1. Supporting access to quality paediatric ARVs Atieno Ojoo Technical Specialist, Pharmaceuticals UNICEF Supply Division IAS satelite session on Essential Medicines, SR5 Wed 6 th August 2008

2. PRESENTATION OUTLINE Introduction/background Challenges with paediatric ARVs Current solutions Recommendations for the future

3. Introduction: UNICEF HIV focus areas Prevention of Mother to Child Transmission Paediatric treatment and care Preventing infections among adults and youth Protection and support to children affected by HIV/AIDs

4. Major challenges Limited use of timely diagnosis for kids < 18 months. DBS costly in terms of sample transport and lab works Limited safety and efficacy data Limited age-appropriate formulations Palatability concerns- e.g.LPV/r liquid High cost especially liquid formulations No standardized methods to adapt adult formulations for children. Limited standardized dosing and dose measurements- Weight, BSA, age? Dose adjustment with growth What is a teaspoonful? Desert spoon? Table spoon?

5. Challenges: Paediatric ARV market Large difference in demand for adult vs. pediatric ARVS –UNAIDS data 2006: –People living with HIV/AIDS needing treatment: 7.1 million –Children needing treatment: 780,000* Limited experience with pediatric compared to adult treatment  Expected decrease in incidence of paediatric HIV with increase uptake of PMTCT programmes? Reduced incentive to make paediatric ARVs for treatment  Limited paediatric HIV case survival data: what is the value added of putting children on ARV?  * current figures not available in UNAIDS 2007 data

6. UNICEF PROCUREMENT OF ARVS

7. GAVI, GFATM, PMI, UNITAID National Regulatory Authorities World Bankprivate sector Humanitarian Clusters SWAPS/PRSPs WFP, UNHCR, UNICEF, UNFPA, WHOIntegrated Campaigns PATHIFRC, Oxfam, MSF, CARE, World Vision, SCF Governments- several ministriesCold Chain Mid-level Management Traininghard-to-reach Customs Clearance Transport Equipment Bilateralsroutine delivery Many players: difficult to leverage on volumes

8. Registration, Marketing, patents, pricing Challenges in medicines supply for children Demand Creation Supplier Agreements Financing Receipt, Storage, Distribution Forecasting Quality Assurance Effective Use Product Procurement Product Selection Monitoring Calculating the quantities we should/can buy … Must be done

9. Challenges with prescribing, dispensing, adherence –Prescription is for AZT 125mg bd. What to dispense?(Patient on other ARVs too) Can Child swallow AZT 100mg Caps? (Age > 1 yr) –YES, then consider –100 mg Cap X 2 daily X 30 days = 60 Capsules AND –2.5ml Syrup X 2 daily X 30 days = 150ml –If child had 5 caps and ¼ of 200ml bottle left… Dispense 55 caps AZT 100mg or as per next appointment date AND 1 Bottle AZT 200ml because syrup is only stable for 1/12 once opened. OR 12.5ml syrup X2 daily X 30 days=750ml, 4 bottles of 200ml for one month

10. How we try to solve the problems 1.Splitting tabs or dividing caps powder Challenge if tablet not scored:1/2 of d4T+3TC+NVP. Needs tablet cutter? Cost of tablet cutter? To be given to every patient? Some tablets designed to be swallowed whole cannot be split 2.Suspend crushed tablets in water Lack of facilities for hygienic preparation Accurate volume but unreliable dose, some stick to spoon Solubility challenge: 125%. 3.Administering liquid formulations Reduced shelf life after opening Taste problems, not easily portable Large volumes of liquid to be taken per dose

11. Pharmaceutical care challenges Counseling to care giver and child. Caregivers often change Palatability, stability Dose scheduling to daily routine e.g. school, meal times, adjusting for growth, weight gain Caregivers always complain of being made “pharmacists”

12. Too much to carry and take… Child: too many bottles Adult

13. Quotable quotes: 4 th IAS Sydney 2007 Presentation by MSF on data from Uganda –Good clinical results but sub-optimal virological outcomes. "Our treatment outcomes in children are a reflection of how difficult it has been to treat children with drugs that aren't designed for them," said Dr. Myrto Schaefer, Paediatric HIV/AIDS Advisor for MSF. "Because appropriate formulations have not been available for children, we've had to treat them by cutting adult tablets in two, or give them syrups that are hard to measure and swallow. This approximate method of dosing and administration may be what is contributing to the less-than-ideal virological outcomes we are finding."

14. Current solutions: Latest Solid dose formulations d4T/3TC 6mg/30mg d4T/3TC 12mg/60mg d4T/3TC/NVP 6mg/30mg/50mg d4T/3TC/NVP 12mg/60mg/100mg AZT/3TC/NVP 60mg/30mg/50mg Lopinavir/ritonavir 100mg/25mg Abacavir 60mg tablets

15. Recommendations: What needs to be done differently within health systems? 1.Support for missing paediatric essential medicines −Advocacy for paediatric formulations to industry −Support for appropriate drug development e.g special patent extensions for paed clinical studies (EMEA, USFDA) −UNITAID support 2.Health systems improvement –Increased integration of HIV into existing health systems –Increased access to & use of existing quality medicines e.g. CTX, AZT, NVP –Guidance on PSM of paediatric medicines