aids treatments, current and future (jon cohen)

8/7/2019 AIDS Treatments, current and future (Jon Cohen)

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Treatments, Current & Future

Jon Cohen

Science Magazine



Deciphering the Alphabet Soup:

HIV Treatment Options andLimitations

AZT

d4TddI

ddC

NVP

EFV

IND

SQV3TC

FTC

T-20

RTNRTI

NNRTI

PI

FI

CD4

CCR5VL



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

HIV

HIV

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



Percentag

Deaths per 100 Person-Years

0

5

10

15

20

25

30

35

40

1995 1996 1997 1998 1999 2000 2001

Deaths per 100 Person-Y

0

25

50

75

100

P er cent age

of P at i ent Days

on HAART

DEATHS

USE OF HAART

Mortality vs. HA ART Utilizatio n

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

**Alternativesto NVP or EFV:

PIs



But a tangled web of serious

problems²and importantstories²exist

� 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

(FixedD

ose Combination)



Solution: Proper training and

monitoring



Lessons from

Henan

� Biological:Resistance and sideeffects

� Financial: Lack of monitoring, training,and 2nd line Tx

� Practical: Pills/day

� Technical: Dogenerics = brandname?

� Political: Exportlimits per WTO, Nogeneric 3TC inChina



Future Treatment Possibilities

Structured Treatment Interruptions (STI):

Little evidence that it works, but might

� Dybul et al, JID, 2004




New Targets




Immune Therapies

� Therapeutic vaccination

� Interleukin-2

� CD4 and CD8 cell infusions




Drugs as Prophylaxis: Tenofovir Study



HIV treatment is jumping from river

stone to river stone

aids treatments, current and future (jon cohen)

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