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
Is this too much? Not enough?
How can we measure the value when dollars are spent?
PEPfAR Reauthorized July 2008
Methods of cost-effectiveness analysis
What is the value of :
Antiretroviral therapy (C ô te 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 ($/YLS)
Cost-effectiveness is about Value for Money
Two different outcome measures
Cost in dollars
Effectiveness: years of life saved (YLS)
quality-adjusted life years (QALYs)
Additional Resource Use ($)
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 C ô te 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 C ô te 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 C ô te d’Ivoire Cumulative Incidence Goldie et al NEJM 2006
Cost-effectiveness of ART: C ô te d’Ivoire Goldie et al NEJM 2006 GDP: $803 -- 780 31.4 -- -- -- No Treatment 1,180 3,420 69.6 90% in CD4 count CD4<200, CD4<350 and 1 severe OD, or 1 OD Yes T/S + ART 1,060 2,260 57.9 5 ODs 1 OD No T/S + ART 890 2,170 56.8 3 ODs 1 OD No T/S + ART 620 1,720 50.7 1 OD 1 OD No T/S + ART 590 1,230 41.4 1 OD 2 ODs No T/S + ART 240 810 32.8 -- -- No T/S alone C-E Ratio ($/yr life saved) Costs ($) Life Expectancy (mo) ART Stop Criteria ART Start Criteria CD4 Test Strategy
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, $1,435/yr
The value of two lines of ART: India *All costs in 2005 US$, converted using GDP deflators & the mean exchange rate between the Rupee & US$ Freedberg et al., AIDS 2007, World Bank GDP: $590 1,850 84.8 4,980 Two lines ART (NNRTI/PI) (<200/ µl) 450 62.4 1,540 One line ART (NNRTI) (<200/ µl) -- 35.9 580 No treatment C-E Ratio ($/YLS) Survival (months) Lifetime cost ($)* Strategy
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
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, $564/yr
“ When to Start” ART: South Africa *All costs in 2006 US$, converted using GDP deflators & the mean exchange rate between the SA Rand & US$ Walensky et al CROI 2008 [abstract] GDP: $5,300 1,200 11.03 11,660 Earlier ART (<350/ µl or OI) 1,110 10.33 10,820 Deferred ART (<250/ µl or OI) -- 3.83 3,620 No treatment C-E Ratio ($/YLS) Survival (years) Lifetimecost ($)* Strategy
Results: Proportion Alive at 5 Years Deferred ART Earlier ART No ART 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?
Number of lives lost awaiting therapy
Number of patients in treatment
To project when total ART need would be met
To inform decisions regarding the life-saving value of alternative treatment expansion scenarios
4 Growth Scenarios Walensky et al., JID 2008 --- 2,400,000 Rapid growth SA Joint Task Team 2,100,000 Moderate growth ASSA 600,000 Constant growth --- 100,000 Zero growth Source New ART Slots by 2012
Percent ART Need Met by Year Rapid Moderate Constant Zero Year % ART Need Met Walensky et al., JID 2008
Projected Deaths and Patients Alive on ART: 2007-2012 Walensky et al., JID 2008 2,523,000 1,232,000 Rapid growth 2,306,000 1,449,000 Moderate growth 1,595,000 2,160,000 Constant growth 1,290,000 2,465,000 Zero growth Alive on ART AIDS Deaths
Impact of No CD4 Monitoring on Deaths Decisions on treatment initiation and switching based on clinical criteria Walensky et al JID 2008 2,218,000 2,237,000 2,436,000 2,568,000 No CD4 Monitoring 986,000 1,232,000 Rapid growth 788,000 1,449,000 Moderate growth 276,000 2,160,000 Constant growth 103,000 2,465,000 Zero growth Increased Deaths CD4 Monitoring
Timeline of Major HIV Interventions Walensky et al., JID 2006
AIDS Survival by Era Walensky et al., JID 2006
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?
In resource-limited settings, quantitative assessments of value for money are critical, given multiple treatment strategies.
Cost-effectiveness analyses have demonstrated the value of 1 st and 2 nd -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
Ingrid Bassett, MD, MPH
Melissa Bender, MD, MPH
Andrea Ciaranello, MD
Kenneth Freedberg, MD, MSc
Louise Ivers, MD
Elena Losina, PhD
Ben Linas, MD, MPH
Zhigang Lu, MD
Paul Sax, MD
Rochelle Walensky, MD, MPH
Bingxia Wang, PhD
Sue Goldie, MD, MPH
George Seage, III DSc, MPH
Milton Weinstein, PhD
April Kimmel, MSc
Bruce Schackman, PhD, MBA
David Paltiel, PhD
Yazdan Yazdanpanah, MD, PhD
CEPAC Investigators: International
C ô te d’Ivoire
Xavier Anglaret, MD, PhD
Eugene Messou, MD
Catherine Seyler, MD, PhD
Siaka Tour é , MD, MPH
Neil Martinson, MBBCh, MPH
James McIntyre, MBChB,MRCOG
Lerato Mohapi, MBBCH
Robin Wood, MD
India N. Kumarasamy, MBBS, PhD Tim Flanigan, MD Kenneth Mayer, MD OECS Kathleen Allen-Ferdinand, MD Paul Ricketts, MD Hazel Williams-Roberts, MD