Switch to second-line therapy in the CHIPS cohort

1
Switch to second-line therapy in the CHIPS cohort

• Dr Kate Lee
• MRC Clinical Trials Unit
• On behalf of the Collaborative HIV Paediatric
  Study (CHIPS) Steering Committee

2
Aims

• Describe characteristics of switch to second-line
  therapy
• Investigate predictors of switch
• Explore CD4 and viral load at switch
• Assess timing of switch with respect to viral
  load thresholds

3
Methods

• Children starting HAART naïve
• Switch defined as
• Switching 3 drugs
• Switching 2 drugs with reason recorded as
  failure
• with VLgt50

4
Methods (contd)

• Median time to switch in children initiating
  HAART naive Kaplan-Meier
• Predictors of switch Cox model
• Sex
• Characteristics at HAART initiation
• Ever achieved suppression lt400 copies/ml
• Comparison of timing of switch with reaching
  viral load thresholds

5
Population (595 children)
1.00
Ever suppressed lt400c/ml
0.75
Overall median time to switch 7.2 years
Never suppressed lt400c/ml
0.50
0.25
0.00
0
1
2
3
4
5
6
7
8
Time (years)

• Children switching 132
• Median (range) follow-up 3.1 yrs (0-8.2 yrs)
• Median age at HAART initiation 5.6 (0-18)

6
Independent predictors of earlier switch

• Failure to ever achieve suppression lt400
  copies/ml
• HR 7.5 5.0-11.3 vs achieving suppression
  plt0.0001
• Older at HAART initiation
• HR 1.1 1.0-1.1 p0.03 per year older
• Later calendar year at HAART initiation
• HR 2.1 1.1-4.0 for 2002-05 vs 1997-99
  p0.03
• No independent effects of sex or age, CD4, HIV-1
  RNA or prior CDC B/C events at HAART initiation

7
At switch (median, range)

• Age 8.3 years (0.6-19.6)
• CD4 485 cells/mm3 (3-3592)
• 20 (0-47)
• Viral load 27,835 c/ml (50-1348000)

8
CD4 and Viral load at switch
50
40
30
CD4 at switch
20
10
0
50
100
1000
30000
100000
300000
1000000
Viral load at switch
Ever suppressed lt400
Never suppressed lt400
9
Compared to viral load thresholds
By 3 years after HAART initiation ( of all
children initiating HAART)
1st confirmed viral load gt1000 c/ml 1st confirmed viral load gt30,000 c/ml
Switch before reaching threshold 14 18
Switch within 6months of reaching threshold 3 1
Remain on first-line for gt6months after threshold 15 3
Median time to switch after thresholds 3.3 years 1.0 years

• Switching somewhere between 1000 and 30,000c/ml
• but no clear level

10
Conclusions

• Low rate of switching to second-line
• Children never achieving virological suppression
  switch faster than those who had achieved
  suppression
• Older children switch faster than younger
  children
• Children starting HAART more recently also switch
  faster
• Little consistency in CD4 and viral load
  thresholds at switch
• Children achieving virological suppression tend
  to switch at lower viral loads and higher CD4s
• but wide variation in both
• No clear viral threshold being used to trigger
  switch.

11
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

12
Acknowledgements Thanks to everyone providing
data to the NSHPC and CHIPS !! Republic of
Ireland Our Lady's Childrens 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 Childrens 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