Important to consider availability of child- friendly formulations Easier for HCW’s to prescribe for all ages Easier for caregivers to administer to infants and children Easier for infants and children to adhere Easier to manage supply chain

Target Product Profile for Paediatric ARV’s IDEAL CHARACTERISTICS All ARVs in one presentation Simple to use with water, milk or food Good taste No fridge needed Suitable for infants (<2 months - 3 years) TB-treatment compatible Affordable for governments

Changes in WHO Guidelines 2013 For all children <3yo, start LPV/r based regimen regardless of NNRTI exposure NVP based ART LPV/r + 2 NRTIs FDCs available Baby and junior dosing Scored tablets Can be crushed/dispersed Easy dosing Liquid only for young children Bitter taste Toxic excipients 42% ethanol 15% propylene glycol Requires cold chain Heavy to carry, hard to hide Difficult dosing Need for RTV super-boosting in TB/HIV co-infection

Product Profile: LPV/r Oral Pellet (40mg/10mg) per capsule 4 Main characteristic: Heat-stable (storage 30°C), solid, no alcohol content, pellets in capsule to be opened LPV/r pellet was USFDA tentatively approved in May 2015 for use in children >5kg. Main issue is that acceptability of younger infants not known. Safety of dosing in infants kg has been demonstrated in a small number of infants in CHAPAS- 2. Currently not registered in any country in the world. Dossier submission underway in 18 countries. DNDi started LIVING study in Kenya in September 2015 to learn about acceptability and feasibility of formulation

Product Profile: Simplified Weight Band Dosing Schedule for LPV/r 5 LPV/r oral pellets are administered twice daily (every 12 hours). LPV/r SHOULD NOT be administered once daily (every 24 hours) to children <18 years of age. 10 The USFDA has approved the use of pellets in children ≥ 5kg, though the safety of dosing infants kg has been demonstrated in a small number of infants in CHAPAS-2. The pellets may be administered in this weight band if infants are developmentally able to swallow them.

Administration instructions: LPV/r Oral Pellet (40mg/10mg) 6 Please refer to Package Product Insert and FACT SHEET on LPV/r Oral Pellets for more detailed information. Do’s: Capsules containing pellets should be opened and administered to child Vehicle of administration: water, milk/breast milk or semi solid food Don’t’s: Do not dissolve pellets in water or hot food (bitter taste) Do not chew pellets (bitter taste) For infants and children already on soft food ie. >6 months : Twist and open capsule to release pellets on a spoon containing soft food (eg. porridge, yogurt etc.) Wash down pellets in mouth with additional food or water. Repeat until entire dose required for child administered For infants not yet taking solid food ie. < 6 months Twist and open capsule to release pellets on a small container or cup Put small quantity of pellets directly into child’s mouth and breast feed or formula feed OR Put pellets in expressed breast milk or formula feed in a spoon and feed the child continued by beast feeding or formula feeding. Repeat until all pellets are administered

LIVING Study Prospective Study of Lopinavir Based ART for HIV Infected childreN Globally * Open-label, prospective, non- randomised, non comparative, multi- center, multi-country study Provide early access to solid based LPV/r regimen for HIV infected children with LPV/r pellets and NRTIs FDC, then switch to 4-in-1 when clinical batch available Minimum 1 year follow up Countries involved: Kenya, Uganda, Tanzania, Malawi, Zimbabwe, South Africa, francophone Africa and where interested implementing partners are found. Recruitment started in Kenya in September 2015 with positive feedbacks from caregivers with children who were on LPV/r syrup before switching 7 Screening Enrollment ABC/3TC or AZT/3TC 60/30mg and LPV/r 40/10mg pellets Follow-up at 2 wks, 1 mth, 3 mths, every 3 mths

Testimonies from healthcare workers “All 9 mothers recruited are excited to use pellets which can be put into food and swallowed. No difficulty reported in follow up.” – Dr. Karen Mbruru, Paediatrician “Drawing syrup using syringes is difficult for mothers. Pellets are easy to store and easy to calculate adherence.” – Nypha, Pharmacy technician “Mothers are happy to see an alternative to syrup because carrying bottles of syrups is cumbersome as they may break or leak.” – Sara Mwange, senior nurse “One mother explained to other mothers that her child is put in a study and not given the bitter thing prompting other mothers to ask about this study.” - Nypha, Pharmacy technician

New Product Intro A new heat-stable, child friendly formulation of LPV/r is now available Guidance on administration and supply planning available from IATT