1. HIV Testing and Treatment: The Magnitude of the Impact
Rochelle P. Walensky, MD, MPH
Associate Professor of Medicine
Harvard Medical School
Division of Infectious Diseases
Massachusetts General Hospital
Brigham and Women’s Hospital
Supported by NIAID, NIMH, and CDC

2. Overview Treatment successes in HIV/AIDS
New WHO HIV treatment guidelines
When to initiate antiretroviral therapy
HIV screening
Impact of alternative PEPfAR scale-up strategies
PEPfAR in the context of maternal/child health

3. HIV Treatment is Very Effective: Survival Gains for Disease Interventions
This slide shows the per person survival gains with various disease interventions in the US. The vertical axis is now in months.
Survival gains for non-small-cell lung cancer related chemotherapy, adjuvant chemotherapy for breast cancer, treatment during and after an acute myocardial infarction, and bone marrow transplantation for relapsed non-Hodgkins lymphoma are shown in yellow. When not available directly from the literature, these LE estimates were synthesized from a compilation of numerous sources. In comparison, in orange, we see interventions in AIDS care. While OI prophylaxis led to a modest 3-month benefit, antiretroviral therapy has resulted in 160 months of survival gain. That is, it has increased the per person life expectancy of patients with AIDS by 13 years.
Sources:
Survival from thrombolytics during an MI: (Wright and Weinstein NEJM 1998 cite a 1992 paper from European Heart Journal
1)  P(MI survival): Rosamond W et al Trends in the Incidence of MI and in Mortality due to coronary Heart Disease, 1987, NEJM 1998;339:861-7.
LE LE gains from angioplasty: Kuntz et al, Cost-effectiveness of routine coronary angiography after acute MI. Circulation. 1996;94:
1)      LE gains from beta-blockers: Phillips K et al Health and economic benefits of increased b-blocker use following an MI. JAMA 2000;284:
LE gains from clopidogrel: Weintraub et al. Long-term cost-effectivenss of clopidogrel given for up to one year in patients with acute coronary syndromes without ST elevation. Journal of the America College of Cardiology ;45:838-45).
Walensky et al. JID, 2006

4. November 2009

5. The proposed changes Replacement of stavudine with tenofovir
Increased number of sequential ART regimens
Earlier ART initiation at CD4 <350/µl instead of <200/µl

6. “When to Start” Strategies Impact over the next 5 years (South Africa)
Strategy
Total OIs
Total Deaths
ART at CD4 <350/μl
730,272
244,249
ART at CD4 <250/μl
951,370
497,059
Difference (<350 - <250/μl)
(221,097)
(252,810)
When long term outcomes are projected, the two ART strategies result in mean life expectancy of years with deferred ART, and years with earlier ART. Per person lifetime costs of deferred ART are $12,730, compared to $13,620 with earlier ART. The incremental cost effectiveness of deferred ART compared to no treatment is $1,100/life year saved and of earlier ART compared to deferred ART is $1200/life years saved.
OI: opportunistic infection
( ): denotes fewer ODs and deaths with ART at <350/μl
Walensky et al. Ann Int Med, 2009

7. When is Antiretroviral Therapy Started?
Late!
Review of data from from 42 countries, 176 sites, n=33,008
Since 2000, CD4 at initiation in developed countries stable at about 175 cells/µl, increasing in Sub-Saharan Africa from 50  100 cells/µl.
Egger M, 14th CROI, Los Angeles 2007, #62.

8. When is Antiretroviral Therapy Started?
Review of data from from 42 countries, 176 sites, n=33,008
Since 2000, CD4 at initiation in developed countries stable at about 175 cells/µl, increasing in Sub-Saharan Africa from 50  100 cells/µl.
Egger M, 14th CROI, Los Angeles 2007, #62.

9. Percent HIV-infected adults who were tested and received result
Country
Overall
Dominican Republic
60.7
Swaziland
38.7
Rwanda
31.4
Haiti
24.5
Zimbabwe
23.7
Côte d’Ivoire
16.5
India
10.8
Democratic Republic of Congo
10.5
Ethiopia
7.6
When long term outcomes are projected, the two ART strategies result in mean life expectancy of years with deferred ART, and years with earlier ART. Per person lifetime costs of deferred ART are $12,730, compared to $13,620 with earlier ART. The incremental cost effectiveness of deferred ART compared to no treatment is $1,100/life year saved and of earlier ART compared to deferred ART is $1200/life years saved.
WHO:

10. HIV Screening 2 Outpatient Depts: Durban, South Africa 2008
HIV Testing
2,775
No test/result: 71
Indeterminate: 6
HIV-negative
1,308
HIV-infected
1,467
54% HIV prevalence
Bassett et al. AIDS 2010

11. Median time to ART initiation: 100 days
How many start ART?
HIV Tested
HIV-infected
CD4/results
Eligible for ART
Start ART
2,775
1,467
605
Failure to
obtain CD4
368
154 (42%)
Failure to
start ART
when eligible
Median time to ART initiation: 100 days
Bassett et al. AIDS 2010

12. High Rate of Mortality 15% of HIV-infected cohort
Bassett et al. AIDS 2010

13. High Rate of Mortality 15% of HIV-infected cohort

14. ART Roll Out in South Africa: The impact of speed on survival
To examine alternative ART rollout scenarios in South Africa and to forecast number of lives lost while awaiting therapy
Our objectives were to examine alternative ART rollout scenarios in South Africa to:
First, forecast the number of lives lost while awaiting therapy among treatment-eligible patients, and the number of patients in treatment over the next several years;
Second, to project when total ART need would be met;
And third, to inform decisions regarding the life-saving value of alternative treatment expansion scenarios.
Walensky et al JID 2008 14

15. 4 Growth Scenarios Zero growth 100,000 Constant growth 600,000
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
We examine four different growth scenarios for ART rollout. These scenarios are similar to proposals made by the Actuarial Society of South Africa, or ASSA, and the South African Joint Task Team on HIV/AIDS. They range from a zero-growth scenario, which provides 750,000 new treatment slots by 2010, to a rapid growth scenario, which provides 2.8 million treatment slots by 2010.
Walensky et al JID 2008 15

16. Projected Deaths & Alive on ART: South Africa, 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
This table shows the number of AIDS deaths and patients alive on ART for 2005 to 2010, as we total the deaths for each year from the previous slide. The number of AIDS deaths ranges from 2,197,000 in the zero growth scenario, down to 1,161,000 in the rapid growth scenario. The number of patients alive and receiving therapy ranges from 693,000 in the zero growth scenario to 2,572,000 in the rapid growth scenario.
Walensky et al JID 2008 16

17. 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
This table shows the number of AIDS deaths and patients alive on ART for 2005 to 2010, as we total the deaths for each year from the previous slide. The number of AIDS deaths ranges from 2,197,000 in the zero growth scenario, down to 1,161,000 in the rapid growth scenario. The number of patients alive and receiving therapy ranges from 693,000 in the zero growth scenario to 2,572,000 in the rapid growth scenario.
Walensky et al JID 2008 17

18. Are HIV Testing &Treatment Cost-Effective in These Settings?
Routine HIV screening (South Africa)
YES: $1,940/YLS for annual screening compared to screening every 5 years (Walensky, CROI 2009)
ART in resource-limited settings (Côte d’Ivoire)
YES: $590/YLS compared to no ART (Goldie, NEJM 2006)
ART initiation at CD4 <350/µl (South Africa)
YES: $1,200/YLS ART at ≤350 cells/µl vs ART at CD4 ≤250 cells/µl (Walensky Ann Intern Med 2009)

19. PEPfAR & Maternal/Child Health
HIV testing, access to care, treatment and maternal/child health are linked at the core
Allows for prevention of mother to child HIV transmission
Allows for safe breastfeeding in lieu of formula feeding with potentially contaminated water
Prevents orphan-associated mortality
10X increase risk of death
Our objectives were to examine alternative ART rollout scenarios in South Africa to:
First, forecast the number of lives lost while awaiting therapy among treatment-eligible patients, and the number of patients in treatment over the next several years;
Second, to project when total ART need would be met;
And third, to inform decisions regarding the life-saving value of alternative treatment expansion scenarios. 19

20. PEPfAR & Maternal/Child Health
Our objectives were to examine alternative ART rollout scenarios in South Africa to:
First, forecast the number of lives lost while awaiting therapy among treatment-eligible patients, and the number of patients in treatment over the next several years;
Second, to project when total ART need would be met;
And third, to inform decisions regarding the life-saving value of alternative treatment expansion scenarios.
WHO: 20

21. Conclusions
Life saving benefits of ART in HIV disease are greater than for virtually any other adult disease
Globally, these benefits can be increased by:
Increasing HIV testing and diagnosis
Increasing access to earlier ART
Making better drugs available
HIV testing and treatment are very cost-effective
HIV testing and treatment form the foundation for maternal/child health in areas of high HIV prevalence

23. Results: Percent ART Need Met by Year
Rapid
Moderate
Constant
% ART Need Met
Zero
This results slide shows the percent ART need met by year. On the horizontal axis is the year, and on the vertical axis, the percent of ART need met. All scenarios begin with the same number of patients treated in 2007, and hence the same percent of coverage; they then diverge in subsequent years. Treatment coverage under the zero growth scenario, shown in white, decreases steadily through 2012 at which time 28% of people in need of therapy will receive it. In the constant growth scenario, shown in yellow, treatment rates stay relatively unchanged to achieve 52% of necessary coverage by In the moderate growth scenarios, shown in orange, treatment coverage increases steadily to reach 97% of those in need by The rapid growth scenario, shown in purple, achieves full treatment coverage by 2011.
Year
Walensky et al. JID 2008 23

24. Proportion Alive at 5 Years
Earlier ART
Deferred ART
No treatment
Model-generated survival curves also diverge for the three ART strategies. No treatment, in blue, has 50% survival at 4.2 years. By year 3, earlier ART maintains a consistent 6% absolute increase in the proportion alive.
Walensky et al. Ann Int Med 2009 24

25. AIDS Survival by Era
This figure shows model-based survival curves for patients diagnosed in the first year of each of the six treatment eras (1989, 1993, 1996, 1998, 2000, 2003) and untreated disease, shown in gray. The area between the curves illustrates the improvement in AIDS-associated survival in the US over time. Median survival was 1.7 years for the PCP era shown in yellow, 7.5 years for ART 1 shown in light blue, and 14.1 years for ART 4, the upper most curve shown in pink.

26. “When to Start” Strategies Impact over the next 5 years (South Africa)
Strategy
Total OIs
Total Deaths
Discounted Total Costs ($)
ART at CD4 <350/μl or OI
730,272
244,249
12,054,287,800
ART at CD4 <250/μl or OI
951,370
497,059
10,634,516,900
Difference (<350 - <250/μl)
(221,097)
(252,810)
1,419,770,900
When long term outcomes are projected, the two ART strategies result in mean life expectancy of years with deferred ART, and years with earlier ART. Per person lifetime costs of deferred ART are $12,730, compared to $13,620 with earlier ART. The incremental cost effectiveness of deferred ART compared to no treatment is $1,100/life year saved and of earlier ART compared to deferred ART is $1200/life years saved.
OI: opportunistic infection
( ): denotes fewer ODs and deaths with ART at <350/μl

27. CD4 count within 90 days HIV-infected 1,467 Yes 607 No 862
59% no CD4
within 90 days
CD4<200/μl
368
CD4≥200/μl
237
61% CD4<200/µl
ART eligible
at baseline
Bassett et al. AIDS 2010