Transcript Powerpoint

Scaling up antiretroviral therapy
in resource poor countries:
The impact of speed on survival
Rochelle P. Walensky, MD, MPH
Associate Professor of Medicine
Harvard Medical School
Divisions of Infectious Disease
Massachusetts General Hospital
Brigham and Women’s Hospital
Supported by NIAID, NIMH, and
Doris Duke Charitable Foundation
PEPfAR Reauthorized
July 2008
• $48 billion
• Is this too much? Not enough?
• How can we measure the value
when dollars are spent?
Overview
• Methods of cost-effectiveness analysis
• What is the value of :
– Antiretroviral therapy (Côte d’Ivoire)?
– Second-line therapy (India)?
– Earlier treatment initiation (South Africa)?
• What is the projected impact of PEPfAR
funding over the next 5 years?
Cost-effectiveness:
Common Misconceptions
“Cost-Effective” = “Cheap”
“Cost-Effective” = “Saves Money”
“Cost-Effective” = Additional benefit worth the
additional cost ($/YLS)
Cost-effectiveness is about
Value for Money
• Two different outcome measures
– Cost in dollars
– Effectiveness: years of life saved (YLS)
quality-adjusted life years
(QALYs)
• Cost-effectiveness ratio:
Additional Resource Use ($)
Additional Health Benefits (YLS)
Cost-effectiveness of Preventing AIDS
Complications (CEPAC)-International
•
•
•
CEPAC is a simulation model of HIV disease and
treatment that incorporates CD4 count, HIV RNA,
ART, OIs
Clinical data are from Côte d’Ivoire, India, and South
Africa
Model provides outcomes measured in:
–
–
–
•
Mean projected life expectancy
1-, 5-, 10-yr morbidity and mortality
Mean projected per person costs
Designed to address the most critical questions in
resource-limited settings
Funded by NIAID/NIMH/DDCF
Methods:
Cost-effectiveness Thresholds
The Commission on Macroeconomics and Health of
the WHO have suggested that interventions are:
• Very cost-effective: the CE ratio is <1X Gross
Domestic Product (GDP) per capita for that country
– $803 for Côte d’Ivoire
– $590 for India
– $5,300 for South Africa
– $43,000 for US
• Cost-effective: the CE ratio is
<3 x GDP per capita for that country
Macroeconomics and Health: WHO 2001
Data from Côte d’Ivoire
• Collaborators: Xavier Anglaret, MD, PhD,
ANRS 059
• Mean age 33 yr, 40% male
• Mean CD4 count 331/µl
• ART 52-week efficacy/annual cost:
– First-line (NNRTI): 51% suppression, $292/yr
Model Validation:
Data from Côte d’Ivoire
Ot her S
Ot her M
MAC
ANRS 059 Trial
Model
Toxo
Isosp
Malaria
[ S: Severe, M: Mild]
TB
Fungal S
Fungal M
Bact S
Bact M
0
0.05
0.1
0.15
0.2
Cumulative Incidence
0.25
0.3
0.35
Goldie et al NEJM 2006
Cost-effectiveness of ART:
Côte d’Ivoire
Strategy
ART Start
Criteria
ART
Stop
Criteria
Life
Expectancy
(mo)
Costs
($)
C-E Ratio
($/yr life
saved)
--
--
--
31.4
780
--
T/S alone
No
--
--
32.8
810
240
T/S + ART
No
2 ODs
1 OD
41.4
1,230
590
T/S + ART
No
1 OD
1 OD
50.7
1,720
620
T/S + ART
No
1 OD
3 ODs
56.8
2,170
890
T/S + ART
No
1 OD
5 ODs
57.9
2,260
1,060
T/S + ART
Yes
CD4<200,
CD4<350 and 1
severe OD,
or 1 OD
90%
in CD4
count
69.6
3,420
1,180
No Treatment
GDP: $803
CD4
Test
Goldie et al NEJM 2006
But what about expensive
second-line therapy?
Data from India
•
•
•
•
YRG Care, N. Kumarasamy, MD
Mean age: 32.6 yr, 66% male
Mean CD4 count: 318/µl
ART 48-week efficacy/annual cost:
– First-line (NNRTI): 55% suppression, $222/yr
– Second-line (PI): 65% suppression, $1,435/yr
The value of two lines of ART:
India
Strategy
No treatment
One line ART (NNRTI)
(<200/µl)
Two lines ART (NNRTI/PI)
(<200/µl)
Lifetime
cost ($)*
580
Survival
(months)
C-E Ratio
($/YLS)
35.9
--
1,540
62.4
450
4,980
84.8
1,850
GDP: $590 *All costs in 2005 US$, converted using GDP deflators
& the mean exchange rate between the Rupee & US$
Freedberg et al., AIDS 2007, World Bank
When to Start?
• The question of “when to start” ART has drawn
interest globally
• In resource-limited settings, this question is crucial:
– Limited available ART regimens
– Increased incidence of opportunistic infections (OIs) and
tuberculosis (TB) at higher CD4 counts
• A clinical trial may be well-suited to address the
“when to start” question
• Results from such a trial will not be available for at
least 5 years; two trials are currently enrolling
Data from South Africa
• CTAC/Gugulethu Cohorts
– Robin Wood, FCP, MMed, DTM&H, U CapeTown
• Mean age 33 yr, 55% male
• Mean CD4 count 375/µl
• ART 48-week efficacy/annual cost:
– First-line (NNRTI): 84% suppression, $288/yr
– Second-line (PI): 71% suppression, $564/yr
“When to Start” ART:
South Africa
Strategy
Survival
(years)
3.83
C-E Ratio
($/YLS)
--
Deferred ART (<250/µl or OI) 10,820
10.33
1,110
Earlier ART (<350/µl or OI)
11.03
1,200
No treatment
Lifetime
cost ($)*
3,620
11,660
GDP: $5,300 *All costs in 2006 US$, converted using GDP
deflators & the mean exchange rate between the
SA Rand & US$
Walensky et al CROI 2008 [abstract]
Proportion Alive
Results:
Proportion Alive at 5 Years
1
Earlier ART
0.9
Deferred ART
0.8
0.7
No ART
0.6
0.5
0
1
2
3
4
5
Time (Years)
Walensky et al CROI 2008 [abstract]
ART Roll Out:
The impact of speed on survival
Alternative ART rollout scenarios in South Africa
OR what might more PEPFAR funds mean?
1) To forecast
– Number of lives lost awaiting therapy
– Number of patients in treatment
2) To project when total ART need would be met
3) To inform decisions regarding the life-saving
value of alternative treatment expansion
scenarios
4 Growth Scenarios
New ART Slots
by 2012
Source
Zero growth
100,000
---
Constant growth
600,000
ASSA
Moderate growth
2,100,000
SA Joint Task Team
Rapid growth
2,400,000
---
Walensky et al., JID 2008
Percent ART Need Met by Year
Rapid
100%
% ART Need Met
90%
80%
Moderate
70%
60%
Constant
50%
40%
Zero
30%
20%
10%
0%
2007
2008
2009
2010
2011
2012
Year
Walensky et al., JID 2008
Projected Deaths and
Patients Alive on ART: 2007-2012
AIDS Deaths
Alive on ART
Zero growth
2,465,000
1,290,000
Constant growth
2,160,000
1,595,000
Moderate growth
1,449,000
2,306,000
Rapid growth
1,232,000
2,523,000
Walensky et al., JID 2008
Impact of No CD4 Monitoring
on Deaths
Decisions on treatment initiation and switching based
on clinical criteria
CD4
No CD4
Increased
Monitoring Monitoring Deaths
Zero growth
2,465,000
2,568,000
103,000
Constant growth
2,160,000
2,436,000
276,000
Moderate growth
1,449,000
2,237,000
788,000
Rapid growth
1,232,000
2,218,000
986,000
Walensky et al JID 2008
Timeline of Major HIV
Interventions
ART 4
ART 3
ART 2
ART 1
pMTCT - AZT
ZDV
MAC Prophylaxis
pMTCT - ART
PCP Prophylaxis
89 990 991 992 993 994 995 996 997 998 999 000 001 002 003
9
1
1
1
1
1
1
1
1
1
1
1
2
2
2
2
Walensky et al., JID 2006
AIDS Survival by Era
100%
Untreated HIV/AIDS
% Alive
90%
1989 - PCP
80%
1993 - PCP/MAC
70%
1996 - PCP/MAC + ART 1
1998 - PCP/MAC + ART 2
60%
2000 - PCP/MAC + ART 3
50%
2003 - PCP/MAC + ART 4
40%
30%
20%
10%
0%
0
5
10
15
20
25
30
Years from treatment start
35
40
Walensky et al., JID 2006
Future Directions
• What are the next most important questions?
• The clinical and economic value of CD4
and/or HIV RNA laboratory monitoring?
• The cost-effectiveness of genotype testing?
• The clinical and economic impact of routine
HIV screening?
• Which of these results are country-specific?
Which are generalizable around the globe?
Conclusions
• In resource-limited settings, quantitative
assessments of value for money are critical,
given multiple treatment strategies.
• Cost-effectiveness analyses have
demonstrated the value of 1st and 2nd-line
therapy, of earlier ART initiation, and of the
need for increasingly rapid ART roll-out in
international settings.
• HIV simulation modeling is a powerful tool to
inform health policy and to understand
survival, costs and cost-effectiveness of
alternative clinical interventions.
CEPAC (and other) Investigators: US
Harvard Medical School
Harvard SPH
Ingrid Bassett, MD, MPH
Melissa Bender, MD, MPH
Sarah Chung
John Chiosi
Andrea Ciaranello, MD
Kenneth Freedberg, MD, MSc
Louise Ivers, MD
Elena Losina, PhD
Ben Linas, MD, MPH
Zhigang Lu, MD
Brandon Morris
Paul Sax, MD
Caroline Sloan
Heather Smith
Lauren Uhler
Rochelle Walensky, MD, MPH
Bingxia Wang, PhD
Sue Goldie, MD, MPH
Kara Cotich
Callie Scott
George Seage, III DSc, MPH
Milton Weinstein, PhD
April Kimmel, MSc
Cornell
Bruce Schackman, PhD, MBA
Yale
David Paltiel, PhD
Lille, France
Yazdan Yazdanpanah, MD, PhD
CEPAC Investigators: International
Côte d’Ivoire
OECS
Xavier Anglaret, MD, PhD
Eugene Messou, MD
Catherine Seyler, MD, PhD
Siaka Touré, MD, MPH
Kathleen Allen-Ferdinand, MD
Paul Ricketts, MD
Hazel Williams-Roberts, MD
South Africa
India
N. Kumarasamy, MBBS, PhD
Tim Flanigan, MD
Kenneth Mayer, MD
Neil Martinson, MBBCh, MPH
James McIntyre, MBChB,MRCOG
Lerato Mohapi, MBBCH
Robin Wood, MD