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HIV/AIDS & TB

Peg Willingham
“Journalist to Journalist”
National Press Foundation
Mexico City, Mexico
July 30, 2008
AERAS GLOBAL TB VACCINE FOUNDATION

The HIV/AIDS Pandemic


The WHO estimates that in 2007:

• 33.2 million people living with HIV/AIDS.

• 2.5 million new HIV infections worldwide.

• 2.1 million people died from AIDS.


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The HIV/AIDS Pandemic

• HIV/AIDS is the world’s most deadly


infectious disease – killing more than 25
million people 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 2006:
– 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 (although most do not
develop disease)
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The Tuberculosis (TB) Pandemic


• TB is spread from
an infectious
person to a
vulnerable person
through the air

• TB usually
affects the lungs
(80% of cases)
but can affect any
part of an infected
person
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The Tuberculosis (TB) Pandemic

• TB is the world’s 2nd most deadly infectious disease in


adults, after HIV/AIDS, and one of leading causes of
death globally.

• TB is curable, but treatment is lengthy– often


spanning 6 months to a year – and is not available to
all.

• Drug-resistant TB is expensive, even more lengthy,


and difficult.
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Worldwide Distribution of New TB Cases, 2006


• New TB cases per 100,000 population in 2006

Estimated new TB
cases
(all forms) per 100 000
population
No estimate
0-24
25-49
50-99
100-299
300 or more
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What Drives TB Epidemic?


• Poverty, malnutrition, overcrowded living
conditions
– Global food crisis
– Slums – 1 billion and growing
• Smoking
• Diabetes
• HIV
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TB/HIV Coinfection
• TB is the leading cause of death PLWHA in Africa
and a major cause elsewhere

• TB is the most common presenting illness among


people living with HIV on ARV treatment worldwide

• 700,000 HIV positive TB patients globally in 2006;


85% in Sub-Saharan Africa

• 217,000 people died of HIV associated TB in 2006


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Estimated HIV prevalence in new TB


cases, 2006

HIV prevalence in
TB cases, (%)

No estimate
0–4
5–19
20–49
50 or more

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 2006. All rights reserved
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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 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, troublesome drug-drug interactions
(PLWHA on TB treatment cannot take nevirapine
or protease inhibitors)

• 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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“One Life, Two Diseases, One Response”


• Increasing awareness of need for coordinated
response
• World Health Organization - “Three I’s” -
– Infection control
– Isoniazid preventive therapy
– Intensified case finding
• Growing political commitment – e.g., Global
Leaders’ Forum at UN, 9 June 2008
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Drug-Resistant TB
• 450,00 new cases of MDR-TB (multi-drug
resistant) each year – TB resistant to at least
two first-line drugs (INH and RMP)
• XDR-TB (extensively drug-resistant) – TB
resistant to quinolones and second-line drugs
kanamycin, capreomycin, or amikacin
• XDR identified in 2006 after 52 HIV+ patients
died in Tugela Ferry, S. Africa
• XDR now identified in 45 countries (probably
present in many more)
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Drug-Resistant TB - Causes
• “Man-made” phenomenon – caused by missed
doses or incomplete treatment; made worse in
presence of HIV, poor infection control
• Drugs are relatively cheap, but not all are
always accessible, and all are over 40 years old
• Compliance issues – bulky tablets; taking on
empty stomach; feeling better and stopping
treatment
• Ineffective national TB control programs
• Prison overcrowding
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Drug-Resistant TB: Treatment


• Much more expensive, lengthy and difficult
– Minimum 18 months of treatment; toxicity, side
effects
– Isolation/hospitalization
– Surgery – last resort
– Costs up to 1400 times more than 1st-line treatment
• MDR-TB mortality rate comparable to lung
cancer (up to 80%)
• Some XDR strains virtually untreatable
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Turning the Tide:


New Tools to Combat TB

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 Drug Development
(TB Alliance) 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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Aeras Global TB Vaccine Foundation

Mission:

To develop new,
more effective TB
vaccines and
ensure their
affordability and
availability to all
who need them.
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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 by 2015
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Aeras Global Vaccine Development Partners


Industry Academia
GSK, Belgium Oxford University, UK
Crucell, Netherlands SATVI, South Africa
SSI, Denmark
Aeras St. Johns Nat’l Academy, India
Makerere University, Uganda
ImmunoBiology, UK Kenya Medical Research Institute, Kenya
Wuhan Biologicals, China Karolinska Institute, Sweden
Wuhan University, China
Serum Institute, India Albert Einstein College of Medicine, U.S.
Thymed, Germany Industry Academia Arizona State University, U.S.
Alphalyse, Denmark Biomedical Primate Research Center, The Netherlands
Case Western Reserve University, U.S.
Japan BCG Laboratory, Japan Central Institute for Tuberculosis, Russia
Korean Institute of TB, Korea Centre for International Health at the University of
Cyncron, Denmark Bergen, Norway
Cellestis, Australia
Foundations/ Colorado State University, U.S.
Emory University, U.S.
Immune Solutions, New Zealand Government Food and Drug Administration, U.S.
Larimer, U.S. FIND, Switzerland
Harvard University, U.S.
Sanofi Pasteur, France International AIDS Vaccine Initiative (IAVI)
Smittskyddsinstitutet, Sweden Foundations/Governments/NGOs Johns Hopkins University, U.S.
Bill & Melinda Gates Foundation, U.S. KNCV Tuberculosis Foundation, The Netherlands
Danish International Development Agency, DANIDA, Leiden University Medical Center, The Netherlands
Denmark Life Science Research Israel (LSRI), Israel
The Netherlands Ministry of Foreign Affairs, The Max Planck Institute for Infection Biology, Germany
Netherlands McGill University, Canada
National Center Institute, The Netherlands
Centers for Disease Control and Prevention (CDC), U.S.
New York University, U.S.
Fogarty International Center and NIAID, National Oregon Health Sciences University, U.S.
Institutes of Health, U.S. Public Health Research Institute
Research Council of Norway, Norway Stanford University, U.S.
European and Developing Countries Clinical Trials Partnership Saint Louis University., U.S.
(EDCTP), European Commission University of Bergen, Norway
LHL/ The Norwegian Association of Heart and Lung Patients, University of California-Davis, U.S.
Norway University of California- San Francisco, U.S.
Medicine in Need (MEND), U.S. University of Maryland, College Park, U.S.
STOP TB Partnership, Switzerland University of Wales, UK
TB-Alert, United Kingdom Vanderbilt University., U.S.
TBVI, Europe Walter Reed Army Institute of Research, U.S.
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Invention of BCG Vaccine


By Calmette & Guérin
1906-1921
No new TB Vaccine
in 87 years
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BCG Ineffective Against TB Pandemic

• Reduces risk of severe pediatric TB disease


• Unreliable protection when given to newborns
against adult pulmonary TB, which accounts
for most TB worldwide
• Despite wide use, BCG has had no apparent
impact on growing global TB epidemic
• Not known to protect against latent TB
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Potential of a New TB Vaccine


• Achieve substantial global TB control in 15-20
years
– If new vaccine regimen 50-70% better than BCGs
– In conjunction with better drugs and diagnostics
• Minimize TB as a global threat by 2050
– <1 case/million
– TB will be hard to eliminate without new, better
vaccines
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Potential Uses of a TB Vaccine


Exposure to infectious particles

Vaccine
prevention
No Infection (70%) of Infection (30%)
infectionPre-exposure: 10
Priming,
Boosting, Pre-exposure: 17
Vaccine Post-exposure – immunotherapy: 12
Prevention of Early Progression Vaccine prevention
Resistance
Acute and Early 1-2 years (5%) Of Latency
disease

Vaccine
Late Progression Resistance (95%)
Prevention of Lifetime (5%)
Reactivation
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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

24 Weeks
14 Weeks
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Booster Strategy for Adolescents


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Aeras’ TB Vaccine Candidates Under Development


Vaccine Source Stage Description
AERAS-407 Phase I Recombinant BCG
Aeras
rBCG 2009 Disease, Latency, Reactivation

Phase I
AERAS-402/
Crucell/Aeras South Africa Adeno 35 Vector
Crucell Ad35
USA
AERAS 485/Oxford Oxford/ISIS/Emergent Phase IIa/IIb
MVA Vector
MVA85A and Aeras South Africa
AERAS-405 Phase I
Aeras Nucleocapsid Vector
Shigella 2008
Phase I/IIa
GSK M72 GSK/Aeras Recombinant Protein
South Africa
sanofi pasteur/ Phase I
HyVac 4/
SSI/Intercell Sweden Recombinant Protein
AERAS-404
and Aeras Finland
April 2008
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Aeras Sponsored Field Sites


Palamaner
St Johns M. College Cambodian
India 2005 Health Committee
Cambodia, June
2008
Kisumu
KEMRI/CDC
Kenya 2006

Kampala
Makarere U.
Uganda 2006 Worcester
U. Cape Town
South Africa 1999
South Africa
• ~11,000 infant cohort study to determine efficacy of
BCG delivery routes completed in October 2006

• Enrollment completed for ~6,300 adolescent and


~4,800 infant cohort studies

• SATVI is currently conducting Phase I/II trials of 3 TB


vaccine candidates at site

• Most advanced site for large-scale TB vaccine trials


in the world
South Africa
• ~11,000 infant cohort study to determine efficacy of
BCG delivery routes completed in October 2006

• Enrollment completed for ~6,300 adolescent and


~4,800 infant cohort studies

• SATVI is currently conducting Phase I/II trials of 3 TB


vaccine candidates at site

• Most advanced site for large-scale TB vaccine trials


in the world
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SATVI/Aeras Clinical Trial Site


Worcester, South Africa
India
• Partnership with St. John’s National Academy
of Health Sciences

• Infrastructure set –up since 2005


– State-of-the-art immunology and mycobacteriology
laboratory, first of the kind in the area for TB diagnosis
– Highly skilled staff capable of performing the duties
necessary to maintain the infrastructure and execute
clinical research
– Residential and office facilities
– Professional Development Program (Gnana Jyothi –
“Light of Knowledge) in place since 2006
– Resource center established in 2006
India
• As of February 2008, 5,375
adolescents and 2,893 infants and
have been enrolled

• A total of ~ 8,300 participants are being


followed up for the occurrence of TB
Before After
Construction Construction
Residential Building
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Professional Development Program


A collaborative initiative to develop a
model program that builds and sustains
capacity of the clinical research staff.
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TB Vaccine Development Funding Needs


2006-15
Preclinical
development,
Discovery and $15M, 0%
translational Prepare clinical
research trial sites, $16M,
$1.38 bn 0%
38%
Vaccine
manufacturing/
scale-up, $217M,
6%
Clinical trials,
Maintaining BCG $457M, 13%
programmes
$1.49 bn Stop TB working
41% group, $69M, 2%

Total: $3.641 billion Global Plan to Stop TB, 2006-15


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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.
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Thank you!

Feel free to contact me with questions:

Peg Willingham
pwillingham@aeras.org
Website: www.aeras.org