Treatments, Current & Future

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

CCR5 Receptor

CD4 Receptor

CD4 White Blood cell

 HIV’s Life Cycle: Dumbed down
version

HIV
HIV

HIV
HIV CD4 White Blood Cell HIV
HIV

HIV

HIV
HIV’s Life Cycle: Smart version

HIV

CD4 cell
 HIV’s Life Cycle Up close

1. Entry
2. Reverse Transcription
3. Integration
4. Transcription
5. Assembly
6. Budding
U.S. FDA
June 2004
 The Cocktails Work
Mortality vs. HAART Utilization
40 100

P ercentage of P atient D ays on H AAR T

35
D eaths p er 100 P erson -Y ears

30 USE OF HAART 75

25
DEATHS
20 50

15

10 25

0 0
1995 1996 1997 1998 1999 2000 2001

Frank Palella/HOPS
WHO Recommended Cocktails
in Resource-Limited Settings

AZT/3TC*
**Alternatives
*Alternatives + NVP or EFV** to NVP or EFV:
to AZT/3TC: PIs
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
 But a tangled web of serious
problems—and important
stories—exist
• Biological
Financial
• Practical

• Technical • Political
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 • Technical: Do
generics = brand
name?
• Financial: Lack of
monitoring, training,
and 2nd line Tx • Political: Export
limits per WTO, No
• Practical: Pills/day 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 Possibilities
Drugs as Prophylaxis: Tenofovir Study
HIV treatment is jumping from river
stone to river stone