hiv/aids and tb (dr. jerald sadoff)
TRANSCRIPT
HIV/AIDS & TBJerald C. Sadoff M.D.
“Journalist to Journalist”National Press Foundation
Toronto, CanadaAugust 9th 2006
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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
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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
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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)
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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
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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.
AERAS GLOBAL TB VACCINE FOUNDATION22 high-burden countries: 80% of all new TB cases
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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
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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
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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
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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
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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
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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
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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
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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
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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
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By Calmette and Guérin, 1906-1921
Invention of BCG Vaccine
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No New TB Vaccine in 85 Years
BCG developed in 1921
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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
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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
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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
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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
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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
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Prime Boost Strategy for Infants
14 Weeks
24 Weeks
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Booster Strategy for Adolescents
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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
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Proving New TB Vaccines Work
• Animal Challenge Models• Human immune responses• Clinical Trials
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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
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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?
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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 ?
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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
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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
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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
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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.