1. CONCLUSIONS  Mortality and hospital admission rates continued to decline since the introduction of HAART in 1997  Viral load suppression 12 months after HAART initiation improved over time  Results suggest a better immunological response in girls, but require further investigation  Low rates of switching to second line therapy were observed  Increased triple class exposure complicates longer term clinical management  Provision of transitional services and continued monitoring will be essential as the cohort ages into adolescence and adulthood BACKGROUND The National Study of HIV in Pregnancy and Childhood (NSHPC) is a voluntary confidential reporting scheme for HIV/AIDS diagnoses in pregnant women and children, covering the whole of the UK and Ireland. The Collaborative HIV Paediatric Study (CHIPS) is a multicentre cohort study of HIV infected children under care in the UK and Ireland since 1996. 39 hospitals in the UK and Ireland currently collaborate in the CHIPS study, accounting for  90% of all children currently in the NSHPC. CHIPS is being extended to the whole of the UK and Ireland during 2006/7. COLLABORATORS We thank staff and families from the hospitals collaborating in CHIPS/NSHPC, as well as the UK Department of Health, Bristol-Myers Squibb, Boehringer-Ingelheim, GlaxoSmithKline, Roche, Abbott and Gilead for financial support. CHIPS Steering Committee members: Karina Butler, Sheila Donaghy, David Dunn, Trinh Duong, Di Gibb, Ali Judd, Hermione Lyall, Janet Masters, Esse Menson, Vas Novelli, Catherine Peckham, Andrew Riordan, Mike Sharland, Pat Tookey, Gareth Tudor-Williams, Gillian Wait. SOCIODEMOGRAPHICS  50% female  72% black African, 13% white, 16% other  55% born in the UK and Ireland, 45% born abroad  Median age at presentation varied by country of birth: - constant for the UK and Ireland at ~0.5 years - increased from 2 years up to 1991 to 8 years in 2004/5 for those born abroad  13% identified prospectively from birth, 68% prior to an AIDS diagnosis, and 19% at AIDS diagnosis  94% vertically infected, 3% blood transfusion, 3% other RATES OF PROGRESSION TO AIDS AND DEATH  Rates (per 100 person years) have continued to decline since the introduction of HAART: YearAIDS/deaths (95%CI)Deaths (95%CI) -199613.4(11.4-15.6)8.3(6.9-9.8) 1997-95.7(4.3-7.5)1.9(1.2-2.8) 2000-23.2(2.3-4.3)0.9(0.6-1.5) 2003-52.7(1.9-3.6)0.6(0.3-1.1)  18 children died in 2003-5:  7 presented with AIDS and/or died within one month  Of the remaining 11: - only 3 were on HAART for 6+ months prior to death - primary cause of death was opportunistic infections (2), HIV encephalopathy (1), sepsis (1), lung disease (1), other (3), and not known (3) METHODS  Analyses relating to HAART exposure and response are confined to children in CHIPS only (n=1065). All other analyses include all diagnosed children (n=1439)  Our definition of “first line" 3 or 4 drug HAART allows for 1 or 2 drug substitutions (if not made for virological, immunological or clinical failure), and drug intensifications or reductions  Logistic regression was used to explore responses to HAART. All odds ratios (ORs) are adjusted for: age, CD4% and HIV-1 RNA at HAART initiation; sex; CDC B/C events prior to HAART; number of drugs in the initial HAART regimen; year started HAART; and timing of response measurements KEY PAPERS Gibb DM et al. Decline in mortality, AIDS, and hospital admissions in perinatally HIV-1 infected children in the United Kingdom and Ireland. BMJ 2003,327:1019. Walker AS et al. Response to highly active antiretroviral therapy varies with age: the UK and Ireland Collaborative HIV Paediatric Study. AIDS 2004,18:1915-1924. Menson EN et al. Systematic inaccurate prescribing of paediatric antiretroviral drugs - a good example of universal bad practice in medicines for children? BMJ - in press REGIONAL DISTRIBUTION OF CHILDREN  Most children are seen in London hospitals 5% Ireland 1% Wales 66% London 23% Rest of England 5% Scotland 0% N. Ireland 12 MONTH IMMUNOLOGICAL AND VIROLOGICAL RESPONSE TO HAART  76% suppressed viral load <400 copies/ml in 2003/5, compared to only 51% in 1997/9. *A cut off of <50 copies/ml could not be used due to some hospitals continuing to use the “<400” cut off in recent years. † Multivariable. ‡ Baseline=1997/9 PRIOR DRUG CLASS EXPOSURE OVER TIME  At last follow up, 27% of 5-9, 33% of 10-14, and 38% of 15+ year olds had been exposed to all three main classes of HAART HOW THE NSHPC & CHIPS WORK TOGETHER Children diagnosed with HIV are initially reported to the NSHPC. Once the infection is confirmed, the NSHPC informs CHIPS, which sends out detailed annual follow up questionnaires if the child is seen in a hospital collaborating in CHIPS. For hospitals not in CHIPS, a brief annual follow up form is sent out by the NSHPC. Data are shared between the studies in order to undertake joint analyses. AIM The aim of this analysis was to describe changes over time in demographics, morbidity and mortality, and exposure and response to HAART, in HIV infected children in the UK and Ireland between 1996 and 2005. AGE GROUP BY CALENDAR YEAR OF REPORT  Median age of the cohort increasing year on year  13%  10 years in 1996 compared to 46% in 2005 CD4% increase of >10%HIV-1 RNA <400 copies/ml* OR † 95% CIpOR † 95% CIp Age at HAARTper year0.850.78-0.92<0.0011.030.96-1.100.469 CD4% at HAARTper 5%0.550.47-0.64<0.0011.050.93-1.180.428 Sexfemale1.681.01-2.810.0440.970.60-1.570.905 Calendar year at HAART ‡ 2000/20.920.50-1.702.271.30-3.96 2003/51.120.59-2.120.8332.991.60-5.590.001 HAART EXPOSURE AND SWITCHING  595 children in CHIPS started a HAART regimen since 1997 and were ART naïve at the start of HAART  93% remained on first line HAART at 12 months, 86% at 24 months, and 79% at 36 months  Median time to switching to second line was 7.2 years  Whilst the proportion of child time spent on three drug ART was stable at ~62% from 2000 onwards, the proportion of time spent off all ART, having previously taken it, increased from 3% in 1997/9 to 9% in 2003/5. CONTACT FOR FURTHER INFORMATION Ali Judd MRC Clinical Trials Unit 222 Euston Road +44 20 7670 4830 London NW1 2DA a.judd@ctu.mrc.ac.uk www.chipscohort.ac.uk Older and wiser: continued improvements in clinical outcome and highly active antiretroviral therapy (HAART) response in HIV-infected children in the UK and Ireland, 1996-2005 A Judd 1, T Duong 1, K Lee 1, AS Walker 1, PA Tookey 2, M Sharland 3, A Riordan 4, H Lyall 5, J Masters 2, E Menson 3, G Tudor-Williams 5, K Butler 6, S Donaghy 3, V Novelli 7, C Peckham 2, DM Gibb 1 for the Collaborative HIV Paediatric Study and the National Study of HIV in Pregnancy and Childhood 1 MRC CTU, London; 2 Institute of Child Health, London; 3 St George’s Hospital, London; 4 Royal Liverpool Children’s Hospital, Liverpool; 5 St Mary’s Hospital, London; 6 Our Lady’s Hospital for Sick Children, Dublin; 7 Great Ormond Street Hospital, London.