Characteristics and responses to ART in the CHIPS cohort, Katja Doerholt and Ali Judd on behalf of the Collaborative HIV Paediatric Study (CHIPS) Steering Committee and the National Study of HIV in Pregnancy & Childhood (NSHPC)

Introduction to CHIPS & NSHPC Surveillance of obstetric and paediatric HIV in the UK and Ireland is carried out through the National Study of HIV in Pregnancy and Childhood (NSHPC) CHIPS is a multicentre cohort study of HIV infected children under care in 39 hospitals in the UK & Ireland since 1996 –  90% children currently reported to the NSHPC are also in CHIPS

Regional distribution of children 5% Ireland 1% Wales 65% London 24% Rest of England 4% Scotland <1% N. Ireland N=1444 National data from NSHPC

Sociodemographics New presentations seen at London hospitals 1994/681% 2003/652% Born abroad: Early 1990s30% % How child was identified: Prospectively13% Before AIDS68% AIDS diagnosis19%

Age group by year of follow up N:

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 year olds and 38% aged  15 taking HAART were triple class exposed –9% of year olds and 13% aged  15 were off all HAART, after having previously received it

VL decrease <400 c/ml at 12 months Variable %Odds ratio(95%CI) Year started HAART 1997/9 (baseline)52% /269%2.1 ( ) 2003/578%3.5 ( ) No effect of age, or viral load at HAART 2003/6 60% of children with VL<50 c/ml

CD4% increase >10% at 12 months VariableOdds ratio(95%CI) Age at HAART (per year)0.8 ( ) CD4% at HAART (per 5%)0.6 ( ) No effect of calendar year

Hospital admission, AIDS & mortality rates

Deaths in children died aged <1 year: –all were born in the UK/Ireland –5 presented with AIDS &/or died within one month 11 children died aged >=1 year: –4 presented with AIDS &/or died within one month –5 started HAART before they died

Conclusions Continued increase in new presentations and age of the cohort Importance of transitional services from adolescence to adulthood Geographical dispersion highlights the importance of national networks AIDS/ mortality rates continue to decline Improved virological response to HAART Complex long term clinical management

Current ongoing projects Roll out of CHIPS to all centres caring for HIV infected children in the UK & Ireland, in line with CHINN recommendations. Piloting of eCHIPS (electronic transfer of CHIPS data) is progressing. CHIPS is part of several meta analysis –HPPMCS: Short term risk of disease progression –COHERE: Effect of age on ART response –European Infant Collaboration: Early vs deferred ART in this infant cohort

Current ongoing projects Audit to evaluate the association between renal impairment and Tenofovir prescribing in CHIPS - Collaboration with 7 centres, Dave Cliff and Andrew Riordan with a grant from Gilead Sciences Several analysis are ongoing –Resistance testing (Collaboration with clinicians, virologist and statisticians) –Lipid abnormalities and ART exposure (GOS, St. Mary’s & UCL) –Description of adolescence (in collaboration with St. Mary’s) –Blipping and switching (Kate Lee)

Acknowledgements We thank: –staff and families from the hospitals collaborating in CHIPS, and Gill Wait, CHIPS Data Manager –all paediatricians and other health professionals reporting to the NSHPC, and the British Paediatric Surveillance Unit of the Royal College of Paediatrics and Child Health –UK Department of Health, HPA, Bristol-Myers Squibb, Boehringer-Ingelheim, GlaxoSmithKline, Roche, Abbott and Gilead for financial support

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