1. Why we shouldn’t (yet) move to TDF/FTC as the primary first line regimen for PEPFAR-supported programs Barbara Marston, M.D. Care and Treatment Team, GAP, Atlanta

2. Considerations in choice of first line regimen TDFd4T Effectiveness Side Effects Impact on Resistance Drug interactions Impact on co-infections Impact on adherence (# of pills, # of doses, tolerability) Supply chain (FDCs, shelf life, storage conditions) Costs

3. Effectiveness of TDF Potent, well-tolerated, once daily drug In once daily regimens, ~superior to d4t in twice a day regimens and superior to ZDV given in twice a day regimens Not clear how this might translate in Africa –Concern with routine EFV in women of child bearing age –Not certain that effectiveness will hold up with NVP Discomfort with NVP in once daily regimen Giving NVP twice daily might balance some of the TDF advantage –FDCs with NVP not yet available –Effectiveness of TDF in these studies might have been in part related to daily dosing

4. Advantages of FDCs Contribute to adherence Reduce risk of taking partial regimens, stock outs Contribute to simplicity with respect to forecasting/procurem ent/distribution

5. Costs Consider costs in general, not just for PEPFAR Consider not just the cost of this action but the costs in the context of other things we’re not doing Many ways to consider costs Can we reduce costs?

6. Costs Important to consider costs in general, not just for PEPFAR –An isolated decision to use TDF in PEPFAR programs would be “problematic” –Important that choice of first line regimens not be a PEPFAR decision, but a series of national decisions

7. Costs Need to consider not just the cost of this action (“should we do it”) but the costs in the context of other things we’re not doing (“should we do this, or should we spend additional money on prevention, cotrimoxazole, immunizations, education”). Shameless plug for CTX (cost savings of $2.50 to cost of $6 per DALY vs. ~$600 per DALY for ART)

8. Costs There is potential to further reduce costs, but TDF costs are likely to remain higher than stavudine costs –5x the raw materials –6-7 step production vs. 1 step Can consider costs in many ways (costs of TDF only, costs of regimens with or without TDF, costs of health care with or without TDF). The question is not whether TDF is superior to d4T for 1 person—the question is “What is the best thing to do with the money?” –Drugs only (adding ARVs for an additional person) 2:1 –Add people on treatment 5:4

9. Or

12. 5:4 may look like a modest difference, but…

13. Measuring Progress in Treatment 07 SAPR Data Total in need of ART Total currently receiving ART Percentage of coverage 550,0001000,000 Mozambique

14. There is an enormous unmet need Terrific progress toward targets, but… We are no where near universal access –~7M currently in immediate need of ART –~2M currently accessing treatment (probably includes some people not in the denominator) –Even if we stopped HIV in its tracks, need will grow astronomically (see Jeff’s slide) –We haven’t stopped HIV in its tracks

15. Barb’s thoughts No need for this to be an “all-or-none decision” Reasonable to consider TDF regimens for those with hepatitis or SEs from stavudine I would shy away from use of “PEPFAR- Supported” as the criterion for determining drug choice Need to evaluate durability of viral suppression with TDF in Africa, develop NVP- based FDCs Think hard about priorities and the people you can’t see Maybe we just need more money.

16. Thank You

17. ARVs OI drugs Personnel, infrastructure Non- ARV Costs of providing HIV care to a population

18. ARVs OI drugs Personnel, infrastructure Non- ARV Add an expensive ARV

19. ARVs OI drugs Personnel, infrastructure Non- ARV Add a less expensive ARV

20. ARVs OI drugs Personnel, infrastructure Non- ARV Add people without ARVs

21. ARVs OI drugs Personnel, infrastructure Non- ARV Add people with less expensive ARVs

22. ARVs OI drugs Personnel, infrastructure Non- ARV Add people with more expensive ARVs