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 yearsChildren 3 years to < 10 years Adolescents > 10 years PreferredABC + 3TC + LPV/r or AZT + 3TC + LPV/r ABC + 3TC + EFVTDF + 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 Effective Safe Forgiving Easy to take Easy transition as children grow Children < 3 years Children 3 years to < 10 years Adolescents > 10 years PreferredABC + 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 5 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

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