1. Treatments, Current & Future Jon Cohen Science Magazine

2. Deciphering the Alphabet Soup: HIV Treatment Options and Limitations AZT d4T ddI ddC NVP EFV IND SQV 3TC FTC T-20 RT NRTI NNRTI PI FI CD4 CCR5 VL

3. Covering Key Treatment Issues Dizzying array of drugs Drugs target different vulnerable spots Problems w/drugs: Resistance, side effects Adherence: Simpler dosing badly needed Monitoring: too expensive for most Creative strategies: STIs, prophylaxis

4. Know the Enemy CD4 White Blood cell HIV CD4 Receptor CCR5 Receptor

5. HIV’s Life Cycle: Dumbed down version HIV CD4 White Blood Cell HIV

6. HIV’s Life Cycle: Smart version HIV CD4 cell

7. HIV’s Life Cycle Up close 1.Entry 2.Reverse Transcription 3.Integration 4.Transcription 5.Assembly 6.Budding

8. U.S. FDA June 2004

9. Percentage of Patient-days on HAART Deaths per 100 Person-Years Frank Palella/HOPS The Cocktails Work

10. WHO Recommended Cocktails in Resource-Limited Settings AZT/3TC* + NVP or EFV** 1 pill/2x day = 5 or 6 pills/day OR 1 pill/day *Alternatives to AZT/3TC: d4T/3TC, ZDV/ddI and ddI/3TC **Alternatives to NVP or EFV: PIs

11. But a tangled web of serious problems—and important stories—exist Biological Financial Political Technical Practical

12. Resistance

13. Side Effects

14. The Story of Henan Henan Province had 20% dropout first year, and NVP resistance in first 9 months was 20%-30%.

15. Solution: Direct Observation of Treatment Strategy (DOTS)

16. Solution: FDC (Fixed Dose Combination)

17. Solution: Proper training and monitoring

18. Lessons from Henan Biological: Resistance and side effects Financial: Lack of monitoring, training, and 2 nd line Tx Practical: Pills/day Technical: Do generics = brand name? Political: Export limits per WTO, No generic 3TC in China

19. Future Treatment Possibilities Structured Treatment Interruptions (STI): Little evidence that it works, but might Dybul et al, JID, 2004

20. Future Treatment Possibilities New Targets

21. Future Treatment Possibilities Immune Therapies Therapeutic vaccination Interleukin-2 CD4 and CD8 cell infusions

22. Future Treatment Possibilities Drugs as Prophylaxis: Tenofovir Study

23. HIV treatment is jumping from river stone to river stone