1. Patients with perinatal HIV transitioning to adult care
in the UK
Intira Jeannie Collins1, Francesca Parrott1, Caroline Sabin2, Teresa Hill2, Sophie Jose2 and Ali Judd1 on behalf of the Collaborative HIV Paediatric Study (CHIPS) Steering Committee and the UK Collaborative HIV Cohort Study (UK CHIC)
P_82
1MRC Clinical Trials Unit at University College London, UK; 2 Research Department of Infection and Population Health, University College London, UK
Introduction
Due to improved survival for patients with perinatal HIV, adolescents are now transitioning from paediatric to adult care.
There are few published data on clinical outcomes post-transfer. We used linked data from CHIPS and UK CHIC cohorts to describe mortality, antiretroviral treatment (ART), CD4 and viral load status pre- and post-transfer and to model CD4 change over the transition period.
Methods
The Collaborative HIV Paediatric Study (CHIPS): a multi-centre national cohort study of all children aged<16 years at diagnosis of HIV in UK/Ireland.
A mixed effects model was fitted (allowing for multiple measures per person) to predict CD4 over time, adjusting for:
Demographic characteristics (sex, ethnicity, born abroad)
The UK Collaborative HIV Cohort Study (UK CHIC): a multi-centre cohort of HIV positive adults aged ≥16 years attending a collaborating adult clinic, represents approx. one-third of the national adult HIV population.
Nadir CD4 cell count in paediatric care
Age at transfer out of paediatric care, change of hospital at transfer
Viral load <400c/mL (time-updated) within 6 months of the CD4 measurement
Patients followed in CHIPS and aged ≥13 years by end of 2013 were matched with adults in UK CHIC.
Time before/after transfer (modelled as a linear spline with one knot at transfer, time=0)
Key outcomes in paediatric vs adult care were compared: (i) Proportion on ART; (ii) median CD4 count (iii) proportion with CD4<200 cells/mm3 in 24 months pre/post transfer and (iv) proportion with two consecutive VL>400 copies/mL while on ART for ≥6 months in 24 months pre/post transfer
A priori interactions included were time from transfer with both age at transfer and change of hospital. Interactions of time with other variables were included if p<0.05.
Results
Of 1215 CHPS patients aged≥13 years, 271 (22%) were matched to UK CHIC, of whom 229 (85%) were documented in CHIPS as transferred to adult care, 25 (9.2%) were lost to follow-up in paediatric care and 17 (6.3%) were reported as still in paediatric care (due to reporting delay or being in the transition process).
Median age of transfer out of paediatric care was 17 years and median duration of adult care follow up was 2.9 years (Table 1).
For the key outcomes in paediatric vs adult care (Table 2):
the proportion on ART increased from 74% to 84%, respectively
median CD4 count was similar
among those on ART, the proportion with VL>400 was similar.
Predictors of CD4 over time
CD4 was generally stable pre-transfer and declined after transfer to adult care (p=0.017) (Table 3).
Pre-transfer CD4 slope was worse among females (vs males) and better for those with viral load suppression (Figure). There was a small but significant effect of worse slope with higher nadir CD4.
The CD4 slope post transfer was better among females, and with some evidence of improved slope with older age at transfer (p=0.051).
There was no effect of ethnicity or being born abroad on CD4 pre- or post-transfer. Change of hospitals at transfer had no effect on CD4 post-transfer.
Table 1: Patient characteristics, N=271
Characteristic
n (%) / median [IQR]
Female
146 (53%)
Perinatal HIV infection
237 (96%)
Black ethnicity
213 (80%)
Born abroad
163 (61%)
Ever AIDS diagnosis*
86 (32%)
Age at transfer out of paediatric care (years)
17 [16,18]
Age at last follow up in adult care (years)
20 [19,23]
Duration of paediatric care follow up (years)
11.8 [6.6,15.5]
Duration of adult care follow up (years)
2.9 [1.5,5.9]
Gap between paediatric & adult care (months)**
2.4 [1.0,4.4]
Duration of total follow up (years)
15.4 [10.6,19.3]
Note: *77 had first AIDS event in paediatric care. **17 had gaps between care >12 months
Table 2: Comparing key outcomes in paediatric and adult care
Outcome
Paediatric care
Adult care
p-value
n (%) / median [IQR]
On ART at last follow up, N=271
200 (74%)
228 (84%)
0.001
Median CD4 count in 12 months pre/post transfer, N=189
456 [286,660]
450 [271,669]
0.37
CD4<200 at least once in 24 months pre/post transfer, N=195
61 (31%)
76 (39%)
0.01
Two consecutive VL>400 for those on ART for at least 6 months in 24 months pre/post transfer, N=181
91 (50%)
1.00
Table 3: Predictors of CD4 over time pre and post transfer, N=262
Predictors
Coefficient
95% CI
P-value
Main effects
Time before transition (per 1 year closer to transfer)
0.3
-8.9 , 9.6
0.94
Time after transition (per 1 year after transfer)
-91.4
, -16.2
0.017
Female
-75.8
, -29.4
0.001
Black ethnicity
-26.5
-81.8 , 28.9
0.35
Born abroad
-12.0
-57.4 , 33.5
0.61
Nadir CD4 cell count (per 10 unit increase)
6.5
5.0 , 8.0
<0.001
Viral suppression (time-updated)*
Non-suppressed
Suppressed <400 cps/mL
Missing
Ref
165.8
9.0
153.2 , 178.4
-56.3 , 74.3
0.79
Interactions with time before transition
-15.6
-25.5 , -5.7
0.002
Nadir CD4 cell count (per 10 unit increase)
-0.5
-0.74 , -0.2
6.0
-17.2
2.4 , 9.7
-32.1 , -2.2
0.024
Interactions with time after transition
21.7
10.0 , 33.5
Age at transfer out of paediatric care
4.2
-0.0 , 8.5
0.051
Changed hospital at transfer
8.0
-2.2 , 18.3
0.13
Figure: The effect of sex and time updated viral suppression on CD4 slopes over time for an example patient with the following characteristics: Black ethnicity, born in the UK, nadir CD4 of 207 cells/mm3, transferred to adult care at 17.5 yrs (sample means), no hospital change at transfer
Conclusion
This is the first analysis to match perinatally HIV infected adolescents followed in the CHIPS national cohort with the UK CHIC adult cohort, with follow-up data post-transfer to adult care.
The proportion of patients on ART increased after transfer, although there was no change in the median CD4 count or the proportion with confirmed viremia on ART.
After adjustment for other variables, CD4 appears to be relatively stable prior to transfer and decreases post-transfer.
Some characteristics were protective of CD4 decline: females, older age at transfer and being virologically suppressed were associated with better CD4 slopes post transfer.
Collaborative HIV Paediatric Study (CHIPS): CHIPS is funded by the NHS (London Specialised Commissioning Group) and has received additional support from Bristol-Myers Squibb, Boehringer Ingelheim, GlaxoSmithKline, Roche, Abbott, and Gilead Sciences. Participate hospitals: Republic of Ireland: Our Lady's Children’s Hospital Crumlin, Dublin: K Butler, A Walsh. UK: Birmingham Heartlands Hospital, Birmingham: S Scott, Y Vaughan, S Welch; Blackpool Victoria Hospital, Blackpool: N Laycock; Bristol Royal Hospital for Children, Bristol: J Bernatoniene, A Finn, L Hutchison; Calderdale Royal Hospital, Halifax: G Sharpe; Central Middlesex Hospital, London: A Williams; Chelsea and Westminster Hospital, London: EGH Lyall, P Seery; Coventry & Warwickshire University Hospital, Coventry: P Lewis, K Miles; Derbyshire Children’s Hospital, Derby: B Subramaniam; Derriford Hospital, Plymouth: L Hutchinson, P Ward; Ealing Hospital, Middlesex: K Sloper; Eastbourne District General Hospital, Eastbourne: G Gopal; Glasgow Royal Hospital for Sick Children, Glasgow: C Doherty, R Hague, V Price; Great Ormond St Hospital for Children, London: H Bundy, M Clapson, J Flynn, DM Gibb, N Klein, V Novelli, D Shingadia; Halliwell Children’s Centre, Bolton: P Ainsley-Walker; Harrogate District Hospital, Harrogate: P Tovey; Homerton University Hospital, London: D Gurtin; Huddersfield Royal Infirmary, Huddersfield: JP Garside; James Cook Hospital, Middlesbrough: A Fall; John Radcliffe Hospital, Oxford: D Porter, S Segal; King's College Hospital, London: C Ball, S Hawkins; Leeds General Infirmary, Leeds: P Chetcuti, M Dowie; Leicester Royal Infirmary, Leicester: S Bandi, A McCabe; Luton and Dunstable Hospital, Luton: M Eisenhut; Mayday University Hospital, Croydon: J Handforth; Milton Keynes General Hospital, Milton Keynes: PK Roy; Newcastle General Hospital, Newcastle: T Flood, A Pickering; Newham General Hospital, London: S Liebeschuetz; Norfolk & Norwich Hospital, Norwich: C Kavanagh; North Manchester General Hospital, Manchester: C Murphy, K Rowson, T Tan; North Middlesex Hospital, London: J Daniels, Y Lees; Northampton General Hospital, Northampton: E Kerr, F Thompson; Northwick Park Hospital Middlesex; M Le Provost, A Williams; Nottingham City Hospital, Nottingham: L Cliffe, A Smyth, S Stafford; Queen Alexandra Hospital, Portsmouth: A Freeman; Raigmore Hospital, Inverness: T Reddy; Royal Alexandra Hospital, Brighton: K Fidler; Royal Belfast Hospital for Sick Children, Belfast: S Christie; Royal Berkshire Hospital, Reading: A Gordon; Royal Children’s Hospital, Aberdeen: D Rogahn; Royal Cornwall Hospital, Truro: S Harris, L Hutchinson; Royal Devon and Exeter Hospital, Exeter: A Collinson, L Hutchinson; Royal Edinburgh Hospital for Sick Children, Edinburgh: L Jones, B Offerman; Royal Free Hospital, London: V Van Someren; Royal Liverpool Children’s Hospital, Liverpool: C Benson, A Riordan; Royal London Hospital, London: A Riddell; Royal Preston Hospital, Preston: R O’Connor; Salisbury District General Hospital, Salisbury: N Brown; Sheffield Children's Hospital, Sheffield: L Ibberson, F Shackley; Southampton General Hospital, Southampton: SN Faust, J Hancock; St George's Hospital, London: K Doerholt, S Donaghy, K Prime, M Sharland, S Storey; St Luke’s Hospital, Bradford: S Gorman; St Mary’s Hospital, London: EGH Lyall, C Monrose, P Seery, G Tudor-Williams, S Walters; St Thomas’ Hospital (Evelina Children’s Hospital), London: R Cross, E Menson; Torbay Hospital, Torquay: J Broomhall, L Hutchinson; University Hospital Lewisham, London: D Scott, J Stroobant; University Hospital of North Staffordshire, Stoke On Trent: A Bridgwood, P McMaster; University Hospital of Wales, Cardiff: J Evans, T Gardiner; Wexham Park, Slough: R Jones; Whipps Cross Hospital, London: K Gardiner; Steering Committee: Hermione Lyall, Karina Butler, Intira Jeannie Collins, Katja Doerholt, Caroline Foster, Di Gibb, Lynda Harper, Ali Judd, Nigel Klein, Esse Menson, Andrew Riordan, Delane Shingadia, Gareth Tudor-Williams, Pat Tookey, Steve Welch. MRC Clinical Trials Unit: IJ Collins, C Cook, DM Gibb, A Judd, L Harper, F Parrott, A Tostevin, D Dobson.
United Kingdom Collaborative HIV Cohort (UK CHIC): UK CHIC Steering Committee: Jonathan Ainsworth, Jane Anderson, Abdel Babiker, Valerie Delpech, David Dunn, Philippa Easterbrook, Martin Fisher, Brian Gazzard (Chair), Richard Gilson, Mark Gompels, Teresa Hill, Margaret Johnson, Clifford Leen, Fabiola Martin, Chloe Orkin, Andrew Phillips, Deenan Pillay, Kholoud Porter, Caroline Sabin, Achim Schwenk, John Walsh. Central co-ordination: Research Department of Infection & Population Health, UCL, London (T Hill, S Huntington, S Jose, A Phillips, C Sabin, A Thornton); Medical Research Council Clinical Trials Unit (MRC CTU), London (D Dunn, A Glabay). Participating centres: Barts and The London NHS Trust, London (C Orkin, J Lynch, J Hand, C de Souza); Brighton and Sussex University Hospitals NHS Trust (M Fisher, N Perry, S Tilbury, D Churchill); Chelsea and Westminster NHS Trust, London (B Gazzard, M Nelson, M Waxman, D Asboe, S Mandalia); Public Health England, London (V Delpech); Homerton University Hospital NHS Trust, London (J Anderson, S Munshi, D Awosika); King’s College Hospital, London (F Post, H Korat, C Taylor, Z Gleisner, F Ibrahim, L Campbell); UCL Medical School and The Mortimer Market Centre, London (R Gilson, N Brima, I Williams); North Bristol NHS Trust (M Gompels, S Allen); North Middlesex University Hospital NHS Trust, London (A Schwenk, J Ainsworth, C Wood, S Miller); Royal Free NHS Trust and Department of Infection & Population Health, UCL, London (M Johnson, M Youle, F Lampe, C Smith, A Phillips, R Tsintas, C Chaloner, S Hutchinson); Imperial College Healthcare NHS Trust, London (J Walsh, N Mackie, A Winston, J Weber, F Ramzan); The Lothian University Hospitals NHS Trust, Edinburgh (C Leen, A Wilson); University of Leicester NHS Trust (A Palfreeman, A Moore, L Fox); South Tees Hospitals NHS Foundation Trust (D Chadwick, K Baillie); Woolwich NHS Trust (S Kegg, P Main); Coventry NHS Trust (S Allan); St. George’s NHS Trust (P Hay, M Dhillon); York (F Martin, S Douglas); The Royal Wolverhampton Hospitals NHS Trust (A Tariq, H Spencer, R Jones); Chertsey, Ashford and St Peter’s Hospitals NHS Foundation Trust (J Pritchard, S Cumming, C Atkinson); UK CHIC is funded by the UK Medical Research Council (Grant numbers G , G , G and M004236). The views expressed in this poster are those of the researchers and not necessarily those of the Medical Research Council.
Acknowledgements