Treatments, Current & Future Jon Cohen Science Magazine.
-
Upload
tabitha-darleen-wilkerson -
Category
Documents
-
view
215 -
download
0
Transcript of Treatments, Current & Future Jon Cohen Science Magazine.
Treatments, Current & Future
Jon Cohen
Science Magazine
Deciphering the Alphabet Soup:HIV Treatment Options and
Limitations
AZTd4TddIddCNVPEFVINDSQV3TCFTCT-20
RTNRTINNRTIPIFICD4CCR5VL
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
Know the Enemy
CD4 White Blood cell
HIV
CD4 Receptor
CCR5 Receptor
HIV’s Life Cycle: Dumbed down version
HIV CD4 White Blood Cell
HIV
HIVHIV
HIV
HIV
HIV
HIV
HIV’s Life Cycle: Smart version
HIV
CD4 cell
HIV’s Life Cycle Up close
1. Entry2. Reverse Transcription3. Integration4. Transcription5. Assembly6. Budding
U.S. FDAJune 2004
0
5
10
15
20
25
30
35
40
1995 1996 1997 1998 1999 2000 2001
Dea
ths p
er
10
0 P
ers
on
-Ye
ars
0
25
50
75
100
Pe
rce
nta
ge
of P
atie
nt D
ays o
n H
AA
RT
DEATHS
USE OF HAART
Mortality vs. HAART Utilization
Frank Palella/HOPS
The Cocktails Work
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
But a tangled web of serious problems—and important
stories—exist• Biological
Financial
• Political• Technical
• Practical
Resistance
Side Effects
The Story of Henan
Henan Province had 20% dropout first year, and NVP resistance in first 9 months was 20%-30%.
Solution: Direct Observation of Treatment Strategy (DOTS)
Solution: FDC(Fixed Dose Combination)
Solution: Proper training and monitoring
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
Future Treatment Possibilities
Structured Treatment Interruptions (STI): Little evidence that it works, but might
• Dybul et al, JID, 2004
Future Treatment Possibilities
New Targets
Future Treatment Possibilities
Immune Therapies
• Therapeutic vaccination
• Interleukin-2
• CD4 and CD8 cell infusions
Future Treatment PossibilitiesDrugs as Prophylaxis: Tenofovir Study
HIV treatment is jumping from river stone to river stone