access to paediatric arv formulations the plight of children

January 2006Access to Paediatric ARV formulations

Access to Paediatric ARV Formulations

The plight of Children


UNICEF SUPPLY DIVISIONARV formulations available …………

Product portfolio include:

• ARVS 42 formulations in 75 different presentations,

30 - 40% can be used for children

• HIV tests, CD4, CD8, Viral load including • PCR equipment ( 2 suppliers )


Access to paediatric ARV formulations depends on effective supply chain management

Demand

SupplierAgreements

FinancingReceipt, Storage,

Distribution

Forecasting

QualityAssurance

EffectiveUse

ProductProcurement

ProductSelection

Monitoring


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


FIRST LINE / PMTCT:ARV Formulations available...

Treatment Products available Price (US $ / 100ml)

PMTCT/ 1st Line Innovator Generic Innovator * Generic #

D4T Yes Yes0.75

4.23 – 18.66 1.50

ZDV Yes Yes3.55

2.961.45

1.53 - 2.10

3TC Yes Yes 2.801.20

1.68 - 2.00

NVP Yes Yes 7.29

8.751.20

2.00 - 2.45EFV 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

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


PRODUCT SELECTION : When to start ; What to start with ….

• For Prevention of Mother to Child Transmission:

For infant:

Nevirapine (NVP) single dose 0,6mlZidovudine (ZDV) 4mg/kg 2x daily, for 1 weekLamivudine (3TC) 2mg/kg 2x daily, for 1 week

See http://www.who.int/hiv/pub/mtct/guidelines/en/


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 No10.66

9.64

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


FORECASTING : When to start ; What to start with ….

• For Treatment and Care: First Line

Variations ofZidovudine (ZDV) < 4 weeks: 4mg/kg 2x daily

4 wks – 13 years: 180mg/m2/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/kg30 days – 13 years: 120mg/m2/dose once a dayfor 2 weeks, then 120-200mg/m2/dose 2x daily

Efavirenz (EFV) Only > 3 years, > 10kg


FORECASTING : When to start ; What to start with ….

• For Treatment and Care: Second Line

Variations ofAbacavir (ABC) < 16yrs or < 37,5kg: 8mg/kg 2x daily

Didanosine (ddI) < 3 months : 50mg/m2/dose 2x daily3 months – 13 yrs : 90-120 mg/m2/dose 2x daily, or 240mg/m2/dose once a day

Lopinavir/ritonavir 6 months – 13 years: 225mg/m2 LPV, plus(LPV/r) 57,5 mg/m2 ritonavir 2x daily, or weight based

Nelfinavir (NFV) < 1 yr: 50mg/kg/dose 3x daily, or 75mg/kg/dose bd1 yr - 13 yrs: 55 – 65 mg/kg/dose 2x daily


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 ? 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 …

Access to Paediatric ARV formulationsJanuary 2006

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



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



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 43.43 1.83 1.45 515.35 2,577 650.64 3,253

ZDV+3TC+NVP*

(>3yrs/20kg) 113.92 92.65 3.80 3.09 1099.50 5,498 1351.83 6,759

d4T*+3TC+NVP*

(<3yrs/10kg) 42.36 39.78 1.41 1.33 472.10 2,361 502.68 2,513

d4T*+3TC+NVP*

(>3yrs/20kg) 86.14 81.39 2.87 2.71 965.87 4,829 1022.20 5,111

ZDV+3TC+EFV* (10kg with liquid) 44.53 39.34 1.48 1.31 466.81 2,334 528.39 2,642

ZDV+3TC+EFV* (10kg with tab) 32.98 27.79 1.10 0.93 329.75 1,649 391.33 1,957

ZDV+3TC+EFV* (20kg with liquid) 85.76 62.09 2.86 2.07 736.76 3,684 1017.65 5,088

ZDV+3TC+EFV* (20kg with tab) 72.67 49.00 2.42 1.63 581.43 2,907 862.32 4,312

ZDV+3TC+ABC*

(<3yrs/10kg) 62.49 51.09 2.08 1.70 606.27 3,031 741.56 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 …..



Demand

SupplierAgreements


Distribution

Forecasting

QualityAssurance

EffectiveUse

ProductProcurement

ProductSelection

Monitoring



DemandCreation

SupplierAgreements


Distribution

Forecasting

QualityAssurance

EffectiveUse

ProductProcurement

ProductSelection

Monitoring

Calculating

the number

of bottles we should/can buy …

We need partners

to complete the cycle

access to paediatric arv formulations the plight of children

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