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 164-180Killed 5 million in the Roman Empire

Small pox 1520Killed half of all the Aztecs

Black Death (bubonic plague) 1347-1351Killed 25 million in Europe

Influenza 1918Killed 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

0

1000

2000

3000

4000

5000

1980 1985 1990 1995 2000 2005 2010

100k papers ~ $20 billion

PubMed: HIV & AIDS

Pap

ers

per

year

Everyone is trying to help

Bill Gates

Bob Geldoff

George Bush

Charlize Theron Richard Gere

Bill Clinton

Carla Bruni

0

10

20

30

40

50

1980 1990 2000 2010 2020Year

Funding

Cohen J. HIV/AIDS. The great funding surge. Science. 2008;321:512-9 and UNAIDS

US

$ bi

llion

s

Previous funding

Projected need

“… 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

Methods of controlBehaviouralCondomsHave fewer partnersDelay sexual debutAvoid inter-generational sex

SocialMobilize communitiesReduce stigmaSupport sex workersEducation and awarenessEmpower womenDeal with migration

BiomedicalTreat STIsMicrobicidesVaccinesMale circumcision ART

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40

1980 1985 1990 1995 2000 2005 2010

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1980 1985 1990 1995 2000 2005 2010

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1

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1980 1985 1990 1995 2000 2005 2010

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1

2

1980 1985 1990 1995 2000 2005 2010

De

ath

s (M

/yr)

Pre

vale

nce

(M

)

Impact on HIV in the world

www.unaids.org

$150 billion25 years100k papersGreat and the good

Methods of controlBehaviouralCondomsHave fewer partnersDelay sexual debutAvoid inter-generational sex

SocialMobilize communitiesReduce stigmaSupport sex workersEducation and awarenessEmpower womenDeal with migration

BiomedicalTreat STIsMicrobicidesVaccinesMale circumcision ARTMale 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

0.00

0.02

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But: does ART really cut transmission?

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Rel

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Wawer, JID, 2005; Fideli, ARHR, 2001.

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Prevalence

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Off ART On ART

Mortality

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HIV in South Africa: test and treat immediately

Prev.

Inc.

Mort.

Current strategy

Universal access starting at CD4 = 200/µL

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Mortality

Off ART On ART

HIV in South Africa: test and treat at 200/L

Prev.

Inc.

Mort.

David Ho: 1995

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ality

/yr

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Mortality

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1980 2000 2020 2040

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Base line

0.062 M deaths

9 M deaths0.00

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Prevalence

Off ART On ART

HIV in South Africa: test and treat immediately in 1998

Prev.

Inc.

Mort.

Assuming that this works what are the possible problems?

• Cost• Side effects• Resistance• Acceptability

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2000 2010 2020 2030 2040 2050Year

Funding availability and needsBlue and brown: 17% of current and projected global funding (UNAIDS)

Green: Universal testing; Red: < 350/µL

US

$ B

illio

ns/y

r

1% current GDP

Universal testing

< 350/L

What will it all cost?

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

-25

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-15

-10

-5

0

5

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2000 2010 2020 2030 2040 2050

US

$ B

illio

ns/y

r

2% current GDP

4% current GDP

Net costs/savingsBlue and brown: 17% of current and projected global funding (UNAIDS)

Green: Universal testing; Red: < 350/µL

NRTI NNRTI PI FI

What aboutside effects?

NRTI NNRTI PI FI

Drug resistance

Acquired

Between 1% and 5% per year

Phillips, AIDS, 2005Hoffman, CID, 2009

Garcia-Gasco, JAC, 2008

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1996 1998 2000 2002 2004

Transmitted

Pre

vale

nce

Drug resistance (all forms) Treatment naïve patients in the UK

Dunn, AIDS, 2007

“The wider use of regimens that suppress viral concentration to below infectious levels is one of several plausible explanations for this finding.”

Navneet Garg | Global Business Manager | Vestergaard Frandsen

In Kenya: 41,040 people tested in 1 week

Acceptability/Delivery

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