1. Access to Paediatric ARV Formulations Provisions for Children

2. DEMAND : When to start ; What to start with …. WHO Guidelines exist For Prevention of Mother to Child Transmission: –Guideline for mothers with indications for initiation of treatment who may become pregnant –Mothers on ART who become pregnant, and infants –HIV infected pregnant women with or without indications for ART, and infants etc For Treatment and Care: First Line –Preferred option for children (zdv or d4T) + 3TC + NVP –Guideline for children on TB treatment regiments containing rifampicin, substitute NVP for EFV For Treatment and Care: Second Line –Guidelines for children with treatment failure ABC + ddI + PI

3. UNICEF SUPPLY DIVISION ARV formulations available ………… Product portfolio include: ARVS 42 formulations in 75 different presentations, 30 - 40% can be used for children <14 HIV tests, CD4, CD8, Viral load including PCR equipment ( 2 suppliers )

4. FIRST LINE / PMTCT:ARV Formulations available... TreatmentProducts availablePrice (US $ / 100ml) PMTCT/ 1st LineInnovatorGenericInnovator *Generic # D4TYes 0.751.50 ZDVYes 2.961.45 3TCYes 2.801.20 NVPYes 7.291.20 EFVYesNo9.45 - 15.12 * Mostly current ACCESS prices unless range indicated, # Not necessarily WHO prequalified

5. FIRST LINE / PMTCT Operational Characteristics of available ARV Formulations (WHO prequalified/FDA approved) Products available (volume) Storage & other considerations PMTCT/ 1st Line InnovatorGeneric Fridge ?Other ZDV240ml100, 200mlNo 100mg caps available d4T200ml-Yes Supplied as pwdr, 15 mg caps 3TC240ml100, 240mlNo Tabs split, crushed NVP240ml20*, 25,100mlNo Need 0,6ml for PMTCT EFV180mlNo 50mg caps opened * Only available in donation programme, with dispensing syringe

6. FORMULATIONS TO PROVIDE PMTCT SERVICES Key challenges …. Nevirapine suspension (10mg/ml) : –Commercially available as 240ml –Donation programmes supply 20ml or 25ml –Bottles are adapted with fitted caps to facilitate dispensing –For PMTCT, need 0,6ml per day ? –Dispensing syringe : BAXA Donation Zidovudine oral liquid (10mg/ml) –Commercially available as 100ml, 200ml, 240ml bottle –For PMTCT, need approximately 35ml per week ? Lamivudine oral liquid (10mg/ml) –Commercially available as 100ml, 240ml –For PMTCT, need approximately 25ml per week ?

7. SECOND LINE / PMTCT ARV Formulations are available …… TreatmentProducts availablePrice (US $ / 100ml) 2nd LineInnovatorGenericInnovator *Generic # ABCYesNo13.05 ddIYesNo10.66 LPV/rYesNo13.70 – 136.70 NFVYesNo 30.15 / 144 g 35.00 / 144g * Mostly current ACCESS prices unless range indicated, # Not necessarily WHO prequalified

8. SECOND LINE Operational Characteristics of available ARV Formulations Treatment Products available (volume) Storage & other considerations 2 nd Line InnovatorGenericFridge ?Other ABC240ml-NoTabs crushed ddI237ml-No Need antacid, Chew tabs 25,50mg LPV/r5x60ml-YesNeed cold shipment NFV144g pwd-NoTabs split, crushed

9. ESTIMATING THE NUMBER OF TREATMENTS NEEDED STEP 1: Estimated number of births, existing death-rates, HIV prevalence in ANC settings STEP 2: Estimated PMTCT coverage and transmission rates = estimated HIV positive infants born = transmission through breast feeding STEP 3: What is the chance of survival ? Morbidity ? Mortality Coverage with cotrimoxazole prophylaxis STEP 4: Estimated number of children at different ages eligible for treatment (assumptions around disease progression) STEP 5: Reality check – who will enrol them into treatment, etc …

10. NUMBER OF INFECTED CHILDREN ALIVE AT SELECTED AGES, birth cohort ± 300,000 (effect of COTRIMOXAZOLE [TMP-SMX] prophylaxis and/or ART for symptomatic) Marie-Louise Newell, Kirsty Little, Madeleine Bunders (Ghent-IAS Group on HIV infection in women and children)

11. NUMBER OF INFECTED CHILDREN ALIVE AND ELIGIBLE FOR ART AT SELECTED AGES (effect of COTRIMOXAZOLE [TMP-SMX] prophylaxis and/or ART for symptomatic) Marie-Louise Newell, Kirsty Little, Madeleine Bunders (Ghent-IAS Group on HIV infection in women and children)

12. PUTTING IT IN CONTEXT: NUMBER OF INFECTED CHILDREN ALIVE AND ELIGIBLE FOR ART AT SELECTED AGES, BIRTH COHORT 300,000 HIV+ infants (effect of COTRIMOXAZOLE [TMP-SMX] prophylaxis and/or ART for symptomatic) Marie-Louise Newell, Kirsty Little, Madeleine Bunders (Ghent-IAS Group on HIV infection in women and children)

13. ARV liquid formulations can become expensive.. Regimen Paediatric Cost per month Cost Per month Cost per day Cost per day Total generic* Costs Total Branded Costs originalgenericoriginalgeneric1 yr5 yrs1 yr5 yrs ZDV+3TC+NVP* (<3yrs/10kg) 54.8315.621.830.52 185.30 926650.64 3,253 ZDV+3TC+NVP* (>3yrs/20kg) 113.9238.383.801.28 455.422,2771351.83 6,759 d4T*+3TC+NVP* (<3yrs/10kg) 42.3611.971.410.40 142.04 710502.68 2,513 d4T*+3TC+NVP* (>3yrs/20kg) 86.1481.3923.440.78 278.18 1,3911022.20 5,111 ZDV+3TC+EFV* (10kg with liquid) 44.5337.341.481.24 443.13 2,216528.39 2,642 ZDV+3TC+EFV* (10kg with tab) 32.9825.791.100.86 306.07 1,530391.33 1,957 ZDV+3TC+EFV* (20kg with liquid) 85.7658.412.861.95 603.15 3,4661017.65 5,088 ZDV+3TC+EFV* (20kg with tab) 72.6745.322.421.51 537.82 2,689862.32 4,312 ZDV+3TC+ABC* (<3yrs/10kg) 62.4949.102.081.64 582.59 2,913741.56 3,708 *no generic Note: calculations based on 10kg and 20kg scenarios

14. MSF Paper: Current situation regarding prices and availability of specific children formulations … Cost of treatment drops when switching to adult formulations: Peak around 14kg bodyweight Using tablets for a child (20 kg) reduces the cost per treatment per year nearly 8 times: – (d4T / 3TC / NVP ) Best generic price/y$ 222$16 Best innovator price/y $ 508 $27.24 Managing the switch – increases complexities in resource poor settings

15. ARV Formulations available, but …. More expensive than adult formulations No fixed dose combinations Estimating needs are problematic Weight guided dosing will assist care-givers Some need cold storage, shipment Distributing glass bottles has it’s problems Taste of formulations, bulk of supplies

16. RECOMMENDATIONS FROM NOVEMBER 2004 WHO/UNICEF CONSULTATION With currently available formulations, children CAN and SHOULD BE treated –Simplified treatment guidelines are in progress; –weight based dosing, eligibility to treatment done, should be available soon ! Greater advocacy is needed for access to appropriate formulations for both PMTCT and HIV Care and Treatment Demand forecasting vs HOW MANY CHILDREN CAN WE REACH TOMORROW ? Improved diagnostics …..