Andrew F. Auld, Omotayo Bolu, Tracy Creek, Mary Lou Lindegren,

1

Potential Impact and Cost-Effectiveness of the 2009 “Rapid Advice” PMTCT Guidelines

— 15 Resource-Limited Countries, 2010

Andrew F. Auld, Omotayo Bolu, Tracy Creek, Mary Lou Lindegren, Emilia Rivadeneira, Helen Dale, Nalinee Sangrujee, Tedd Ellerbrock

Global AIDS Program, Centers for Disease Control and Prevention (CDC), Atlanta, U.S.A

Presented by Andrew F. Auld MBChB

2

Peri-natal HIV Transmission

• Globally, 420,000 infants become HIV-infected annually

• About 90% of infections occur in Africa 60% during pregnancy/birth 40% during breastfeeding

• Antiretroviral drugs (ARVs) known to significantly reduce HIV transmission during pregnancy and birth In 2009 ARVs proven effective during breastfeeding

• Guidelines for the use of ARVs for prevention of mother-to-child transmission (PMTCT): Last published in 2006 Revised in 2009

2006 vs. 2009 WHO PMTCT Guidelines -ART-Ineligible Women Choosing to Breastfeed

2006 PMTCT Guidelines


Option A Option B

Mother

Pregnancy AZT from 28 weeks AZT from 14 weeks

Triple ARV14 weeks –>

end of Breastfeeding

Delivery SDN + AZT-3TC SDN + AZT-3TC

Post-Natal AZT-3TC tail AZT-3TC tail

Infant Post-Natal SDN & AZT tail Daily NVP during BF NVP for 6 weeks

3




Option A Option B

Mother







4




Option A Option B

Mother







5




Option A Option B

Mother







6




Option A Option B

Mother







7




Option A Option B

Mother







8




Option A Option B

Mother







9

Earlier ART for HIV-Infected Pregnant Women

• 2006 WHO Guidelines:

CD4 < 200/µL

CD4 < 350/µL with WHO stage III

All WHO stage IV eligible

• 2009 WHO Guidelines: Earlier ART

CD4 < 350/µL

All WHO stage III/IV eligible10

11

Rationale & Objectives for Research

• Rationale:

2009 PMTCT guidelines, adopting options A or B for ART-ineligible women, equally effective for HIV prevention (WHO 2009)

Other criteria, e.g. cost-effectiveness, feasibility, are important

• Objectives:

To estimate in 15 resource-limited countries:

- the potential cost-effectiveness

- the potential costs saved, through reduced need to treat HIV-infected children,

if countries choose option A or option B

12

15 Focus Countries of the US President’s Emergency Plan for AIDS Relief

EthiopiaUganda

KenyaRwandaTanzaniaZambiaMozambique

Haiti

Guyana

Cote d’Ivoire

Nigeria

NamibiaBotswana

South Africa

Vietnam

13

Methods

• Deterministic model:

Follow cohorts of HIV-infected pregnant women and exposed infants born in each of the 15 focus countries during 2010

Three PMTCT scenarios:

- Scenario “A”: 2009 Guidelines with option A for ART-ineligible women

- Scenario “B”: 2009 Guidelines with option B for ART-ineligible women using the least expensive prophylactic regimen (AZT,3TC,EFV)

- Scenario “2006”: 2006 WHO Guidelines

14

Methods

• To estimate cost-effectiveness of scenarios “A” & “B”, estimate:

Incremental cost-effectiveness ratios (ICERs)

- Additional cost per additional life-years gained (LYG) of implementing either scenario “A” or “B” instead of the 2006 Guidelines

• If ICER < Gross Domestic Product (GDP) / Capita:

Highly Cost-effective

15

Methods

• To estimate whether scenarios A & B are cost saving, estimate for each of the scenarios (“A”, “B”, and “2006”):

Total costs incurred by PMTCT program

Total lifetime treatment costs for infected children

• If total costs for scenario A or B < total costs for scenario 2006:

Cost-saving

16

Assumptions and Sensitivity Analysis

• Key input parameters:

PMTCT effectiveness data: Kesho-Bora and Ban

ARV costs and service fees: ARV procurement agencies & costing surveys

• Multivariate sensitivity analysis:

10,000 trials of Monte Carlo simulation created 95% confidence intervals (CI)

Potential Impact and Cost-Effectiveness of Scenarios “A” and “B” of the 2009 PMTCT Guidelines – 15 Focus Countries, 2010

17

Model Outcome Scenario “2006” (95% CI)

Scenario “A”(95% CI)

Scenario “B”(95% CI)

Infant HIV Infections(thousands) 345 (328-361) 242 (231-252) 258 (247-270)

Infections Averted (thousands) 66 (50-82) 169 (159-180) 152 (141-163)

Life-Years Gained (LYG millions) 1.3 (0.7-2.0) 3.2 (2.7-3.6) 2.9 (2.4-3.4)

Additional LYG (millions) - 1.9 (0.8-2.9) 1.6 (0.4-2.7)

Cost (US $ millions) 64 (55-73) 235 (223-247) 343 (325-362)

Additional Cost(millions) - 171 (150-192) 288 (252-307)

ICER (US $/LYG) - 92 (81-107) Equally Effective

More Expensive


18








Cost (US $ millions) 64 (55-73) 235 (223-247) 343 (325-362)



More Expensive


19








Cost (US $ millions) 64 (55-73) 235 (223-247) 343 (325-362)



More Expensive


20








Cost (US $ millions) 64 (55-73) 235 (223-247) 343 (325-362)



More Expensive


21








Cost (US $ millions) 64 (55-73) 235 (223-247) 343 (325-362)



More Expensive


22








Cost (US $ millions) 64 (55-73) 235 (223-247) 343 (325-362)



More Expensive


23








Cost (US $ millions) 64 (55-73) 235 (223-247) 343 (325-362)



More Expensive


24








Cost (US $ millions) 64 (55-73) 235 (223-247) 343 (325-362)



More Expensive


25








Cost (US $ millions) 64 (55-73) 235 (223-247) 343 (325-362)



More Expensive


26








Cost (US $ millions) 64 (55-73) 235 (223-247) 343 (325-362)



More Expensive


27








Cost (US $ millions) 64 (55-73) 235 (223-247) 343 (325-362)



More Expensive


28








Cost (US $ millions) 64 (55-73) 235 (223-247) 343 (325-362)



More Expensive


29








Cost (US $ millions) 64 (55-73) 235 (223-247) 343 (325-362)



More Expensive

Average ICER of implementing Scenario “A” Instead of Scenario “2006” – 15 Focus Countries, 2010

30

Threshold for High Cost Effectiveness (Weighted Average GDP - US$1,463)

Point Estimate for ICER of Scenario A vs. 2006 WHO PMTCT Guidelines (US$92)

10,000 Trials of Monte Carlo Simulationfor ICER of Scenario A vs. 2006 WHO Guidelines

050

100

150

200

Add

ition

al P

MTC

T A

RV

Del

iver

y E

xpen

ditu

re (m

illio

ns U

S$)

0 .5 1 1.5 2 2.5Additional Life-Years Gained (millions)


31




050

100

150

200

Add

ition

al P

MTC

T A

RV

Del

iver

y E

xpen

ditu

re (m

illio

ns U

S$)



32




050

100

150

200

Add

ition

al P

MTC

T A

RV

Del

iver

y E

xpen

ditu

re (m

illio

ns U

S$)



33




050

100

150

200

Add

ition

al P

MTC

T A

RV

Del

iver

y E

xpen

ditu

re (m

illio

ns U

S$)


Country-Specific ICERs of Implementing Scenario “A” Instead of Scenario “2006” – 15 Focus Countries, 2010

34

Rw

anda

Zam

bia

Uga

nda

Nig

eria

Moz

ambi

que

Tanz

ania

Eth

iopi

a

Bot

swan

a

Cot

e d'

Ivoi

re

Ken

ya

Sou

th A

frica

Hai

ti

Nam

ibia

Guy

ana

Vie

tnam

$0.00

$20.00

$40.00

$60.00

$80.00

$100.00

$120.00

$140.00

0.0%

5.0%

10.0%

15.0%

20.0%

25.0%

30.0%ICER Scenario "A" vs. 2006 WHO GuidelinesICER as a % of Country-Specific GDP per Capita

Incr

emen

tal C

ost-E

ffect

iven

ess

Rat

io (I

CER

) US$

ICER

as

a Pe

rcen

tage

of t

he C

ount

ry's

GDP

per

Cap

ita


35

Rw

anda

Zam

bia

Uga

nda

Nig

eria

Moz

ambi

que

Tanz

ania

Eth

iopi

a

Bot

swan

a

Cot

e d'

Ivoi

re

Ken

ya

Sou

th A

frica

Hai

ti

Nam

ibia

Guy

ana

Vie

tnam

$0.00

$20.00

$40.00

$60.00

$80.00

$100.00

$120.00

$140.00

0.0%

5.0%

10.0%

15.0%

20.0%

25.0%

30.0%$115 ICER Scenario "A" vs. 2006 WHO GuidelinesICER as a % of Country-Specific GDP per Capita

Incr

emen

tal C

ost-E

ffect

iven

ess

Rat

io (I

CER

) US$

ICER

as

a Pe

rcen

tage

of t

he C

ount

ry's

GDP

per

Cap

ita


36

Rw

anda

Zam

bia

Uga

nda

Nig

eria

Moz

ambi

que

Tanz

ania

Eth

iopi

a

Bot

swan

a

Cot

e d'

Ivoi

re

Ken

ya

Sou

th A

frica

Hai

ti

Nam

ibia

Guy

ana

Vie

tnam

$0.00

$20.00

$40.00

$60.00

$80.00

$100.00

$120.00

$140.00

0.0%

5.0%

10.0%

15.0%

20.0%

25.0%

30.0%$115

$70

ICER Scenario "A" vs. 2006 WHO GuidelinesICER as a % of Country-Specific GDP per Capita

Incr

emen

tal C

ost-E

ffect

iven

ess

Rat

io (I

CER

) US$

ICER

as

a Pe

rcen

tage

of t

he C

ount

ry's

GDP

per

Cap

ita


37

Rw

anda

Zam

bia

Uga

nda

Nig

eria

Moz

ambi

que

Tanz

ania

Eth

iopi

a

Bot

swan

a

Cot

e d'

Ivoi

re

Ken

ya

Sou

th A

frica

Hai

ti

Nam

ibia

Guy

ana

Vie

tnam

$0.00

$20.00

$40.00

$60.00

$80.00

$100.00

$120.00

$140.00

0.0%

5.0%

10.0%

15.0%

20.0%

25.0%

30.0%ICER Scenario "A" vs. 2006 WHO GuidelinesICER as a % of Country-Specific GDP per Capita

Incr

emen

tal C

ost-E

ffect

iven

ess

Rat

io (I

CER

) US$

ICER

as

a Pe

rcen

tage

of t

he C

ount

ry's

GDP

per

Cap

itaEthiopia ICER US $94GDP per capita ~US $364

Potential Cost Savings of Implementing PMTCT Scenario “A” Instead of the 2006 PMTCT Guidelines

38

Tan

zani

a

Zam

bia

Nig

eria

Cot

e d'

Ivoi

re

Vie

tnam Hai

ti

Guy

ana

Nam

ibia

$(30.0)

$(25.0)

$(20.0)

$(15.0)

$(10.0)

$(5.0)

$-

$5.0

$10.0

$15.0

$20.0

Diff

eren

ce in

Com

bine

d C

osts

for P

MTC

T &

Ped

iatri

c Tr

eatm

ent

(US$

mill

ions

)

Sou

th A

frica

Ken

yaUga

nda

Bots

wan

a

Moz

ambi

que

Eth

iopi

a

Rw

anda


39

Tan

zani

a

Zam

bia

Nig

eria

Cot

e d'

Ivoi

re

Vie

tnam Hai

ti

Guy

ana

Nam

ibia

$(30.0)

$(25.0)

$(20.0)

$(15.0)

$(10.0)

$(5.0)

$-

$5.0

$10.0

$15.0

$20.0

Diff

eren

ce in

Com

bine

d C

osts

for P

MTC

T &

Ped

iatri

c Tr

eatm

ent

(US$

mill

ions

)

Sou

th A

fric

a

Keny

a

Uga

nda

Bot

swan

a

Moz

ambi

que

Eth

iopi

a

Rw

anda


40

Tan

zani

a

Zam

bia

Nig

eria

Cot

e d'

Ivoi

re

Vie

tnam Hai

ti

Guy

ana

Nam

ibia

$(30.0)

$(25.0)

$(20.0)

$(15.0)

$(10.0)

$(5.0)

$-

$5.0

$10.0

$15.0

$20.0

Diff

eren

ce in

Com

bine

d C

osts

for P

MTC

T &

Ped

iatri

c Tr

eatm

ent

(US$

mill

ions

)

Sou

th A

frica

Ken

yaUga

nda

Bots

wan

a

Moz

ambi

que

Eth

iopi

a

Rw

anda


41

Tan

zani

a

Zam

bia

Nig

eria

Cot

e d'

Ivoi

re

Vie

tnam Hai

ti

Guy

ana

Nam

ibia

$(30.0)

$(25.0)

$(20.0)

$(15.0)

$(10.0)

$(5.0)

$-

$5.0

$10.0

$15.0

$20.0

Diff

eren

ce in

Com

bine

d C

osts

for P

MTC

T &

Ped

iatri

c Tr

eatm

ent

(US$

mill

ions

)

Sou

th A

frica

Ken

yaUga

nda

Bots

wan

a

Moz

ambi

que

Eth

iopi

a

Rw

anda


42

Tan

zani

a

Zam

bia

Nig

eria

Cot

e d'

Ivoi

re

Vie

tnam Hai

ti

Guy

ana

Nam

ibia

$(30.0)

$(25.0)

$(20.0)

$(15.0)

$(10.0)

$(5.0)

$-

$5.0

$10.0

$15.0

$20.0

Diff

eren

ce in

Com

bine

d C

osts

for P

MTC

T &

Ped

iatri

c Tr

eatm

ent

(US$

mill

ions

)

Sou

th A

frica

Ken

yaUga

nda

Bots

wan

a

Moz

ambi

que

Eth

iopi

a

Rw

anda

Total Cost Savings of US$ 18 million

95% CI (US$ 49 million in savings – US$ 68 million in additional expenditure)

43

Limitations

• In establishing 95% CIs, only those input parameters that affected the ICER were varied

• Costs of ARVs are continually changing

44

Public Health Implications

• In 2010, in 15 PEPFAR focus countries, we estimate:

Implementing 2009 WHO Guidelines could nearly triple infections averted

Option “B” is significantly more expensive than option “A”

The 2009 WHO Guidelines with option “A” are:

- highly cost effective

- possibly cost-saving in 9 of 15 PEPFAR focus countries

45

Public Health Implications

• These findings support:

Rapid implementation of the 2009 WHO PMTCT Guidelines

Option “A” the most cost-effective option

Acknowledgements

• Co-authors

• Omotayo Bolu

• Tracy Creek

• Mary Lou Lindegren

• Emilia Rivadeneira

• Helen Dale

• Nalinee Sangrujee

• Tedd Ellerbrock

• Collaborators

• Ray Shiraishi

• Elliot Raizes

• David Bell

• Nick Menzies

• Prahbu Vimanaland

• John Blandford

Thank You!

The findings of this presentation are those of the authors and do not necessarily represent the views of the US Centers for

Disease Control and Prevention

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Mother-to-Child HIV-Infections among Exposed Children Born in 15 Focus Countries, 2010

48

Nig

eria

Sou

th A

frica

Ken

ya

Tan

zani

a

Moz

ambi

que

Eth

iopi

a

Zam

bia

Uga

nda

Cot

e d'

Ivoi

re

Rw

anda

Bot

swan

a

Nam

ibia

Vie

tnam Hai

ti

0

10,000

20,000

30,000

40,000

50,000

60,000

70,000

80,000

2006 Guidelines - Scenario "2006"

2009 Guidelines - Scenario "A"

2009 Guidelines - Scenario "B"

Num

ber o

f Mot

her t

o C

hild

HIV

Infe

ctio

ns

Guy

ana

: Total Infections ~ 345,000



Life-Time Treatment Costs for Infected Children Associated with PMTCT Strategy – 15 Focus Countries, 2010

49

Sou

th A

frica

Ken

ya

Uga

nda

Moz

ambi

que

Nig

eria

Eth

iopi

a

Zam

bia

Tan

zani

a

Bot

swan

a

Rw

anda

Cot

e d'

Ivoi

re

Nam

ibia

Hai

ti

Vie

tnam

Guy

ana

$-

$20.0

$40.0

$60.0

$80.0

$100.0

$120.0

Scenario "2006"

Scenario "A"

Life

-Tim

e Tr

eatm

ent C

osts

for I

nfec

ted

Chi

ldre

n (U

S$ m

illio

ns)

: Total Treatment Costs ~US$ 440 million

: Total Treatment Costs ~US$ 251 million

Varying Costs and Effectiveness of PMTCT Scenario “A” to Assess Effect on ICER – Ethiopia, 2010

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Ris

k E

stim

ate

1.5

X ri

sk

2 X

risk

2.5

X ri

sk

3 X

risk

3.5

X ri

sk

4 X

risk

4.5

X ri

sk

5 X

risk

$0

$500

$1,000

$1,500

$2,000

$2,500

$3,000

$3,500

$4,000

$4,500

Cost Estimate

5 X Cost

20 X Cost

GDP per Capita

3 X GDP per Capita

Increase in Transmission Risk Above Model Estimate

ICER

(US$

per

add

ition

al L

YG)

Andrew F. Auld, Omotayo Bolu, Tracy Creek, Mary Lou Lindegren,

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