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Treatments, Current & Future

Treatments, Current & Future. Jon Cohen Science Magazine. Deciphering the A l p h a b e t 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. Covering Key Treatment Issues. Dizzying array of drugs

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Treatments, Current & Future

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  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 HIV CCR5 Receptor CD4 Receptor CD4 White Blood cell

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

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

  7. HIV’s Life Cycle Up close • Entry • Reverse Transcription • Integration • Transcription • Assembly • Budding

  8. U.S. FDA June 2004

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

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

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

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

  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

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