1. Sustainable HIV Treatment in Africa through Viral Load-informed differentiated care: Evidence from modelling and economic analysis Operationalising 90:90:90 from inputs to outputs Rainbow Towers Conference Centre, Harare, Zimbabwe 2 December 2015 Andrew Phillips, Paul Revill, Tim Hallett & the Working Group on the Cost-Effectiveness of ART Monitoring Strategies

2. Budget constrained health care systems New interventions - Health gained - Additional Cost Interventions displaced or foregone - Health forgone - Resources released Goal: maximize health of the population Framework for informing policy decisions Is the health gain from the new intervention likely to be greater than the health foregone?

3. DALYs averted Incremental cost effectiveness ratio (ICER) 500,000250,000750,000 100 50 150 200 Increment in cost ($million) New interventions - Independent and mutually exclusive alternatives 5 1 1 1

4. DALYs averted Incremental cost effectiveness ratio (ICER) ICER = 50 m / 500,000 = $100 500,000250,000750,000 100 50 150 200 Increment in cost ($million) ICER = $100 means that with the introduction of the intervention you are paying $100 per DALY averted. 1 1 1 New interventions - Independent and mutually exclusive alternatives

5. DALYs averted Incremental cost effectiveness ratio (ICER) ICER = 50 m / 50,000 = $100 ICER = 150 m / 250,000 = $600 500,000250,000750,000 100 50 150 200 Increment in cost ($million) 1 1 1 New interventions - Independent and mutually exclusive alternatives

6. -How low does the cost of averting DALYs need to be for an intervention to be cost-effective ? Answering this question requires a “cost-effectiveness threshold” which reflects the value of resources (i.e. what else could they buy?) -For more poorly resourced health systems in sub-Saharan Africa, a cost-effectiveness threshold of $500 or lower is probably realistic, since many interventions offering health gains at this amount or less remain unfunded - Adoption of an intervention for which the ICER is above the threshold will mean that more health is lost/forgone from the commitment of resources to that intervention than results from its provision (i.e. we are not maximising population health with the budget available) Cost effectiveness threshold 8

7. No monitoring Clinical monitoring Clinical monitoring, VL confirmation Clinical monitoring, CD4 250 confirmation CD4 count monitoring 6m WHO CD4 count monitoring annual CD4 200 VL monitoring at 6m then annual 1000 threshold DBS Strategies initially evaluated

8. Cost of viral load $22 fully loaded cost. Cost of CD4 $10 fully loaded cost Cost of second line regimen including 20% supply chain costs $288 (Mylan). * Costs based on personal communication with Jen Cohn, MSF, and GFATM. Costs

9. VL monitoring enabling alternative models of ART delivery Knowledge that a person’s viral load is suppressed provides assurance of adherence and lack of resistance - and clinic and drug pick up visits can be reduced in frequency (eg clinic visits every 6mths, pharmacy pick up every 3 months) Non-ART programme costs (divided out as a cost per year per patient under care) assumed to be reduced from $80* to $40 per year if measured viral load < 1000 in past year * $80 per year informed by non-ART costs in the MATCH study (Zambia and Malawi) Tager et al PLoS ONE 2013;

10. ICER = $326 no monitoring DALYs averted Increment in cost ($1000) Clinical, monitoring Clinical monitoring CD4 confirmation Clinical monitoring viral load confirmation Viral load monitoring using DBS CD4 count monitoring (<200) CD4 count monitoring (WHO) Increment in costs and DALYs over 20 years (discounted) relative to no monitoring

11. VL test cost Saving in non-ART programme costs per year in people with viral suppression $12 $17 $22 $28 $35 $0 $10 $20 $30 $40 $50 $60 VLM Clinical What cost of viral load and saving in visit cost is required for viral load monitoring to be cost effective? cost effectiveness threshold $500

12. ICER = $326 no monitoring DALYs averted Increment in cost ($1000) Clinical, monitoring Clinical monitoring CD4 confirmation Clinical monitoring viral load confirmation Viral load monitoring using DBS CD4 count monitoring (<200) CD4 count monitoring (WHO) Increment in costs and DALYs over 20 years (discounted) relative to no monitoring

13. ICER = $326 no monitoring DALYs averted Increment in cost ($1000) Clinical, monitoring Clinical monitoring CD4 confirmation Clinical monitoring viral load confirmation Viral load- informed differentiated care using DBS CD4 count monitoring (<200) CD4 count monitoring (WHO) Increment in costs and DALYs over 20 years (discounted) relative to no monitoring Current situation: CD4 count monitoring (WHO) - low rate of switching

14. no monitoring DALYs averted Viral load - informed differentiad care using DBS – high rate of switching Current situation: CD4 count monitoring (WHO) - low rate of switching Increment in total cost over 20 years ($m) Cost effectiveness plane Current situation of CD4 count (WHO) monitoring with a low rate of switching in those meeting the failure criteria (0.05 per 3 months) - and viral load informed differentiated care with switch rate as in our base case (0.5 per 3 months)

15. If used to enable differentiated HIV care (whereby the frequency of clinic visits for patients stable on ART are reduced, with resulting cost savings), viral load monitoring is expected to be cost-effective even in the most resource- constrained settings. The costs of viral load testing and the savings in non-ART programme costs (as a result of differentiated care) are uncertain but crucial in determining whether routine viral load monitoring is cost-effective. Introduction of viral load-informed differentiated care accompanied by a high switch rate would lead to a substantial improvement in DALYs averted with a potential reduction in cost, compared with the current situation. Conclusions

16. Working Group on cost effectiveness of ART monitoring strategies – paper forthcoming in Nature Andrew Phillips, Ilesh Jani, Lisa Nelson, Rosanna Peeling, Fern Terris- Prestholt, Amir Shroufi, Kimberly Bonner, Valentina Cambiano, Lara Vojnov, Tom Ellman, David Dowdy, Brooke Nichols, Debbie Ford, Teri Roberts, Jennifer Cohn, Maurine Murtagh, Meghan Wareham, Kara Palamountain, Christine Chiedza Musanhu, Wendy Stevens, David Katzenstein, Andrea Ciaranello, Jens Lundgren, Ruanne Barnabas, Eran Bendavid, Kusum J Nathoo, David van de Vijver, David Wilson, Charles Holmes, Anna Bershteyn, Elliot Raizes, Fumiyo Nakagawa, Loveleen Bansi-Matharu, Alec Miners, Jeff Eaton, Rosalind Parkes-Rotanshi, Zachary Katz, David Maman, Nathan Ford, Marco Vitoria, Scott Braithwaite, Tim Hallett, Paul Revill. Funding: Bill and Melinda Gates Foundation

17. Thank you.