program for hiv prevention and treatment ird 174/phpt
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Program for HIV Prevention and Treatment IRD 174/PHPT. Cost-effectiveness of early infant HIV diagnosis and immediate antiretroviral therapy in HIV-infected childrenTRANSCRIPT
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Cost-effectiveness of early infant HIV diagnosis and immediate antiretroviral therapy in HIV-
infected children <24 months in Thailand
IJ Collins 1,2, J Cairns 3, N Ngo-Giang-Huong1, W Sirirungsi4, P Leechanachai4, S Le Coeur1, 5, N Kamonpakor6, J Mekmullica7, S Shabbar2, G Jourdain 1, M Lallemant 1,
for the Programme for HIV Prevention and Treatment (PHPT) study team1Institut de Recherche pour le Développement (IRD) UMI 174-PHPT, France - Faculty of Associated Medical Sciences, Chiang Mai University, Thailand - Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, USA, 2Faculty of Epidemiology and Population Health, London School of Hygiene & Tropical Medicine (LSHTM), UK;3Faculty of Public Health and Policy, LSHTM, UK; 4 Faculty of Associated Medical Sciences, Chiang Mai University, Thailand,5 Unité Mixte de Recherche 196 Centre Français de la Population et du Développement (INED-IRD-Paris V University), Paris, France, 6 Somdej Prapinklao Hospital, Thailand, 7 Bhuminbol Adulyadej Hospital, Thailand
Program for HIV Prevention and Treatment IRD
174/PHPT
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Background• In 2012, 290,000 children were newly infected with HIV. Without ART,
up to 50% will die by two years of age in resource limited settings.
• CHER trial: immediate ART in infants aged <12 weeks reduced mortality by 76% as compared to deferred treatment.
• WHO(2010) recommends immediate ART in HIV+ children <24 months. Early infant HIV diagnosis (EID) is essential for early ART.
• As maternal antibodies persist for up to 18 months, EID requires more complex and costly diagnosis tests.
• Estimated 35% of HIV-exposed infants received EID by 2 months-old. Coverage of ART in children is disproportionately low at 34%.
• No data on cost effectiveness EID and immediate ART. Important to inform decision makers facing competing health demands.
WHO Progress Report 2013, Violari et al. NEJM 2008.
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Objective
To assess the cost effectiveness of early infant HIV diagnosis and immediate ART in HIV infected children, in a non-breastfed population in Thailand, comparing:
1) EID and immediate ART in HIV+ children <24 months (Early-Early)
2) EID and deferred ART based on immune/clinical criteria (Early-Late)
3) Clinical based diagnosis or serology at 18 months, and deferred ART based immune/clinical criteria (Late-Late, Reference)
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Setting: Thailand
• Free ART under universal health coverage.• Pilot EID programme from 2007, 68% coverage. • DNA PCR using dried blood spot (DBS) accessible
for rural hospitals and community health clinics.• First test at 2 months or earlier if symptomatic.
If test positive repeat immediately, if negative repeat at 4 months.
• Estimated cost EID: $32 per test (including infrastructure, human resources, QA etc.)
Naiwatanakul et al. IAS 2012; Sirirungsi et al. Pead HIV Workshop 2013.
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Methods• Decision tree for EID and ART pathway: all HIV exposed children• Markov cohort model: HIV infected who initiate ART• Health care provider’s perspective, costs US$ 2011 (PPP)• Time horizon: up to 40 years on ART. Discount rate 3%.• Incremental cost effectiveness ratio (ICER) per life year gained =
Incremental cost--------------------------------------
Incremental life year gained (LYG)
• ICER less than 1xGDP (US$ 4,420) was considered as cost effective. • Univariate and Probabilistic Sensitivity Analysis (1000 runs).
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Survival and cost estimates: PHPT cohort
• PHPT observational cohort study in a network of public hospitals. • Two modes of entry:
– Birth cohort: EID at birth and 6 weeks – Referred cohort: diagnosed after symptomatic at older ages All children started ART based on immune/clinical criteria
• Mortality pre-ART and on ART at up to 5 years of follow up1 • Cost of ART: hospitalization2 and ART drug costs 3.
• Base case: weighted average of children starting ART under and over 12 months.
1 Collins et al. CID 2008, 2. Collins et al. AIDS 2012, 3. Collins et al. JAIDS in press.
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Survival and cost estimates: PHPT cohort
• PHPT observational cohort study in a network of public hospitals. • Two modes of entry:
– Birth cohort: EID at birth and 6 weeks– Referred cohort: diagnosed after symptomatic All children started ART based on immune/clinical criteria
• Mortality pre-ART and on ART at up to 5 years of follow up1 • Cost of ART: hospitalization2 and ART drug costs 3.
• Base case: weighted average of children starting ART under and over 12 months.
1 Collins et al. CID 2008, 2. Collins et al. AIDS 2012, 3. Collins et al. JAIDS in press.
>> Early-Late
>> Reference
>> Early-Early: CHER study risk reduction in disease progression
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Key parametersParameter Estimate 95% CI Source
Rate of MTCT 3.9% 2.2-6.6 Plaipat 2003
Coverage of EID 68% 47-79 Naiwatanakul 2012
Confirmation of EID 78% 47-85 Naiwatanakul 2012
Linkage to HIV care within 3 months of EID 73% 64-82 Sirirungsi 2013
Initiated ART within 3 months of linkage 85% 79-92 Sirirungsi 2013
Sensitivity and specificity of DNA PCR 100% Ngo 2008.
Risk reduction in disease progression on ART in Early Early (apply for 12-months)
0.25 0.15-0.41 Violari 2008
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Results: Model validationPHPT cohort survival (95% CI) Model projected survival (95% CI)
1 year 5 years 1 year 5 years
Children <12 months at start of ART
Early-Early - - 93.6% 90.0%
Early-Late 84.1 (69.5-92.1) 74.1 (58.0-92.1) 82.0% 73.6%
Reference 84.6 (51.2-95.9) 84.6 (51.2-95.9) 78.1% 67.8%
Children ≥12 months at start of ART
Early-Early - - 97.4% 95.0%
Early-Late 98.5 (89.6-99.8) 96.7 (87.4-99.2) 97.4% 95.0%
Reference 95.3 (92.8-96.9) 93.6 (90.4-95.6) 96.0% 92.5%
Projected survival was within 2% of PHPT cohort estimate among older children. Poorer projections among infants in Reference arm, most likely due to small sample size.
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Results: ICER
• Main benefit of Early-Early was reduced risk of pre-ART deaths and early mortality on ART.
• Over 90% of programme cost was lifetime cost of ART. Reductions in MTCT will substantially reduce programme cost.
Programme model Early-Early Early-Late Reference Total Cost (All children) $4.0 million $3.1 million $2.4 million
Mean LYG (undiscounted) of HIV+ child 17.8 years (29.1)
14.3 years (22.8)
13.3 years (21.0)
Discounted mean life time costs of HIV+ child
$17,128 $13,441 $10,426
ICER over Reference $1,489 $2,929 -
ICER over Early-Late $1,067 - -
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Rate of HIV infection
Coverage of Early HIV diagnosis
Confirmation of Early HIV Diagnosis
Initiate on ART in EE arm
Risk of developing symptoms <12mo
Risk of developing symptoms 12-24 mo
Risk reduction in disease progression
Cost of early HIV diagnosis
Cost ART Year 1-5
Cost of ART Y5+
Cost third line ART
Cost of ART monitoring
Hospitalization cost (>Y1)
Outcome discount
Cost discount
-600 -400 -200 0 200 400 600 800 1000 1200
Univariate Sensitivity Analysis: Effect of input parameter high and low estimate on ICER in Early-Early versus Reference arm
Low estimateHigh estimate
Change in ICER ($ per LYG)
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Rate of HIV infection
Coverage of Early HIV diagnosis
Confirmation of Early HIV Diagnosis
Initiate on ART in EE arm
Risk of developing symptoms <12mo
Risk of developing symptoms 12-24 mo
Risk reduction in disease progression
Cost of early HIV diagnosis
Cost ART Year 1-5
Cost of ART Y5+
Cost third line ART
Cost of ART monitoring
Hospitalization cost (>Y1)
Outcome discount
Cost discount
-600 -400 -200 0 200 400 600 800 1000 1200
Univariate Sensitivity Analysis: Effect of input parameter high and low estimate on ICER in Early-Early versus Reference arm
Low estimateHigh estimate
Change in ICER ($ per LYG)
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Results: Probabilistic sensitivity analysis
0.00 1.00 2.00 3.00 4.00 5.00 6.00 7.00 8.00$0
$5,000
$10,000
$15,000
$20,000
$25,000
$30,000
Early LateEL Probabilistic meanEarly EarlyEE Probabilistic mean
Incremental LYS
Incr
em
en
tal C
ost
(U
SD
)
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$0 $1,000 $2,000 $3,000 $4,000 $5,000 $6,000 $7,0000.00
0.10
0.20
0.30
0.40
0.50
0.60
0.70
0.80
0.90
1.00
Standard
Early-Late
Early Early
Value of ceiling ratio
Pro
bab
ilit
y co
st-e
ffec
tive
Probability of cost effectiveness by defined threshold per LYG
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Subgroup analysis: by risk of perinatal transmission
$0 $500 $1,000 $1,500 $2,000 $2,500 $3,000 $3,500 $4,0000.00
0.10
0.20
0.30
0.40
0.50
0.60
0.70
0.80
0.90
1.00
No PMTCT (37.5%)
ZDV only (9.7%)
ZDV and other ARV (3.9%)
PHPT-2 (1.9%)
Cost effectiveness threshold
Pro
ba
bil
ity
co
st-
eff
ec
tiv
e
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Limitations
• Generalizability: non breastfed population, context specific coverage, retention, costs and cost-effectiveness threshold.
• Quality of life: scarce data in children, not capture additional benefits e.g. preservation of immune function, avert neurodevelopmental damage, benefit of EID etc.
• Assumed 100% sensitivity and specificity of DNA PCR, unclear if this will vary with exposure to maternal HAART for PMTCT (Shapiro et al. IAS 2011).
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Summary
• EID and immediate ART in HIV infected children <24 months was cost effective in the non-breastfed population in Thailand.
• Results were robust to sensitivity analyses and was cost effective even when low rates of MTCT.
• Supports efforts for continued scale up of EID and improved linkage with ART services.
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Acknowledgements• Program for HIV Prevention and Treatment (IRD-PHPT)• Participating hospitals• Faculty of Associated Medical Sciences, Chiang Mai University• Global Fund to Fight AIDS, TB and Malaria• Oxfam GB• MRC DTA Studentship, UK
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Decision tree : pathway for HIV diagnosis and referral for ART.