Treatments, Current & Future Jon Cohen Science Magazine.

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Treatments, Current & Future Jon Cohen Science Magazine

Transcript of Treatments, Current & Future Jon Cohen Science Magazine.

Page 1: Treatments, Current & Future Jon Cohen Science Magazine.

Treatments, Current & Future

Jon Cohen

Science Magazine

Page 2: Treatments, Current & Future Jon Cohen Science Magazine.

Deciphering the Alphabet Soup:HIV Treatment Options and

Limitations

AZTd4TddIddCNVPEFVINDSQV3TCFTCT-20

RTNRTINNRTIPIFICD4CCR5VL

Page 3: Treatments, Current & Future Jon Cohen Science Magazine.

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

Page 4: Treatments, Current & Future Jon Cohen Science Magazine.

Know the Enemy

CD4 White Blood cell

HIV

CD4 Receptor

CCR5 Receptor

Page 5: Treatments, Current & Future Jon Cohen Science Magazine.

HIV’s Life Cycle: Dumbed down version

HIV CD4 White Blood Cell

HIV

HIVHIV

HIV

HIV

HIV

HIV

Page 6: Treatments, Current & Future Jon Cohen Science Magazine.

HIV’s Life Cycle: Smart version

HIV

CD4 cell

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HIV’s Life Cycle Up close

1. Entry2. Reverse Transcription3. Integration4. Transcription5. Assembly6. Budding

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U.S. FDAJune 2004

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USE OF HAART

Mortality vs. HAART Utilization

Frank Palella/HOPS

The Cocktails Work

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WHO Recommended Cocktails in Resource-Limited Settings

AZT/3TC*

+ NVP or EFV**

1 pill/2x day1 pill/2x day1 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

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But a tangled web of serious problems—and important

stories—exist• Biological

Financial

• Political• Technical

• Practical

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Resistance

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Side Effects

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The Story of Henan

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

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Solution: Direct Observation of Treatment Strategy (DOTS)

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Solution: FDC(Fixed Dose Combination)

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Solution: Proper training and monitoring

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Lessons from Henan

• 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

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Future Treatment Possibilities

Structured Treatment Interruptions (STI): Little evidence that it works, but might

• Dybul et al, JID, 2004

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Future Treatment Possibilities

New Targets

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Future Treatment Possibilities

Immune Therapies

• Therapeutic vaccination

• Interleukin-2

• CD4 and CD8 cell infusions

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Future Treatment PossibilitiesDrugs as Prophylaxis: Tenofovir Study

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HIV treatment is jumping from river stone to river stone