Access to Paediatric ARV Formulations

Provisions for Children

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

UNICEF SUPPLY DIVISIONARV 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 )

FIRST LINE / PMTCT:ARV Formulations available...

Treatment Products available Price (US $ / 100ml)

PMTCT/ 1st Line Innovator Generic Innovator * Generic #

D4T Yes Yes 0.75 1.50

ZDV Yes Yes 2.96 1.45

3TC Yes Yes 2.80 1.20

NVP Yes Yes 7.29 1.20EFV Yes No 9.45 - 15.12 * Mostly current ACCESS prices unless range indicated , # Not necessarily WHO prequalified

FIRST LINE / PMTCTOperational Characteristics of available ARV Formulations(WHO prequalified/FDA approved)

Products available(volume)

Storage & other considerations

PMTCT/ 1st Line Innovator Generic

Fridge ? Other

ZDV 240ml 100, 200ml No 100mg caps available

d4T 200ml - Yes Supplied as pwdr, 15 mg caps

3TC 240ml 100, 240ml No Tabs split, crushed

NVP 240ml 20*, 25,100ml No Need 0,6ml for PMTCT

EFV 180ml No No 50mg caps opened

* Only available in donation programme, with dispensing syringe

FORMULATIONS TO PROVIDE PMTCT SERVICESKey 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 ?

SECOND LINE / PMTCTARV Formulations are available ……

Treatment Products available Price (US $ / 100ml)

2nd Line Innovator Generic Innovator * Generic #

ABC Yes No 13.05

ddI Yes No 10.66

LPV/r Yes No 13.70 – 136.70

NFV Yes No30.15 / 144 g 35.00 / 144g

* Mostly current ACCESS prices unless range indicated , # Not necessarily WHO prequalified

SECOND LINEOperational Characteristics of available ARV Formulations

Treatment

Products available(volume)

Storage & other considerations

2nd Line Innovator Generic Fridge ? Other

ABC 240ml - No Tabs crushed

ddI 237ml - NoNeed antacid,

Chew tabs 25,50mg

LPV/r 5x60ml - Yes Need cold shipment

NFV 144g pwd - No Tabs split, crushed

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 ? MortalityCoverage 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 …

NUMBER OF INFECTED CHILDREN ALIVE AT SELECTED AGES, birth cohort ± 300,000

(effect of COTRIMOXAZOLE [TMP-SMX] prophylaxis and/or ART for symptomatic)

300000

236,274210,881 196,736

171,106

194,045

144,413119,596

74,6320

100000

200000

300000

BIRTH Age 1 Age 2 Age 5 Age 10

no TMP, no ARV

with ARV, no TMP

with TMP. No ARV

Marie-Louise Newell, Kirsty Little, Madeleine Bunders (Ghent-IAS Group on HIV infection in women and children)

NUMBER OF INFECTED CHILDREN ALIVE AND ELIGIBLE FOR ART AT SELECTED AGES

(effect of COTRIMOXAZOLE [TMP-SMX] prophylaxis and/or ART for symptomatic)

0

10,000

20,000

30,000

40,000

50,000

60,000

Age 1 Age 2 Age 5 Age 10

no TMP, no ARV

with ARV, no TMP

with TMP. No ARV

Marie-Louise Newell, Kirsty Little, Madeleine Bunders (Ghent-IAS Group on HIV infection in women and children)

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)

171106

0

100,000

200,000

300,000

Age 1 Age 2 Age 5 Age 10

with TMP. No ARV

ALIVE 100% CTX

Marie-Louise Newell, Kirsty Little, Madeleine Bunders (Ghent-IAS Group on HIV infection in women and children)

ARV liquid formulations can become expensive ..

Regimen PaediatricCost

per month

Cost Per

monthCost per

dayCost

per dayTotal

generic* CostsTotal

Branded Costs

  original generic original generic 1 yr 5 yrs 1 yr 5 yrs

ZDV+3TC+NVP*

(<3yrs/10kg) 54.83 15.62 1.83 0.52 185.30 926 650.64 3,253

ZDV+3TC+NVP*

(>3yrs/20kg) 113.92 38.38 3.80 1.28 455.42 2,277 1351.83 6,759

d4T*+3TC+NVP*

(<3yrs/10kg) 42.36 11.97 1.41 0.40 142.04 710 502.68 2,513

d4T*+3TC+NVP*

(>3yrs/20kg) 86.14 81.39 23.44 0.78 278.18 1,391 1022.20 5,111

ZDV+3TC+EFV* (10kg with liquid) 44.53 37.34 1.48 1.24 443.13 2,216 528.39 2,642

ZDV+3TC+EFV* (10kg with tab) 32.98 25.79 1.10 0.86 306.07 1,530 391.33 1,957

ZDV+3TC+EFV* (20kg with liquid) 85.76 58.41 2.86 1.95 603.15 3,466 1017.65 5,088

ZDV+3TC+EFV* (20kg with tab) 72.67 45.32 2.42 1.51 537.82 2,689 862.32 4,312

ZDV+3TC+ABC*

(<3yrs/10kg) 62.49 49.10 2.08 1.64 582.59 2,913 741.56 3,708

* no generic                        

Note: calculations based on 10kg and 20kg scenarios    

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 $16Best innovator price/y $ 508 $27.24

• Managing the switch – increases complexities in resource poor settings

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

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 …..