Advancements in Pediatric HIV Treatment: A Decade of Progress in the UK & Ireland (1996-2005)

1. 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 Collaborative HIV Paediatric Study (CHIPS) A Judd, T Duong, KJ Lee, AS Walker, PA Tookey, M Sharland,A Riordan, H Lyall, J Masters, E Menson, G Tudor-Williams,K Butler, S Donaghy, V Novelli, C Peckham, DM Gibb

2. 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 in NSHPC are also in CHIPS • detailed annual follow up questionnaires • For those not in CHIPS, NSHPC collects limited annual follow up data

3. Aim • Describe changes over time in demographics, morbidity and mortality, and exposure and response to HAART • HIV infected children in the UK & Ireland • 1996 - 2005

4. Methods • HAART exposure and response data are for CHIPS children only (n=1065). All other analyses include all diagnosed children (n=1439) • Logistic regression to explore 12 month viral load and CD4% responses to HAART in ART naïve children

5. Regional distribution of children 5% Scotland <1% N. Ireland 23% Rest of England 5% Ireland 1% Wales 66% London

6. Sociodemographics Sex:How child was identified: Female 50% Prospectively 13% Before AIDS 68% Ethnicity: AIDS diagnosis 19% Black African 72% White 13% Source of infection: Other 16% Vertical 94% Blood transfusion 3% % born abroad: Other 3% Early 1990s ~30% 2000+ ~65%

7. Age group & sample size by year N: 386 425 505 561 647 745 837 954 1006 802* * 2005 = provisional data, subject to reporting delay

8. HAART exposure and switching • 595 children started a HAART regimen since 1997 and were ART naïve before HAART • median age = 5 years (IQR 2-9) • Median time to switching to 2nd line =7.2 yrs • [switching = 2 drugs substituted because of failure (CD4/ VL/ clinical/ resistance), or all drugs changed] • At last follow up: • 33% of 10-14 year olds and 41% aged 15 were triple class exposed • 9% of 10-14 year olds and 14% aged 15 were off all ART, after previously receiving HAART

9. VL decrease <400 c/ml at 12 months Variable % Odds ratio(95%CI) Year started HAART 1997/9 (baseline) 51% 1.00 2000/2 70% 2.27 (1.30-3.96) 2003/5 76% 2.99 (1.60-5.59) • No effect of age, or viral load at HAART All 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

10. CD4% increase >10% at 12 months Variable Odds ratio(95%CI) Age at HAART (per year) 0.85 (0.78-0.92) CD4% at HAART (per 5%) 0.55 (0.47-0.64) Sex Male (baseline) 1.00 Female 1.68 (1.01-2.81) • No effect of calendar year All 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

11. Rates of progression to AIDS/ death

12. Deaths in 2003/5 • 18 children died between 2003/5. Of these: • 7 presented with AIDS/ 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), gastrointestinal bleeding (1), chickenpox/ cardiovascular (1), neurocysticercosis • cause of 3 deaths unknown: • 1 was diagnosed at 4 months & died 6 weeks later; 2 were diagnosed at birth but subsequently returned to Africa and died there

13. Conclusions • Mortality and rates of progression to AIDS have continued to decline since HAART • Viral load suppression 12 months after HAART initiation improved with time • Low rates of switching to 2nd line therapy • Increased triple class exposure complicates clinical management • Provision of transitional services and continued monitoring essential as the cohort ages into adolescence and adulthood

14. 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 • www.chipscohort.ac.uk