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HIV/AIDS & TB Jerald C. Sadoff M.D. “Journalist to Journalist” National Press Foundation Toronto, Canada August 9 th 2006
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HIV/AIDS & TB Jerald C. Sadoff M.D. “Journalist to Journalist” National Press Foundation Toronto, Canada August 9 th 2006.

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Page 1: HIV/AIDS & TB Jerald C. Sadoff M.D. “Journalist to Journalist” National Press Foundation Toronto, Canada August 9 th 2006.

HIV/AIDS & TBJerald C. Sadoff M.D.

“Journalist to Journalist”National Press Foundation

Toronto, CanadaAugust 9th 2006

Page 2: HIV/AIDS & TB Jerald C. Sadoff M.D. “Journalist to Journalist” National Press Foundation Toronto, Canada August 9 th 2006.

AERAS GLOBAL TB VACCINE FOUNDATION

The HIV/AIDS Pandemic

The World Health Organization (WHO) estimatesthat in 2005:

– 40.3 million people were living with HIV– 4.9 million people were newly infected with HIV– 3.1 million people died of AIDS

Page 3: HIV/AIDS & TB Jerald C. Sadoff M.D. “Journalist to Journalist” National Press Foundation Toronto, Canada August 9 th 2006.

AERAS GLOBAL TB VACCINE FOUNDATION

The HIV/AIDS Pandemic

• AIDS is the world’s most deadly infectious disease – more than 25 million people have died as a result of AIDS since the disease was first recognized in 1981

• Despite years of research, there is still no cure or vaccine for HIV/AIDS

Page 4: HIV/AIDS & TB Jerald C. Sadoff M.D. “Journalist to Journalist” National Press Foundation Toronto, Canada August 9 th 2006.

AERAS GLOBAL TB VACCINE FOUNDATION

The Tuberculosis (TB) Pandemic

The World Health Organization (WHO) estimates that in 2004:

– 8.9 million new cases of TB were diagnosed– 1.7 million people died from TB– One out of three people in the world have been

infected with TB (most do not develop disease)

Page 5: HIV/AIDS & TB Jerald C. Sadoff M.D. “Journalist to Journalist” National Press Foundation Toronto, Canada August 9 th 2006.

AERAS GLOBAL TB VACCINE FOUNDATION

The Tuberculosis (TB) Pandemic

TB is spread from an infectiousperson to avulnerable personthrough the air

TB usually affectsthe lungsbut can affectany part of an infected person

Page 6: HIV/AIDS & TB Jerald C. Sadoff M.D. “Journalist to Journalist” National Press Foundation Toronto, Canada August 9 th 2006.

AERAS GLOBAL TB VACCINE FOUNDATION

The Tuberculosis (TB) Pandemic

• TB is the world’s 2nd most deadly infectious disease, after AIDS

• Although TB is curable, treatment is lengthy and costly– often spanning 6 months to a year – and is not easily accessible to all who need it.

Page 7: HIV/AIDS & TB Jerald C. Sadoff M.D. “Journalist to Journalist” National Press Foundation Toronto, Canada August 9 th 2006.

AERAS GLOBAL TB VACCINE FOUNDATION22 high-burden countries: 80% of all new TB cases

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Page 8: HIV/AIDS & TB Jerald C. Sadoff M.D. “Journalist to Journalist” National Press Foundation Toronto, Canada August 9 th 2006.

AERAS GLOBAL TB VACCINE FOUNDATION

Highest TB rates per capita are in Africa

25 to 49

50 to 99

100 to 299

< 10

10 to 24

300 or more

No Estimate

per 100 000 population

The boundaries and names shown and the designations used on this map do not imply the expression of any opinion whatsoever on the part of the World Health Organization concerning the legal status of any country, territory, city or area or of its authorities, or concerning the delimitation of its frontiers or boundaries. Dotted lines on maps represent approximate border lines for which there may not yet be full agreement.

© WHO 2002

Page 9: HIV/AIDS & TB Jerald C. Sadoff M.D. “Journalist to Journalist” National Press Foundation Toronto, Canada August 9 th 2006.

AERAS GLOBAL TB VACCINE FOUNDATION

HIV/AIDS and TB: A Deadly Combination

• HIV suppresses the human immune system

• TB suppresses the human immune system

• Each makes the other worse synergistically

Page 10: HIV/AIDS & TB Jerald C. Sadoff M.D. “Journalist to Journalist” National Press Foundation Toronto, Canada August 9 th 2006.

AERAS GLOBAL TB VACCINE FOUNDATION

HIV/AIDS and TB: A Deadly Combination

• 12 million people worldwide are co-infected with TB and HIV

• TB is the leading cause of death of HIV positive people. In fact, TB accelerates progression of HIV into AIDS

• People with HIV/AIDS are highly susceptible to TB disease – 50-100 times more so than people without HIV

Page 11: HIV/AIDS & TB Jerald C. Sadoff M.D. “Journalist to Journalist” National Press Foundation Toronto, Canada August 9 th 2006.

AERAS GLOBAL TB VACCINE FOUNDATION

HIV/AIDS and TB Co-Epidemic

• TB is hard to diagnose with the standard “sputum smear” test in people with HIV/AIDS

• Both TB and HIV drugs work in co-infected people, but, treating HIV and TB co-infection is complicated as there are troublesome drug-drug interactions

• Without proper treatment, 90% of HIV positive people die of TB within months of TB appearance

Page 12: HIV/AIDS & TB Jerald C. Sadoff M.D. “Journalist to Journalist” National Press Foundation Toronto, Canada August 9 th 2006.

AERAS GLOBAL TB VACCINE FOUNDATION

HIV/AIDS and TB Co-Epidemic

• Women of reproductive age are highly susceptible to TB disease and bear a very heavy burden of the HIV/AIDS and TB co-epidemic

• Access to care and treatment is least available in the developing world – where the co-epidemic is greatest

Page 13: HIV/AIDS & TB Jerald C. Sadoff M.D. “Journalist to Journalist” National Press Foundation Toronto, Canada August 9 th 2006.

AERAS GLOBAL TB VACCINE FOUNDATION

Turning the Tide: New Tools to Combat TB by PDPs

New Diagnostics– FIND (Foundation for Innovative New

Diagnostics) is focused on the development of rapid, accurate and affordable diagnostic tests to improve detection of TB

– This is a critical need for PLWHA who are co-infected with TB

Page 14: HIV/AIDS & TB Jerald C. Sadoff M.D. “Journalist to Journalist” National Press Foundation Toronto, Canada August 9 th 2006.

AERAS GLOBAL TB VACCINE FOUNDATION

Turning the Tide: New Tools to Combat TB by PDPs

New Treatments– The Global Alliance for TB Drugs is working

to develop new, faster-acting and affordable TB medicines

– The Consortium to Respond Effectively to the TB AIDS Epidemic (CREATE) is seeking ways to prevent TB disease in people living with HIV/AIDS

Page 15: HIV/AIDS & TB Jerald C. Sadoff M.D. “Journalist to Journalist” National Press Foundation Toronto, Canada August 9 th 2006.

AERAS GLOBAL TB VACCINE FOUNDATION

Turning the Tide: New Tools to Combat TB by PDPs

New VaccinesAeras Global TB Vaccine Foundation is working to develop a new, more effective TB vaccine – the first new vaccine in over 80 years

Page 16: HIV/AIDS & TB Jerald C. Sadoff M.D. “Journalist to Journalist” National Press Foundation Toronto, Canada August 9 th 2006.

AERAS GLOBAL TB VACCINE FOUNDATION

Developing a New TB Vaccine

Goals of the Aeras Global TB Vaccine Foundation: - To obtain regulatory approval and ensure supply of a new TB vaccine regimen within 7-10 years- To introduce 2nd generation vaccines with improved product profiles and efficacy against latent TB in 9-15 years

Page 17: HIV/AIDS & TB Jerald C. Sadoff M.D. “Journalist to Journalist” National Press Foundation Toronto, Canada August 9 th 2006.

AERAS GLOBAL TB VACCINE FOUNDATION

Page 18: HIV/AIDS & TB Jerald C. Sadoff M.D. “Journalist to Journalist” National Press Foundation Toronto, Canada August 9 th 2006.

AERAS GLOBAL TB VACCINE FOUNDATION

By Calmette and Guérin, 1906-1921

Invention of BCG Vaccine

Page 19: HIV/AIDS & TB Jerald C. Sadoff M.D. “Journalist to Journalist” National Press Foundation Toronto, Canada August 9 th 2006.

AERAS GLOBAL TB VACCINE FOUNDATION

No New TB Vaccine in 85 Years

BCG developed in 1921

Page 20: HIV/AIDS & TB Jerald C. Sadoff M.D. “Journalist to Journalist” National Press Foundation Toronto, Canada August 9 th 2006.

AERAS GLOBAL TB VACCINE FOUNDATION

Developing a New TB Vaccine

• BCG is the most widely used vaccine in the world - and not highly effective

• BCH may provide ~70% protection against severe TB in young children, so it will continue to be used until something better is available

• BCG provides little protection against childhood pulmonary TB and it is questionable if any protection later in life when it is given to infants

Page 21: HIV/AIDS & TB Jerald C. Sadoff M.D. “Journalist to Journalist” National Press Foundation Toronto, Canada August 9 th 2006.

AERAS GLOBAL TB VACCINE FOUNDATION

British School ChildrenBritish School Children

Variable Efficacy of BCG vs. Pulmonary TB

British School Children

S. India (Madanapalle)USA (Georgia & Alabama)S. India (Chingleput)USA (Georgia Children)

USA (Chicago Infants)Puerto Rico (Gen. Pop.)

N. American Indians

Brazil (Sao Paolo)Argentina (Buenos Aires)Brazil (Belo Horizonte)Cameroon (Yaounde) Canada (Manitoba Indians)

Surinam (Rangoon)Sri Lanka (Colombo)Colombia (Cali)Argentina (Santa Fe)

Togo (Lome)

Thailand

Indonesia (Jakarta)

Vaccine Efficacy (%)-900 -500 -300 -100 0 20 40 60 70 80 90 Population

Page 22: HIV/AIDS & TB Jerald C. Sadoff M.D. “Journalist to Journalist” National Press Foundation Toronto, Canada August 9 th 2006.

AERAS GLOBAL TB VACCINE FOUNDATION

Developing a New TB Vaccine

• Vaccines with a 50 – 90% efficacy rate could eliminate about 1/3 of TB disease and death

• Effective vaccines in combination with better diagnostics and antibiotics could:• achieve global control of TB • eliminate TB by 2050 (<1 case/million)

• A 75% effective vaccine is estimated to save $25 billion in medical costs worldwide

Page 23: HIV/AIDS & TB Jerald C. Sadoff M.D. “Journalist to Journalist” National Press Foundation Toronto, Canada August 9 th 2006.

AERAS GLOBAL TB VACCINE FOUNDATION

Advantages of BCG as basis for a new, improved TB vaccine

• BCG can be given at birth • Can be administered orally• >3 billion doses administered• <0.2/106 serious

complications• Persists innocuously in vivo

Page 24: HIV/AIDS & TB Jerald C. Sadoff M.D. “Journalist to Journalist” National Press Foundation Toronto, Canada August 9 th 2006.

AERAS GLOBAL TB VACCINE FOUNDATION

Approach to a New TB Vaccine

• Improve BCG – make a recombinant rBCG

• Give booster vaccinations in infants

• Give booster vaccinations in adolescents who have received BCG at birth

Page 25: HIV/AIDS & TB Jerald C. Sadoff M.D. “Journalist to Journalist” National Press Foundation Toronto, Canada August 9 th 2006.

AERAS GLOBAL TB VACCINE FOUNDATION

Prime Boost Strategy for Infants

14 Weeks

24 Weeks

Page 26: HIV/AIDS & TB Jerald C. Sadoff M.D. “Journalist to Journalist” National Press Foundation Toronto, Canada August 9 th 2006.

AERAS GLOBAL TB VACCINE FOUNDATION

Booster Strategy for Adolescents

Page 27: HIV/AIDS & TB Jerald C. Sadoff M.D. “Journalist to Journalist” National Press Foundation Toronto, Canada August 9 th 2006.

AERAS GLOBAL TB VACCINE FOUNDATION

Aeras’ TB Vaccine Candidates Under DevelopmentVaccine Source Stage Description

rBCG30 UCLA/Aeras Phase I Recombinant BCG genetically modified to over express antigen 85B

AERAS 403 AerasPre-Clinical

Phase IQ2-07

Recombinant BCG which over expresses antigens 85A, 85B and 10.4, rvwith

endosome escape

M72 Aeras/GSK Phase I

Fusion molecule comprised of a protein from the PPE family (Rv1196), combined with

an inactive serine protease Rv0125 to boost BCG

AERAS 402 Crucell/AerasPre-clinical

Phase IQ3-06)

Replication deficient adenovirus35 which expresses antigens 85A, 85B, and 10.4 to

boost rBCG

HyVac 4(AERAS 404)

SSI/Intercell Aeras

Pre-clinicalPhase IQ2 -07

Recombinant Mtb antigens 85B and 10.4 combined with adjuvant IC31 to boost

BCG

AERAS X05 AerasPre-clinicalPhI Q2-07

Mtb antigens delivered by RNA capsid system to boost rBCG

Page 28: HIV/AIDS & TB Jerald C. Sadoff M.D. “Journalist to Journalist” National Press Foundation Toronto, Canada August 9 th 2006.

AERAS GLOBAL TB VACCINE FOUNDATION

Proving New TB Vaccines Work

• Animal Challenge Models• Human immune responses• Clinical Trials

Page 29: HIV/AIDS & TB Jerald C. Sadoff M.D. “Journalist to Journalist” National Press Foundation Toronto, Canada August 9 th 2006.

AERAS GLOBAL TB VACCINE FOUNDATION

rBCG better then BCG in Guinea pig

Protection

Guinea pigs Vaccinated

withSham, BCGor rBCG30

Challenged withLive aerosolized

TB

White arrowspoint to

Granulomas seen at sacrifice

Page 30: HIV/AIDS & TB Jerald C. Sadoff M.D. “Journalist to Journalist” National Press Foundation Toronto, Canada August 9 th 2006.

AERAS GLOBAL TB VACCINE FOUNDATION

CD 4 T cell

CD 8 T cell

TH1 TH2 TH1 TH2

IFN-γ

IL-2

TNF-α

IL-4

B - cell

antibodies

DTP, Hib, Pneumococcus, Measles, Polio, Hep B,

Rotavirus, HPV, Malaria

Humoral & Cellular Immunity

TB, Malaria, HIV

Will CD4’s

beEnough

?

Do we need a balance of CD4 & CD8?

What cytokine profile

to we need?

Page 31: HIV/AIDS & TB Jerald C. Sadoff M.D. “Journalist to Journalist” National Press Foundation Toronto, Canada August 9 th 2006.

AERAS GLOBAL TB VACCINE FOUNDATION

2011 2012 2013 2014

Phase III InfantsPhase III Adolescents

2006 2007 2008 2009 2010

License, Launch &

Distribute

Timeline Aeras 403 prime Aeras 402 boost

Phase I

Is it safe in 20-40 subjects in

each age group

. . .

PhaseII

Does it induce an immune

response?

Is it safe in 200-600 subjects:

infants & adolescents ?

. . .

Does it induce an immune response &

show some protection?(Confidence for Ph III)

Is it safe in 6000-9000 infants &

10000-15000 Adol ?

Does it protect against TB at a

licensure standard ?Can you consistently

manufacture it?

Will it be

used ?

Page 32: HIV/AIDS & TB Jerald C. Sadoff M.D. “Journalist to Journalist” National Press Foundation Toronto, Canada August 9 th 2006.

AERAS GLOBAL TB VACCINE FOUNDATION

Global Plan 2006-2015 Resource Needs

•$31 billion gap•$1 billion gap for vaccines• $187 M for scale up and manufacture•$341 M for clinical trials

In $US billions

Total needs by activities

Global Plan to Stop TB 2006-2015, p. 59

Vaccines $3.6

Drugs $4.8

DOTS-Plus $5.8 DOTS Expansion $32.0

Diagnostics $0.5

TB/HIV $6.7

ACSM $2.9

Page 33: HIV/AIDS & TB Jerald C. Sadoff M.D. “Journalist to Journalist” National Press Foundation Toronto, Canada August 9 th 2006.

AERAS GLOBAL TB VACCINE FOUNDATION

Resources Needed

• Additional funding to support research, planning and product development for new tools

• More research and clinical trials to demonstrate whether new tools are effective and appropriate

Page 34: HIV/AIDS & TB Jerald C. Sadoff M.D. “Journalist to Journalist” National Press Foundation Toronto, Canada August 9 th 2006.

AERAS GLOBAL TB VACCINE FOUNDATION

Resources Needed

• Policies to guarantee that people in developing countries can afford the tools and regulatory processes to ensure quality

• Successful partnerships among private corporations, the global health community, and governments of affected nations

Page 35: HIV/AIDS & TB Jerald C. Sadoff M.D. “Journalist to Journalist” National Press Foundation Toronto, Canada August 9 th 2006.

AERAS GLOBAL TB VACCINE FOUNDATION

Summary

• TB and HIV/AIDS are terrible pandemics in and of themselves – together they are deadly

• Vaccines that are safe and effective used with new diagnostics and drugs are the only way to control HIV and TB

• Without vaccines HIV and TB will not be controlled• A TB vaccine would prevent undue suffering and

death among those at high risk, and would save billions of dollars in health costs.