January 2006 Access to Paediatric ARV formulations Access to Paediatric ARV Formulations The plight of Children

January 2006 Access to Paediatric ARV formulations UNICEF SUPPLY DIVISION ARV formulations available ………… Product portfolio include: ARVS 42 formulations in 75 different presentations, % can be used for children HIV tests, CD4, CD8, Viral load including PCR equipment ( 2 suppliers )

January 2006 Access to Paediatric ARV formulations Access to paediatric ARV formulations depends on effective supply chain management Demand Supplier Agreements Financing Receipt, Storage, Distribution Forecasting Quality Assurance Effective Use Product Procurement Product Selection Monitoring

January 2006 Access to Paediatric ARV formulations 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

January 2006 Access to Paediatric ARV formulations FIRST LINE / PMTCT:ARV Formulations available... TreatmentProducts availablePrice (US $ / 100ml) PMTCT/ 1st LineInnovatorGenericInnovator *Generic # D4TYes – ZDVYes TCYes NVPYes EFVYesNo * Mostly current ACCESS prices unless range indicated, # Not necessarily WHO prequalified

January 2006 Access to Paediatric ARV formulations FIRST LINE / PMTCT Operational Characteristics of available ARV Formulations 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

January 2006 Access to Paediatric ARV formulations PRODUCT SELECTION : When to start ; What to start with …. For Prevention of Mother to Child Transmission: For infant: Nevirapine (NVP)single dose 0,6ml Zidovudine (ZDV)4mg/kg 2x daily, for 1 week Lamivudine (3TC)2mg/kg 2x daily, for 1 week See

January 2006 Access to Paediatric ARV formulations 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 ?

January 2006 Access to Paediatric ARV formulations SECOND LINE / PMTCT ARV Formulations are available …… TreatmentProducts availablePrice (US $ / 100ml) 2nd LineInnovatorGenericInnovator *Generic # ABCYesNo13.05 ddIYesNo LPV/rYesNo13.70 – NFVYesNo / 144 g / 144g * Mostly current ACCESS prices unless range indicated, # Not necessarily WHO prequalified

January 2006 Access to Paediatric ARV formulations 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

January 2006 Access to Paediatric ARV formulations FORECASTING : When to start ; What to start with …. For Treatment and Care: First Line Variations of Zidovudine (ZDV)< 4 weeks: 4mg/kg 2x daily 4 wks – 13 years: 180mg/m 2 /dose 2x daily Stavudine (d4T)< 30kg: 1mg/kg/dose 2x daily Lamivudine (3TC)< 30 days: 2mg/kg 2x daily, then 4mg/kg 2x daily Nevirapine (NVP)15 – 30 days: once daily dose 5mg/kg 30 days – 13 years: 120mg/m 2 /dose once a day for 2 weeks, then mg/m 2 /dose 2x daily Efavirenz (EFV)Only > 3 years, > 10kg

January 2006 Access to Paediatric ARV formulations FORECASTING : When to start ; What to start with …. For Treatment and Care: Second Line Variations of Abacavir (ABC)< 16yrs or < 37,5kg: 8mg/kg 2x daily Didanosine (ddI)< 3 months : 50mg/m 2 /dose 2x daily 3 months – 13 yrs : mg/m 2 /dose 2x daily, or 240mg/m 2 /dose once a day Lopinavir/ritonavir 6 months – 13 years: 225mg/m 2 LPV, plus (LPV/r) 57,5 mg/m 2 ritonavir 2x daily, or weight based Nelfinavir (NFV)< 1 yr: 50mg/kg/dose 3x daily, or 75mg/kg/dose bd 1 yr - 13 yrs: 55 – 65 mg/kg/dose 2x daily

January 2006 Access to Paediatric ARV formulations 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 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 …

January 2006 Access to Paediatric ARV formulations 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)

January 2006 Access to Paediatric ARV formulations 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)

January 2006 Access to Paediatric ARV formulations 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)

January 2006 Access to Paediatric ARV formulations 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) , ,253 ZDV+3TC+NVP* (>3yrs/20kg) , ,759 d4T*+3TC+NVP* (<3yrs/10kg) , ,513 d4T*+3TC+NVP* (>3yrs/20kg) , ,111 ZDV+3TC+EFV* (10kg with liquid) , ,642 ZDV+3TC+EFV* (10kg with tab) , ,957 ZDV+3TC+EFV* (20kg with liquid) , ,088 ZDV+3TC+EFV* (20kg with tab) , ,312 ZDV+3TC+ABC* (<3yrs/10kg) , ,708 *no generic Note: calculations based on 10kg and 20kg scenarios

January 2006 Access to Paediatric ARV formulations 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

January 2006 Access to Paediatric ARV formulations 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

January 2006 Access to Paediatric ARV formulations 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 …..

January 2006 Access to Paediatric ARV formulations Access to paediatric ARV formulations depends on effective supply chain management Demand Supplier Agreements Financing Receipt, Storage, Distribution Forecasting Quality Assurance Effective Use Product Procurement Product Selection Monitoring

January 2006 Access to Paediatric ARV formulations Access to paediatric ARV formulations depends on effective supply chain management Demand Creation Supplier Agreements Financing Receipt, Storage, Distribution Forecasting Quality Assurance Effective Use Product Procurement Product Selection Monitoring Calculating the number of bottles we should/can buy … We need partners to complete the cycle