Agenda
• Introduction- Jessica Rodrigues, IATT
• Paediatric Treatment Optimization- George Silberry, Senior
Technical Advisor for Pediatric HIV, OGAC
• Optimal regimen selection and sequencing- Elaine Abrams
Senior Director for Research, ICAP
• Optimal formulation selection- Marc Lallemant Head of
Pediatric HIV, DNDi and Janice Lee Project Manager for
Pediatric HIV, DNDi
• Optimizing supply chain management- Nandita Sugandhi,
Senior Clinical Advisor, CHAI and Marianne Gauval
Associate Director of Pediatric Access, CHAI
• Q&A/Discussion- Surbhi Modi, Maternal and Infant HIV
Team Lead, CDC
2013 WHO Recommendations
First-line Antiretroviral Regimens
Children < 3 years
Children 3 years to < 10
years
Adolescents > 10 years
Preferred
ABC + 3TC + LPV/r
or
AZT + 3TC + LPV/r
ABC + 3TC + EFV
TDF + 3TC + EFV
Alternative
ABC + 3TC + NVP
AZT + 3TC + NVP
ABC + 3TC + NVP
AZT + 3TC + EFV
AZT + 3TC + NVP
TDF + 3TC (or FTC) + EFV
TDF + 3TC (or FTC) + NVP
AZT + 3TC + EFV
AZT + 3TC + NVP
TDF + 3TC (or FTC) +
NVP
At program level generally fewer choices are available:
•Simplifies guidance for health care workers
•Streamlines procurement and supply chain
Choosing a Preferred Pediatric First Line
Children
< 3 years
•
•
•
•
•
Effective
Preferred ABC + 3TC +
LPV/r
Safe
Or
Forgiving
AZT + 3TC +
LPV/r
Easy to take
Easy transition as children
grow
Children
3 years to
< 10 years
Adolescents
> 10 years
ABC + 3TC +
EFV
TDF + 3TC +
EFV
Life-long Treatment: Rational Sequencing
of Regimens Starting in Childhood
• Objective to achieve simplified
recommendations harmonized across all
age groups
• Rational sequencing of drugs and drug
regimens for a public health approach
• From first to second to third line
• From infancy to adulthood
• Considerations for guidance for regimen
transitions as children age into adulthood
frRational
SequencingofofNRTI’s
NRTI’s
Rational sequencing
AZT
Thymidine Analogs
d4T
ABC
Cytidine Analogs
TDF
Thymidine analogs may be MORE effective after failure on cytidine
analogs; cytidine analogs may be LESS potent after thymidine analog
failure and accumulation of TAMS
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First-line Determines Second-line
WHO, 2013
Simplifying Second-line ART
Challenge
Solution
Low recognition of
treatment failure
Expanded use of VL for
routine monitoring
Currently used 2nd line
regimens don’t support
adherence
Simpler options are
available (e.g. ATV/r for
older children)
Confusion about what to
Introduction of new
use after LPV/r failure in 1st agents: Raltegravir
line
>4weeks, dolutegravir >12
yrs, darunavir for >3 years
Raltegravir
• Dosing established in pediatrics for ≥ 4 weeks of age
• Pediatric formulations available:
– Powder for suspension for <10kg
– Chewable tab for >10kg
• Twice daily dosing
• RTG dosing with TB co-treatment
under study
• Currently limited availability
• Limited interest for adults
Good option but not favourable for harmonization
Dolutegravir
• Low dose/kg is good for infants and children
• High genetic barrier ideal for poorly adherent children and
adolescents
• Once daily dosing and good toxicity profile
• Only approved for ≥12 years of age
• Dispersible formulation in development
• Not FDC ready yet and only planned in
combination with abacavir
• Ongoing and planned studies for children
IMPAACT 1093 & ODYSSEY
Ideal for harmonization but not yet a reality
:
Third-line
forChildren:
Children:
Third-line ART
ART for
a PublicHealth
Health Approach
Approach Possible?
Is Is
a Public
Possible?
Challenge
Solution
Individualized regimens
based on resistance pattern
New guidance from WHO based on
rational sequencing and availability
of new drugs
Cost
Availability in RLS
Affordable options should become
available with increasing demand
Programs are beginning to plan for
introduction of third-line
(New Horizons)
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