia (1) – unknown (1)

10. Conclusions Continued increase of the age of the cohort emphasize the need for transitional services Dispersal highlights the importance of national networks AIDS/ mortality rates continue to decline Recent AIDS events or deaths are mainly due to late presentation Improved virological response to HAART over time Complex long term clinical management

11. Acknowledgements Thanks to everyone providing data to the NSHPC and CHIPS !! Republic of Ireland: Our Lady's Children’s Hospital Crumlin, Dublin: K Butler, A Walsh. UK: Birmingham Heartlands Hospital, Birmingham: Y Heath, J Sills; Blackpool Victoria Hospital, Blackpool: N Laycock; Bristol Royal Hospital for Children, Bristol: A Finn, A Foot, L Hutchison; Central Middlesex Hospital, London: M Le Provost, A Williams; Chase Farm Hospital, Middlesex; Chelsea and Westminster Hospital, London: D Hamadache, EGH Lyall, P Seery; Ealing Hospital, Middlesex: V Shah, K Sloper; Glasgow Royal Hospital for Sick Children, Glasgow: C Doherty, R Hague; Great Ormond St Hospital for Children, London: M Clapson, S Fasolo, J Flynn, DM Gibb, N Klein, K Moshal, V Novelli, D Shingadia; Hillingdon Hospital, London; Homerton University Hospital, London: D Gurtin; John Radcliffe Hospital, Oxford: A Pollard, S Segal; King's College Hospital, London: C Ball, S Hawkins, D Nayagam; Leeds General Infirmary, Leeds: P Chetcuti; Leicester Royal Infirmary, Leicester: M Green, J Houghton; Luton and Dunstable Hospital, Luton: M Connan, M Eisenhut; Mayday University Hospital, Croydon: J Baverstock, J Handforth; Milton Keynes General Hospital, Milton Keynes: PK Roy; Newcastle General Hospital, Newcastle: J Clarke, K Doerholt, C Waruiru; Newham General Hospital, London: C Donoghue, E Cooper, S Liebeschuetz, S Wong; Ninewells Hospital and Medical School, Dundee: T Lornie; North Manchester General Hospital, Manchester: C Murphy, T Tan; North Middlesex Hospital, London: J Daniels, EGH Lyall, B Sampson-Davis; Northampton General Hospital, Northampton: F Thompson; Northwick Park Hospital, Middlesex; M Le Provost, A Williams; Nottingham City Hospital, Nottingham: D Curnock, A Smyth, M Yanney; Queen Elizabeth Hospital, Woolwich: W Faulknall, S Mitchell; Royal Belfast Hospital for Sick Children, Belfast: S Christie; Royal Edinburgh Hospital for Sick Children, Edinburgh: J Mok; Royal Free Hospital, London: S McKenna, V Van Someren; Royal Liverpool Children’s Hospital, Liverpool: C Benson, A Riordan; Royal London Hospital, London: B Ramaboea, A Riddell; Royal Preston Hospital, Preston: AN Campbell; Sheffield Children's Hospital, Sheffield: J Hobbs, F Shackley; St George's Hospital, London: R Chakraborty, S Donaghy, R Fluke, M Sharland, S Storey, C Wells; St Mary's Hospital, London: D Hamadache, C Hanley, EGH Lyall, G Tudor-Williams, C Walsh, S Walters; St Thomas' Hospital, London: R Cross, G Du Mont, E Menson; University Hospital Lewisham, London: D Scott, J Stroobant; University Hospital of North Staffordshire, Stoke On Trent: P McMaster; University Hospital of Wales, Cardiff: B O' Hare; Wexham Park, Slough: R Jones; Whipps Cross Hospital, London: K Gardiner; Whittington Hospital, London. Funding: NSHPC is funded by the Health Protection Agency, and has also received support from the UK Department of Health and the Medical Research Council. CHIPS is funded by the Department of Health and in the past received additional support from Bristol-Myers Squibb, Boehringer Ingelheim, GlaxoSmithKline, Roche, Abbott, and Gilead. Committees and participants (in alphabetical order): CHIPS Steering Committee: K Butler, K Doerholt, S Donaghy, DT Dunn, T Duong, DM Gibb, A Judd, EGH Lyall, J Masters, E Menson, V Novelli, C Peckham, A Riordan, M Sharland, D Shingadia, PA Tookey, G Tudor-Williams, G Wait MRC Clinical Trials Unit: DT Dunn, T Duong, L Farrelly, DM Gibb, D Johnson, A Judd, G Wait, AS Walker National Study of HIV in Pregnancy & Childhood, Institute of Child Health: J Masters, C Peckham, PA Tookey