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

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

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, 1994. NEJM 1998;339:861-7. LE LE gains from angioplasty: Kuntz et al, Cost-effectiveness of routine coronary angiography after acute MI. Circulation. 1996;94:957-965. 1)      LE gains from beta-blockers: Phillips K et al Health and economic benefits of increased b-blocker use following an MI. JAMA 2000;284:2748-2745. 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. 2005;45:838-45). Walensky et al. JID, 2006

November 2009

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

“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 11.71 years with deferred ART, and 12.48 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

When is Antiretroviral Therapy Started? Late! Review of data from 2003-2005 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.

When is Antiretroviral Therapy Started? Review of data from 2003-2005 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.

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 11.71 years with deferred ART, and 12.48 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: http://who.int/hiv/pub/towards_universal_access_report_2008.pdf

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

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

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

High Rate of Mortality 15% of HIV-infected cohort

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

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

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

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

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)

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

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: http://who.int/hiv/pub/towards_universal_access_report_2008.pdf 20

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

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 2012. In the moderate growth scenarios, shown in orange, treatment coverage increases steadily to reach 97% of those in need by 2012. The rapid growth scenario, shown in purple, achieves full treatment coverage by 2011. Year Walensky et al. JID 2008 23

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

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.

“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 11.71 years with deferred ART, and 12.48 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

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