1. The epidemiological impact and cost-effectiveness of expanded eligibility for and access to adult antiretroviral therapy in South Africa, Zambia, India and Vietnam: a twelve model analysis JW Eaton, NA Menzies, J Stover, V Cambiano, L Chindelevitch, A Cori, JAC Hontelez, S Humair, CC Kerr, DJ Klein, S Mishra, KM Mitchell, BE Nichols, P Vickerman, T Bärnighausen, A Bershteyn, DE Bloom, M-C Boily, ST Chang, T Cohen, PJ Dodd, C Fraser, C Gopalappa, J Lundgren, NK Martin, E Mountain, QD Pham, M Pickles, A Phillips, L Platt, C Pretorius, HJ Prudden, JA Salomon, DAMC van de Vijver, BG Wagner, RG White, DP Wilson, L Zhang, J Blandford, G Meyer-Rath, M Remme, F Terris-Prestholt, P Revill, N Sangrujee, M Doherty, P Easterbrook, G Hirnschall, TB Hallett 7 th IAS Conference on HIV Pathogenesis, Treatment and Prevention Kuala Lumpur Malaysia, 1 July 2013 Acknowledgements: Ellen McRobie Funding:

2. Questions for programmes ART eligibility: – Given an HIV+ person in care, should they be initiated on ART if they have a CD4 > 350 cells/µL? Program scale-up priorities: – Should programmes devote resources to (i) expanding access following current ART guidelines, or (ii) immediately adopt new ART eligibility guidelines? Strategic prioritisation: – Are there certain populations that should be prioritised for expanded access and earlier ART?

3. Model analyses Eligibility x access strategies projected over 20 years (2014–2033) US$/DALY averted compared to current access & eligibility ART eligibility CD4 ≤350 (current) CD4 ≤500, all HIV+ Pregnant women, serodiscrodant couples, >50 years MSM, FSW, PWID ART access Status quo Uniformly expanded access Prioritized expanded access Health benefits Infections averted Adult mortality DALYs averted Costs ART Pre-ART HIV testing & linkage Other healthcare Settings: South Africa (7 models) Zambia (4 models) India (3 models) Vietnam (1 model)

4. Mathematical models ModelSettingTypeAge- struct General pop Key populationsDrop- out ART GoalsSA/Zambiadeterm. ✓✓ couples, preg., CSW, MSM, PWID ✗ STDSIMSAstoch. ✓✓ couples, preg., CSW, age > 50 ✓ EMODSA/Zambiastoch. ✓✓ couples, preg, age>50 ✓ BBHSAdeterm. ✗✓ CSW, MSM ✗ PopARTSA/Zambiadeterm. ✗✓✓ SynthesisSAstoch. ✓✓✓ MenziesSAdeterm. ✗✓✗ MachaZambiadeterm. ✗✓✓ PruddellBangaloredeterm. ✗✗ CSW, MSM ✓ MishraBelgaumdeterm. ✗✓ CSW ✓ IDU Manipur Manipurdeterm. ✗✗ PWID, HCV ✓ PrevtoolVietnamdeterm. ✗✓ CSW, MSM, PWID ✓

5. Impact on HIV incidence South Africa Zambia

6. Impact on HIV incidence India – sexual tranmsission India – injectingVietnam

7. 7 1. Cost Areas2. Services 3. Resource Use 4. Unit Costs 5. Total Costs ART ARVs (annual) ART initiation Non-ARV (annual) Estimates by models Reg dist x price Volume X Unit Cost, summed over services and years Bayesian evidence synthesis Pre-ART Pre-ART (annual) Diagnosis and linkage to care HTC Reaching high risk groups Utilization in routine health system TB treatment Advanced HIV care Terminal illness WHO- CHOICE Higher-level program support Supply-chain mgmt General support % mark-up on other costs Expert opinion Mark-up Costing approach

8. 8 Unit costs: predictions vs. data

9. Cost-effectiveness of earlier eligibility Cost per DALY averted over 20 years (3% discount per annum):

10. Costs of program expansion Incremental cost of expanded eligibility and access (South Africa; 20 years, undiscounted): Eligibility for All vs. Status Quo Expanded Access vs. Status Quo

11. Earlier eligibility or expanded access? Uniform expansion of testing and immediate treatment for all Treat all HIV-infected persons that in care/will enter care Current eligibility criteria and testing levels. Uniform expansion of testing and treat <500 Uniform expansion of testing with no change in eligibility Treated persons with CD4<500 that are in care/will enter care. $237/ DALY averted $795/ DALY averted

12. Earlier eligibility or expanded access?

13. Prioritised access in concentrated epidemics Vietnam: (GDP $1407 pppy) $2043 / DALY $24,610 / DALY $290 / DALY

14. Conclusions http://www.hivmodelling.org Expanded ART eligibility appears ‘cost-effective’ (CD4 ≤500 or all HIV+). Cost of initiating ART vs. waiting are small, given a patient in care. Expanded testing and linkage appears ‘cost-effective’ in generalised epidemic settings. In concentrated epidemic settings, immediate eligibility and expanded access to high-risk populations appears highly cost-effective. Consensus conclusions across many models increases confidence in policy recommendations based on modelling. Conclusions must be reevaluated when new data are available (esp. when-to-start trials, community combination prevention trials). Other considerations for programmes, e.g. equity.