Download Small pox 1520

Stopping HIV: what next?
Brian Williams
South African Centre for Epidemiological
Modelling and Analysis
http://public.me.com/williamsbg
The scale of the epidemic
Small pox AD 164-180
Killed 5 million in the Roman Empire
Small pox 1520
Killed half of all the Aztecs
Black Death (bubonic plague) 1347-1351
Killed 25 million in Europe
Influenza 1918
Killed 20 million people
HIV 1980 to …
40 million dead; 30 million infected; 20 million more in
the next ten years.
The scientific response
1981: CDC reports five deaths
1983: Virus is identified at the Institut Pasteur
1985: The full genome of the virus is sequenced
First ELISA test licensed
1987: AZT approved by the FDA
1996: Triple therapy available but costs $10,000/yr
2006: Cost of first line therapy reduced to $100/yr
2009: 22 drugs in 3 classes; 3 new classes under
development
Papers in peer-reviewed journals
Papers per year
5000
4000
3000
 100k papers ~ $20 billion
2000
1000
0
1980
1985
1990
1995
2000
2005
2010
PubMed: HIV & AIDS
Everyone is trying to help
Bill Gates
George Bush
Charlize Theron Carla Bruni
Bill Clinton
Bob Geldoff
Richard Gere
Funding
50
Projected need
US$ billions
40
30
“… the White House
estimates the cost of [the]
30,000-troop surge would be
about $30 billion per year”
(Forbes.com 2/12/2009)
Apollo
$145 billion
20
10
Previous funding
0
1980
1990
2000
Year
2010
2020
Cohen J. HIV/AIDS. The great funding surge. Science. 2008;321:512-9 and UNAIDS
Methods of control
Behavioural
Condoms
Have fewer partners
Delay sexual debut
Avoid inter-generational sex
Social
Mobilize communities
Reduce stigma
Support sex workers
Education and awareness
Empower women
Deal with migration
Biomedical
Treat STIs
Microbicides
Vaccines
Male circumcision
ART
40
Impact on HIV in the world
Prevalence (M)
30
20
$150 billion
25 years
100k papers
Great and the good
10
0
1980
1985
1990
1995
2000
2005
2010
1985
1990
1995
2000
2005
2010
Deaths (M/yr)
2
1
0
1980
www.unaids.org
Methods of control
Behavioural
Condoms
Have fewer partners
Delay sexual debut
Avoid inter-generational sex
Social
Mobilize communities
Reduce stigma
Support sex workers
Education and awareness
Empower women
Deal with migration
Biomedical
Treat STIs
Microbicides
Vaccines
Male circumcision
ART
HIV…
Initial doubling time in South Africa  1.5 years
Each HIV-positive person infects one other person
every 1.5 years (on average)
Life expectancy after infection  10 years
Each HIV positive person infects 10/1.5  7 people
Testing people once a year, start ART
immediately and assume that they are no
longer infectious, we will cut transmission by
10 times and (eventually) eliminate HIV
But: does ART really cut transmission?
Relative infectivity on ART
0.10
0.10
0.08
0.08
0.06
0.06
0.04
0.04
0.02
0.02
0.00
0.00
2.5
33
4
4.5
5.5
4
55
66
Log10(reduction in viral load)
3.5
6.5
Wawer, JID, 2005; Fideli, ARHR, 2001.
Mort.
0.010
0.05
0.00
1980
0.20
Off ART
2020
0.20
On ART
0.020
Prevalence
0.10
0.010
0.05
0.000
2000
0.00
1980
2040
0.15
0.00
1980
2020
Prevalence
0.010
0.05
0.000
2000
0.10
2040
0.000
2000
Off ART
2020
2040
On ART
0.020
0.15
0.10
0.010
0.05
0.00
1980
Incidence and mortality/yr
0.10
0.020
0.000
2000
2020
Mortality
HIV in South Africa: test and treat immediately
2040
Incidence and mortality/yr
Inc.
Incidence
0.15
Prevalence
0.020
Prevalence
Prevalence
0.15
0.20
Incidence and mortality/yr
Base line
Prev.
Incidence and mortality/yr
0.20
Current strategy
Universal access starting at CD4 = 200/µL
Mort.
0.010
0.05
0.00
1980
0.20
Off ART
2020
0.20
On ART
0.020
Prevalence
0.10
0.010
0.05
0.000
2000
0.00
1980
2040
0.15
0.00
1980
2020
Prevalence
0.010
0.05
0.000
2000
0.10
2040
0.000
2000
Off ART
2020
2040
On ART
0.020
0.15
0.10
0.010
0.05
0.00
1980
Incidence and mortality/yr
0.10
0.020
0.000
2000
2020
Mortality
HIV in South Africa: test and treat at 200/mL
2040
Incidence and mortality/yr
Inc.
Incidence
0.15
Prevalence
0.020
Prevalence
Prevalence
0.15
0.20
Incidence and mortality/yr
Base line
Prev.
Incidence and mortality/yr
0.20
David Ho: 1995
0.05
0.00
1980
0.20
0.010
9 M deaths
Off ART
2020
0.20
On ART
0.020
0.10
0.010
0.05
0.000
2000
2020
Prevalence
0.010
0.00
1980
2040
0.15
0.00
1980
0.10
0.05
0.000
2000
2040
0.020
0.000
2000
Off ART
2020
2040
On ART
0.020
0.15
0.10
0.062 M deaths
0.010
0.05
0.00
1980
Incidence and mortality/yr
Mort.
Prevalence
0.10
Incidence
0.15
Prevalence
Prevalence
Inc.
Incidence and mortality/yr
0.020
0.15
Prevalence
0.20
0.000
2000
2020
2040
Mortality
HIV in South Africa: test and treat immediately in 1998
Incidence and mortality/yr
Base line
Prev.
Incidence and mortality/yr
0.20
Assuming that this works what are the
possible problems?
•
•
•
•
Cost
Side effects
Resistance
Acceptability
US$ Billions/yr
What will it all cost?
8
6
Universal
testing
4
1% current GDP
< 350/mL
2
0
2000
2010
2020
2030
2040
2050
Year
Funding availability and needs
Blue and brown: 17% of current and projected global funding (UNAIDS)
Green: Universal testing; Red: < 350/µL
What is the cost of losing a life?
Cost to the state
 GNI/year x 30 years x Employment rate
 US$ 6,000 x 30 x 0.6
 US$ 100,000
10
US$ Billions/yr
5
0
2000
-5
2010
2020
2030
2040
2050
2% current GDP
-10
4% current GDP
-15
-20
-25
Net costs/savings
Blue and brown: 17% of current and projected global funding (UNAIDS)
Green: Universal testing; Red: < 350/µL
What about
side effects?
NRTI NNRTI PI FI
NRTI NNRTI PI FI
Drug resistance
Acquired
Transmitted
0.20
Phillips, AIDS, 2005
Hoffman, CID, 2009
Garcia-Gasco, JAC, 2008
“The wider use of regimens
that suppress viral
concentration to below
infectious levels is one of
several plausible
explanations for this
finding.”
Prevalence
Between 1% and 5%
per year
0.15
0.10
0.05
0.00
1996
1998
2000
2002
2004
Drug resistance (all forms)
Treatment naïve patients in the UK
Dunn, AIDS, 2007
Acceptability/Delivery
Navneet Garg | Global Business Manager | Vestergaard Frandse
In Kenya: 41,040 people tested in 1 week
Phase I: Pilot projects
•
•
•
•
•
•
•
•
•
•
Acceptability of testing
Acceptability of treatment
Compliance with treatment
Minimal side effects
Make sure that we do not create stigma
Check that we get viral-load suppression
Measure residual transmission
Check for viral rebound
Monitor drug resistance
Consider cost and delivery
Phase II: Randomized controlled trials or
step-wise interventions
Monitor all of the above outcomes but also
measure changes in incidence of HIV and TB at a
population level…
Phase III: Just do it

But ensure that we build in the best possible
monitoring and evaluation of all biomedical,
behavioural and psycho-social consequences
while using models to fully understand the
dynamics of the impact.
If one is caught in a dark maze it is better to
light a candle than to repeatedly walk into the
walls. Those [who] continue to dismiss
theoretical models, … seem concerned with
only the darkness and not the maze.
Ulanowicz 1988
Thank you