Y.Yazdanpanah ( yazdan.yazdanpanah@bch.aphp.fr )

1. Les études de coût-efficacité influencent-elles les recommandations? Y.Yazdanpanah (yazdan.yazdanpanah@bch.aphp.fr) Service des Maladies Infectieuses et Tropicales Hôpital Bichat Claude Bernard Equipe ATIP/Avenir INSERM (U1137) : "Modélisation, Aide à la Décision, et Coût-Efficacité en Maladies Infectieuses"   Université Paris Diderot: site Bichat

3. Revised Recommendations for HIV Testing of Adults, Adolescents, and Pregnant Women in Health-Care Settings • « HIV screening is recommended for patients in all health-care settings after the patient is notified that testing will be performed unless the patient declines » • « Prevention counseling should not be required with HIV diagnostic testing or as part of HIV screening programs in health-care settings. » MMWR September 22, 2006 / 55(RR14);1-17

4. Si pas de test de résistance : 25% des patients = Trt comportant Lopi/r 75% des patients = Trt comportant Efavirenz

5. Prise en charge médicale des personnes infectées par le VIH; Rapport 2006 • Il est recommandé de faire un test génotypique de résistance avant l'initiation d'un traitement antirétroviral : • La fréquence d’infection par des virus résistants. • L’impact délétère de la présence de mutations de résistance sur la réponse virologique • L’importance du premier traitement sur l’évolution de la maladie. • Le coût et l’efficacité.

6. CV < 50 copies/ml à 24 semaines = 78% vs 85% • Echappement après 24 semaines = 5.4 vs. 2.5 • Coût/année = US$ 9200 vs. 15300 • Ratio Coût-efficacité = • US $ 114 800/QALY gagné • (CE ratios > 3 x PIB/habitant) “Estimated first-year savings, if all eligible U.S. patients start or switch to generic-based ART, are $920 million”

7. “The study should serve as a wake-up call to clinicians who care for people with HIV: The era of generic antiretrovirals in the United States has come.” Would even a small reduction in the efficacy be acceptable? Sherer et al. 2013

8. En tenant compte du coût des différentes associations disponibles.

9. Supported by the ANRS, NIAID, Doris Duke Charitable Foundation Cost-effectiveness of cART = $ 1180/YLS < 3 x Côte d’Ivoire GDP/capita (708 $) = “cost-effective” Goldie et al. N Engl J Med 2006

10. d4T vs Tenofovir (cost issue) Using tenofovir as part of first-line ART in India will improve survival, is cost-effective by international standards Clin Infect Dis 2010 AIDS 2011

11. Strategies to monitor ART efficacy Lancet 2008 J AIDS 2010 Archives Intern Med 2008 Lancet Infect Dis 2013

12. Interpretation—Earlier ART eligibility is estimated to be very cost-effective in low- and middle-income settings.

14. 2013

15. Methods and process for developing the guidelines The following sources of information were used in developing new recommendations • Mathematical modelling on the impact and cost–effectiveness of earlier ART in various populations and settings

16. Methods and process for developing the guidelines The following sources of information were used in developing new recommendations • Mathematical modelling on the impact and cost–effectiveness of earlier ART in various populations and settings • An impact assessment • Reports on country implementation experiences • Consultations with health workers • Two global community and civil society consultations • Systematic reviews

17. The proposed recommendations were then considered encompassing the following elements • Benefits and risks; • Community and health care worker values and preferences; • Costs and resource implications; cost-effectiveness; • Feasibility and barriers to implementation; equity, • Ethics and human rights implications;

19. Interpretation—Earlier ART eligibility is estimated to be very cost-effective in low- and middle-income settings, although these questions should be revisited as further information becomes available. Scaling-up ART should be considered among other high-priority health interventions competing for health budgets.

20. Effectiveness, cost, and cost-effectiveness of new interventions: Strategies that should be considered not one by one but in light of each other • PreP • TasP • Testing

21. Objective • Generalised Epidemics in Southern Africa (n =7) • Concentrated Epidemics among MSM in the USA (n =4) • Concentrated Epidemics among MSM in Peru (n =1) • Concentrated Epidemics among People Who Inject Drugs in Ukraine (n =1)

22. Objective • It is worth noting that, with the exception of four studies in • South Africa [28,30,36,37], research comparing the potential trade-offs of earlier treatment for prevention versus PrEPremains an important gap in the literature that should be addressed, • especially in concentrated epidemics

23. AIDS 2013 Coverage 80% Coverage 40% of 15-24 years Effectiveness 70%

24. AIDS 2013 Cost per infection averted = $39 900 Cost per infection averted = $10 530 ART delivery cost 600 US$/y PreP delivery cost 252 US$/y

25. The financial consequences of introducing a new technology in a specific setting over the short to medium term : affordability

26. AIDS 2013 ART delivery cost 600 US$/y PreP delivery cost 252 US$/y

27. Hépatite C • From 2% to 3% of the world population with a chronic HCV1 • 350,000 deaths from liver complications per year2 • The most concerned regions are East and Central Asia, North Africa and Middle East3 1 Lavanchy D et al, Clin Microbiol Infect 2011 2 WHO, HCV factsheet, 2014 3 Mohd Hanafiah et al, Hepatology 2013

28. Clin Infect Dis 2012 • Key priorities for scaling up HCV treatment and care include: • reducing the cost of current and future treatment; • simplifying the package of care; • identifying opportunities to shift specific tasks to nonspecialists to overcome human resource constraints;

29. Slide, adaptedfrom Pr Gamal Esmat

30. Egypt : highest HCV prevalence in the world (15% vs. <1% in France) • About 4 000 000 HCV-infected patients • How should we prioritize?

32. Treatment efficacy Treatmentefficacywith dual therapy For F0-F1-F2 patients  SVR=64.9% For F3-F4 patients  SVR=39.6% Analyse de sensibilité : Sofosbuvir Gad et al, Liver International, 2008

33. Effectiveness and cost-effectiveness of immediate vs. delayed treatment of HCV-infected patients in a country with limited resources: the case of Egypt (ANRS 12215) Obach et al. Clin Infect Dis, 2014 • Cost-effectivenessanalysis • If we do not have enoughdrugsitisbetter to treat F4 patients than F0 or F1 patients (in term of life-yearssaved) Treating F4 patients is cost-effective (ICER<3*GDP = 8500$)

34. General conclusion • Impact on Egyptian national treatment guidelines in 2013 • Treatment to patients at stages ≥ F2 • Reference for the treatment recommendations in limited settings of WHO 2014 guidelines

35. How to optimize HCV treatment impact on life years saved in countries with resources constraints * Experts’ opinion 1 El-Zanaty et al, Egypt Demographic and Health Survey 2008 2Mohamed et al, J Med Virol 2006 3Lavanchy, Clin Microbiol Infect 2011 4World Health Organization 5 Sievert et al, Liver Int 2011 6 Combe et al, Trans R Soc Trop Med Hyg 2001 7 Hépatites en Afrique, 2013 8 News Abidjan, 2013 9 Kouassi-M Bengue et al, Scientific Research and Essay 2008

36. ResultsBaseline analysis (pegylated IFN+RBV)

37. ResultsBaseline analysis (pegylated IFN+RBV)

38. Conclusions • What economic evaluation is: • a means for evaluating the economic impact of clinical decisions • quantitative analysis for qualitative insight • What Economic Evaluation is Not: “The answer” 38

39. Economic evaluation One component useful for clinical policy development alongside with other issues including fairness, ethics, and political concerns 39

40. Inserm, Avenir team « Decision Sciences in Infectious Disease Prevention, Control and Care » 40