1. Routine HIV Screening in Portugal: Clinical Impact and Cost-Effectiveness Yazdan Yazdanpanah, MD Julian Perelman, PhD Joana Alves Kamal Mansinho, MD Madeline A. DiLorenzo Ji-Eun Park Elena Losina, PhD Rochelle P. Walensky, MD, MPH Farzad Noubary, PhD Henrique Barros, MD Kenneth A. Freedberg, MD, MSc A. David Paltiel, PhD, MBA

2. HIV Epidemiological Burden in Portugal 0 10 20 30 40 0.4% 0.3% 0.2% 0.1% 0% 2009 HIV Prevalence2009 Incidence Per Million Population Luxembourg Italy Ireland Belgium Switzerland Portugal Iceland Spain France Austria UK Netherlands Denmark Sweden Greece Germany Finland Norway

3. HIV Care in Portugal  The Portuguese National Health Service provides universal coverage for HIV care (including free access to HIV testing and ART) via a national network of public primary care centers and hospitals.  In 2011, the Portuguese Parliament adopted a resolution calling for voluntary, routine population-based HIV testing, counseling and referral (HIV-TCR).  Portugal faces numerous challenges in implementing this resolution.

4. 2010 GDP Challenge: Economic / Fiscal Crisis Source: Eurostat, ACSS <7,600€ 7,600-12,900€ 12,900-20,500€ >20,500€  2010 Portuguese GDP/capita: 16,300€  Mean 2010 EU GDP/capita: 24,000€  2011 GDP growth rate: -1.5%

5. Regional Disparities 2010 Annual HIV Incidence (%) < 0.005 0.005 - 0.009 0.010 - 0.020 > 0.020 2010 Undiagnosed HIV Prevalence (%) < 0.05 0.05 - 0.09 0.10 - 0.20 > 0.20

6. Objective  To evaluate the clinical impact and cost-effectiveness of routine HIV screening in Portuguese adults (vs. current practice), focusing on the regional heterogeneity in burden of disease.  We examined three different strategies:  One-time screening  Screening every 3 years  Annual screening

7.  Cost-Effectiveness of Preventing AIDS Complications (CEPAC), a widely published Monte Carlo simulation model of the detection, natural history and treatment of HIV disease.  Assembly of Portuguese national/regional input data on  Epidemiology of HIV infection  HIV clinical care  Economic resource use Methods Overview

8. VariableValueReference Undiagnosed HIV prevalence 0.16%Portuguese National Institute of Health 2010; Hammers & Philips, HIV Med, 2008 Annual incidence0.02%INSA 2010 Test offer/acceptance rate63.2%Assumption + Jauffret-Roustide, BEH, 2006 Linkage to care rate78.4%Portuguese CAD Report, 2010 Mean CD4 at care initiation 292 cells/μL2010 Survey at 3 Portuguese Hospitals HIV rapid test cost5.40€Ordinance 839-A/2009 Cost of 1 st Line ART (EFV + TDF/FTC) 732.05€Portuguese Central Administration of the Health System, 2010 Selected Input Parameters

9. VariableValueReference Undiagnosed HIV prevalence 0.16%Portuguese National Institute of Health 2010; Hammers & Philips, HIV Med, 2008 Annual incidence0.02%INSA 2010 Test offer/acceptance rate63.2%Assumption + Jauffret-Roustide, BEH, 2006 Linkage to care rate78.4%Portuguese CAD Report, 2010 Mean CD4 at care initiation 292 cells/μL2010 Survey at 3 Portuguese Hospitals HIV rapid test cost5.40€Ordinance 839-A/2009 Cost of 1 st Line ART (EFV + TDF/FTC) 732.05€Portuguese Central Administration of the Health System, 2010 Selected Input Parameters

10. Model Outcomes  Clinical (quality adjusted life years, or QALY)  Economic (per-person lifetime costs, 2010 €)  Incremental Cost-effectiveness (€/QALY)

11.  World Health Organization Commission on Macroeconomics and Health guidance:  “Cost-effective” if the CE ratio is less than three times the per capita GDP for a given country.  Portuguese GDP per capita is 16,300€, implying a threshold = 48,900 €/QALY.  Portuguese Infarmed “informal threshold” for cost- effectiveness of innovative drugs: ICER < 30,000 €/QALY. Source: Pordata, 2011 Benchmarks for Cost-Effectiveness in Portugal

12. Testing strategy Quality-adjusted life months HIV-infected 1 Quality-adjusted life months total population 1 Costs (€) 1,2 ICER (€/QALY) 3 Current practice 174.62193.21720 --- Screen once177.03193.2378036,000 Screen every three years 179.28193.2687053,000 Screen annually 181.07193.2798075,000 Base Case Results For National Program (Undiagnosed Prevalence = 0.16%, Annual Incidence = 0.02%) 1.Costs and quality-adjusted life months discounted at 5% per annum. 2.Costs rounded to nearest 10€. 3.ICERs are for the general population and are rounded to nearest 1000€/QALY. 1.Costs and quality-adjusted life months discounted at 5% per annum. 2.Costs rounded to nearest 10€. 3.ICERs are for the general population and are rounded to nearest 1000€/QALY.

13. Cost-Effectiveness of One-Time HIV Screening in Different Regions 2010 Annual Incidence (%) CE of National One- Time Screening Infarmed Threshold >WHO Threshold WHO CE Threshold 0.005-0.009 >0.020 0.010-0.020 <0.005 CE of Regional One- Time Screening

14. Cost-Effectiveness of HIV Screening Every Three Years in Different Regions 2010 Annual Incidence (%) CE of National Screening Every 3 Years Infarmed Threshold >WHO Threshold WHO CE Threshold 0.005-0.009 >0.020 0.010-0.020 <0.005 CE of Regional Screening Every Three Years

15. One-Way Sensitivity Analyses on CE of National, One-Time, Routine Screening HIV test cost (5.4€-42.7€) Mean CD4 at care initiation (255 cells/µL-350 cells/µL) Linkage to care rate (100%-15%) Test acceptance rate (100%-25%) Mean population age (37.6y-42.6y) Infarmed Threshold Base Case WHO Threshold Cost-effectiveness Ratio (€/QALY) First-line ART Costs (512€-732€)

16. Testing strategy Quality-adjusted life months HIV-infected 1 Quality-adjusted life months total population 1 Costs (€) 1,2 ICER (€/QALY) 3 Current practice 132.85185.746,720 --- Screen once138.96186.037,50033,000 Screen every three years 139.60186.057,620dominated* Screen annually 141.10186.127,88048,000 Risk Group Results - MSM (Undiagnosed Prevalence = 3.34%, Annual Incidence = 0.04%) 1.Costs and quality-adjusted life months discounted at 5% per annum. 2.Costs rounded to nearest 10€. 3.ICERs are for the general population and are rounded to nearest 1000€/QALY. 4.“dominated”: costs more and confers fewer QALYs than an alternative strategy. 1.Costs and quality-adjusted life months discounted at 5% per annum. 2.Costs rounded to nearest 10€. 3.ICERs are for the general population and are rounded to nearest 1000€/QALY. 4.“dominated”: costs more and confers fewer QALYs than an alternative strategy.

17. Testing strategy Quality-adjusted life months HIV-infected 1 Quality-adjusted life months total population 1 Costs (€) 1,2 ICER (€/QALY) 3 Current practice 109.88164.679,740 --- Screen once119.87165.6012,21032,000 Screen every three years 122.98165.8813,07036,000 Screen annually 126.58166.2114,08036,000 1.Costs and quality-adjusted life months discounted at 5% per annum. 2.Costs rounded to nearest 10€. 3.ICERs are for the general population and are rounded to nearest 1000€/QALY. 4.“dominated”: costs more and confers fewer QALYs than an alternative strategy. 1.Costs and quality-adjusted life months discounted at 5% per annum. 2.Costs rounded to nearest 10€. 3.ICERs are for the general population and are rounded to nearest 1000€/QALY. 4.“dominated”: costs more and confers fewer QALYs than an alternative strategy. Risk Group Results - IDU (Undiagnosed Prevalence = 6.69%, Annual Incidence = 0.09%)

18.  A simulation model of HIV screening and disease that combines input data from disparate sources and relies on multiple assumptions.  Impact of expended HIV screening on disease transmission was not considered.  “Cost-effective” ≠ “Affordable”. Budget impact analysis will be a useful next step to understand effects on individual stakeholders. Limitations

19. Summary and Conclusion  Overall, one-time screening of the national Portuguese population:  is “borderline cost-effective” by informal Portuguese national standards  is cost-effective by WHO standards.  Given the economic crisis as well as the higher disease burden in certain regions, we recommend initiating routine screening in high-prevalence regions first.  More frequent HIV screening may be considered in both high-risk populations (IDUs, MSM) and high-prevalence regions.

20. Escola Nacional de Saúde Pública – UNL Julian Perelman Joana Alves Céu Mateus João Pereira Instituto de Saúde Pública – U. do Porto Henrique Barros NHS hospitals - Portugal Kamal Mansinho, Ana Cláudia Miranda (CH Lisboa Ocidental) Francisco Antunes, Manuela Doroana (CH Lisboa Norte) Rui Marques (H São João) José Saraiva da Cunha, Joaquim Oliveira (HUC) José Poças (CH Setubal) Eugénio Teófilo (CH Lisboa Central) Acknowledgments Harvard Medical School Kenneth A. Freedberg Elena Losina Rochelle P. Walensky Farzad Noubary Madeline A. DiLorenzo Ji-Eun Park Yale School of Medicine A. David Paltiel Hôpital Bichat – U. Paris Diderot Yazdan Yazdanpanah Funding sources: Coordenação Nacional para a Infecção VIH/SIDA, Agence nationale de recherche sur le SIDA et les hépatites virales, National Institute of Allergy and Infectious Diseases, National Institute of Mental Health, National Institute on Drug Abuse.