1. Exposure and response to highly active antiretroviral therapy (HAART) in ART naïve children in the UK and Ireland Judd A. 1, Lee K.J. 1, Duong T. 1, Walker A.S. 1, Butler K. 2, Donaghy S. 3, Dunn D.T. 1, Lyall H. 4, Masters J. 5, Menson E. 3, Novelli V. 6, Peckham C. 5, Riordan A. 7, Sharland M. 3, Tookey P. 5, Tudor-Williams G. 4, Gibb D.M. 1 on behalf of “CHIPS” 1 MRC Clinical Trials Unit, London, UK, 2 Our Lady's Hospital for Sick Children, Dublin, Ireland, 3 St George's Hospital, London, UK, 4 St Mary's Hospital, London, UK, 5 Institute for Child Health, London, UK, 6 Great Ormond Street Hospital for Sick Children, London, UK, 7 Royal Liverpool Children's Hospital, Liverpool, UK CONCLUSIONS  The median age of the cohort has increased year on year  AIDS progression and mortality rates continued to decline since the introduction of HAART in 1997  CD4% increases >10% were more likely in younger children and those with lower pre-HAART CD4%, as found in a previous analysis (Walker et al 2004)  Viral load suppression 12 months after HAART initiation improved with calendar year, but was not related to age at HAART, unlike previously  Low rates of switching to second line therapy were observed  The proportion of child time spent off all ART after having previously received it increased with calendar year  The proportion of triple class exposed children has been relatively stable over the last five years, reflecting the durability of first and second line HAART in this cohort  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 active reporting scheme for pregnancies in HIV-infected women, babies born to HIV-infected women, and children with HIV infection, 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. 41 hospitals in the UK and Ireland currently collaborate in the CHIPS study, accounting for  90% of all children reported to the NSHPC in 2005. 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. CHIPS is funded by the UK Department of Health. Additional support was obtained from Bristol-Myers Squibb, Boehringer-Ingelheim, GlaxoSmithKline, Roche, Abbott and Gilead. CONTACT FOR FURTHER INFORMATION Ali Judd +44 20 7670 4830 MRC Clinical Trials Unit a.judd@ctu.mrc.ac.uk 222 Euston Road London NW1 2DA SOCIODEMOGRAPHICS (n=1522)  50% female  71% black African, 14% white, 15% other  51% born in the UK and Ireland, 49% born abroad  Median age at presentation varied by country of birth: - constant at ~0.5 years until 2001, then rose to one year in 2004/6, for those born in the UK and Ireland - increased yearly from 2 years before 1991 to 8 years in 2004/6 for those born abroad  12% identified prospectively from birth, 69% prior to an AIDS diagnosis, and 19% at AIDS diagnosis  94% vertically infected, 3% blood transfusion, 3% other METHODS  Data are for reports received to end of March 2006  Analyses are for all diagnosed children (n=1522), except HAART exposure & response which are for CHIPS children only (n=1169)  Crude rates of progression to AIDS and death per 100 person years at risk were calculated by year  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 UK and Ireland. BMJ 2003,327:1019. Walker AS et al. Response to HAART varies with age: the UK and Ireland Collaborative HIV Paediatric Study. AIDS 2004,18:1915-1924. Doerholt K et al. Outcomes for HIV-1-infected infants in the UK and Republic of Ireland in the era of effective antiretroviral therapy. PIDJ 2006; 25: 420-426. Menson EN et al. Underdosing of antiretrovirals in UK and Irish children with HIV as an example of problems in prescribing medicines to children, 1997- 2005: cohort study. BMJ 2006,332:1183-1187 REGIONAL DISTRIBUTION (n=1522) 6% Ireland 1% Wales 64% London 24% Rest of England 4% Scotland 0% N. Ireland 12 MONTH IMMUNOLOGICAL AND VIROLOGICAL RESPONSE TO HAART (n=666 starting HAART naive)  78% suppressed viral load <400 copies/ml in 2003/5, compared to only 52% 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 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: characteristics of the CHIPS cohort; HAART use in previously untreated children; and the effect of age, sex, and CD4%, HIV-1 RNA and year at HAART initiation, on response to first line treatment at 12 months AGE GROUP BY YEAR OF REPORT (n=1522)  Median age increased year on year  44%  10 years in 2005 compared to 11% in 1996 CD4% increase of >10%HIV-1 RNA <400 copies/ml* OR † 95% CIpOR † 95% CIp Age at HAARTper year0.850.80-0.92<0.0011.030.97-1.100.339 CD4% at HAARTper 5%0.560.48-0.64<0.0011.030.91-1.150.659 Sexfemale1.560.97-2.510.0671.120.71-1.760.638 Calendar year at HAART ‡ 2000/21.070.59-1.941.981.16-3.39 2003/51.150.64-2.090.8973.511.94-6.320.001 HAART EXPOSURE AND SWITCHING (n=1169)  666 children in CHIPS started a HAART regimen since 1997 and were ART naïve at the start of HAART  Median age at HAART was 4.8 years (IQR1.5-8.9)  93% remained on first line* HAART after 12 months, 86% after 24 months, and 79% after 36 months (*in this analysis, “first line" 3-4 drug HAART allows for 1-2 drug substitutions (if not made for viral load, CD4 or clinical failure), & drug intensifications/ reductions)  Median time to switching to second line was 7 years  Whilst the proportion of child time spent on 3 or 4 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. RATES OF PROGRESSION TO AIDS AND DEATH (n=1522)  Rates (per 100 person years) have continued to decline since the introduction of HAART: YearAIDS/deaths (95%CI)Deaths (95%CI)  199613.3 (11.3-15.5)8.2(6.9-9.8) 1997-95.7(4.3-7.4)1.9(1.2-2.8) 2000-23.0(2.2-4.1)0.9(0.6-1.5) 2003-52.5(1.8-3.4)0.6(0.3-1.0)  20 children died in 2003-5:  9 presented with AIDS and/or died within one month  Of the remaining 11: - only 4 were on HAART for 6+ months prior to death - primary cause of death: OI (2), HIV encephalopathy (1), sepsis (1), lung disease (1), other (4), unknown (2) Year n 363 403 481 535 617 713 796 911 989 987 DRUG CLASS EXPOSURE OVER TIME (n=1169)  At last follow up, 27% of 5-9, 33% of 10-14, and 36% of 15+ year olds had been exposed to all three main classes of HAART Year n 23 127 187 250 298 359 449 504 443 Poster number THPE0106 www.chipscohort.ac.uk