Agenda Introduction- Jessica Rodrigues, IATT Paediatric Treatment Optimization- George Silberry, Senior Technical Advisor for Pediatric HIV, OGAC Optimal.

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 RecommendationsFirst-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 + NVPAZT + 3TC + NVP

ABC + 3TC + NVPAZT + 3TC + EFVAZT + 3TC + NVPTDF + 3TC (or FTC) + EFVTDF + 3TC (or FTC) + NVP

AZT + 3TC + EFVAZT + 3TC + NVPTDF + 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

• Effective• Safe• Forgiving• Easy to take• Easy transition as children

grow

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

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

Rational sequencing of NRTI’s

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AZT

d4T

ABC

TDF

Thymidine Analogs

Cytidine Analogs

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

frRational Sequencing of NRTI’s

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 use after LPV/r failure in 1st line

Introduction of new agents: Raltegravir >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 ART for Children: Is a Public Health Approach Possible?

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Challenge SolutionIndividualized regimens based on resistance pattern

New guidance from WHO based on rational sequencing and availability of new drugs

Cost Affordable options should become available with increasing demand

Availability in RLS Programs are beginning to plan for introduction of third-line

(New Horizons)

Third-line ART for Children: Is a Public Health Approach Possible?