Virological suppression/rebound, ART discontinuation and weight gain in children switching to dolutegravir while virally suppressed in the UK/Ireland: a propensity score analysis Siobhan Crichton, Intira Jeannie Collins, Anna Turkova, Alasdair Bamford, Caroline Foster, Hermione Lyall, Ali Judd on behalf of the Collaborative HIV Paediatric Study (CHIPS) Steering Committee 19 th July 2019
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Virological suppression/rebound, ART discontinuation
and weight gain in children switching to dolutegravir
while virally suppressed in the UK/Ireland: a propensity
score analysis
Siobhan Crichton, Intira Jeannie Collins, Anna Turkova, Alasdair
Bamford, Caroline Foster, Hermione Lyall, Ali Judd on behalf of the
Collaborative HIV Paediatric Study (CHIPS) Steering Committee
19th July 2019
MRC CTU at UCL
Conflicts of interest
Nothing to disclose
MRC CTU at UCL
Background
• Dolutegravir (DTG) was approved in Europe for treatment of HIV-1 for individuals age
≥12 years in January 2014 and extended to 6-<12 year olds in December 2016.
• It is part of the World Health Organization (WHO) recommended preferred first-line
and second/subsequent-line regimens in children.
• 30% of children and adolescents in paediatric care in the UK and Ireland and now on
DTG.
• Rapid weight gain has been reported in some adults starting DTG but data on
treatment outcomes in routine paediatric care are limited.
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Aim
To describe virological suppression, viral rebound, discontinuations and weight gain in
children switching to DTG with suppressed viral load and compare to outcomes in
children suppressed at switch to a new protease inhibitor (PI)-based regimen.
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Methods
Population: All children receiving paediatric HIV care in the UK and Ireland
followed up in the Collaborative HIV Paediatric Study (CHIPS).
Inclusion criteria:
– aged 6-<18 years
– treatment experienced at switch to 2NRTIs+DTG or boosted PI
– suppressed viral load (VL) (<50c/ml or <lower limit of detection) at time of switch (3 month before to 1 week after)
– switched between 2010 and 2018
Where there was >1 eligible PI regimen per child, the most recent was used
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Propensity scores (1)
• Randomised controlled trials (RCTs) are the gold standard for
assessing the effectiveness of an intervention.
- Randomisation ensures differences on observed and unobserved factors are
due to chance
• Propensity scores offer a method of estimating treatment effects in
non-randomised data.
• A propensity score (PS) is an individual’s probability of receiving a
specific treatment based on their (observed) characteristics.
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Propensity scores (2)
• In a group of individuals with the same propensity scores the
distribution of characteristics will be the same in those who were and
were not treated.
• PS often used to match individuals who are ‘treated’ to similar
‘untreated’ individuals.
• Other uses include weighting, stratification and adjustment.
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• We estimated propensity scores based on the following
characteristics at start of DTG/PI
– age
– sex
– time since ART initiation
– history of treatment failure
– prior AIDS event
– CD4 count
– BMI-for-age z-score
Propensity scores (3)
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Statistical analysis
• PS used to estimate the differences between DTG and PI regimens in
• Proportion suppressed (VL<50 or <LLD) at 6 and 12 months
• Hazard of confirmed viral rebound (2 consecutive VL≥50c/ml) or discontinuation in first 12 months
• Mean change in BMI-for-age z-score (zBMI*) at 6 and 12 months
• In sensitivity analyses, the analysis was repeated using a threshold of 400 to
define viral suppression/rebound.
*World Health Organization. Growth reference data for 5-19 years. WHO reference 2007.
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Ever on DTG
N=302
VL<50c/ml
n=119
on PI*
N=797
On PI+2NRTIs
aged 6 to <18 years
n=408
VL<50c/ml
n=181
* started new boosted PI since 2010
** children who also started an eligible DTG containing regimen with VL≤50c/ml were excluded
On DTG+2NRTIs
aged 6 to <18 years
n=175
n=32 aged ≥ 18 years
n=45 aged <6 years
n=136 ineligible regimens
n=117 treatment naïve
n=59 on DTG**
n=27 VL≥50c/ml
N=29 VL unknown n=187 VL≥50c/ml
N=40 VL unknown
n=28 aged ≥ 18 years
n=1 aged <6 years
n=2 exact age unknown
n=72 ineligible regimen
n=24 treatment naive
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Characteristics of young people on
DTG and PI based regimens
DTGN=119
PIN=181
Median[IQR] or n(%)
Male sex 56 (47%) 90 (50%)
Age (years) at first ART 4.9 [1.2, 9.8] 4.7 [1.1,8.7]