HIV/AIDS & TB

Jerald C. Sadoff M.D.

“Journalist to Journalist”
National Press Foundation
Toronto, Canada
August 9th 2006
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The HIV/AIDS Pandemic

The World Health Organization (WHO)

estimates
that 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 infectious
person to a
vulnerable
person
through the air

TB usually
affects
the lungs
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, 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.
 Estimated new TB cases ('000s)

0
500
1000
1500
2000

India
China
Indonesia
Bangladesh
Nigeria
Pakistan
Philippines
South Africa
22 high-burdenAERAS

Russian Federation
Ethiopia
DR Congo
countries:

Viet Nam
Kenya
UR Tanzania
GLOBAL TB VACCINE

Brazil
Thailand
Myanmar
Zimbabwe
80% ofFOUNDATION

Uganda
Cambodia
Afghanistan
Mozambique
all new TB cases
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Highest TB rates per capita are in Africa

per 100 000 population

< 10
10 to 24
25 to 49
50 to 99
100 to 299
300 or more
No Estimate

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 Vaccines
Aeras 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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Invention of BCG Vaccine

By Calmette and
Guérin, 1906-
1921
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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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Variable Efficacy of BCG vs. Pulmonary TB

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

British School Children

BritishSchool
British SchoolChildren
Children
N. American Indians
USA (Chicago Infants)
Puerto Rico (Gen. Pop.)
S. India (Madanapalle)
USA (Georgia & Alabama)
S. India (Chingleput)
USA (Georgia Children)

Brazil (Sao Paolo)

Argentina (Buenos Aires)
Brazil (Belo Horizonte)
Cameroon (Yaounde)
Canada (Manitoba Indians)
Indonesia (Jakarta)
Surinam (Rangoon)
Sri Lanka (Colombo)
Colombia (Cali)
Argentina (Santa Fe)

Togo (Lome)
Thailand
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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

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

AERAS 403 Aeras Pre- Recombinant BCG which over

expresses antigens 85A, 85B
Clinical and 10.4, rvwith endosome
Phase I escape
Q2-07

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/Aeras Pre-clinical Replication deficient

adenovirus35 which expresses
Phase I antigens 85A, 85B, and 10.4
Q3-06) to boost rBCG

HyVac 4 SSI/Intercell Pre-clinical Recombinant Mtb antigens 85B

and 10.4 combined with
(AERAS 404) Aeras Phase I adjuvant IC31 to boost BCG
Q2 -07
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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
with
Sham, BCG
or rBCG30

Challenged with
Live aerosolized
TB

White arrows
point to
Granulomas
seen at sacrifice
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Humoral & Cellular Immunity

B - cell Will
Do we
CD4’s be
need a
Enough
balance
?
of CD4 &
CD8?

CD 4 CD 8
antibodies
T cell T cell

TH1 TH2 TH1 TH2 What

cytokine
IFN-γ TNF-α
DTP, Hib, Pneumococcus, profile
IL-2 IL-4 to we
Measles, Polio, Hep B,
Rotavirus, HPV, Malaria TB, Malaria, HIV need?
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Timeline Aeras 403 prime Aeras 402 boost

2006 2007 2008 2009 2010 2011 2012 2013 2014

Is it safe in 200-
Is it safe in 20- Is it safe in 6000-
600 subjects: Will it
40 subjects in 9000 infants &
infants & be
each age 10000-15000
adolescents ? used ?
group Adol ?
...
...
License, Launch
Phase Phase Phase III Infants &
I II
Phase III Adolescents Distribute

Does it
induce an Does it induce an Does it protect
immune immune response & against TB at a
response? show some protection? licensure standard ?
(Confidence for Ph III) Can you consistently
manufacture it?
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Global Plan 2006-2015 Resource Needs

Total needs by activities
•$31 billion gap
Diagnostics $0.5
ACSM $2.9
•$1 billion gap for
Vaccines $3.6
vaccines
• $187 M for scale up
Drugs $4.8
and manufacture
DOTS-Plus $5.8 DOTS Expansion
$32.0 •$341 M for clinical trials
TB/HIV $6.7

In $US billions
Global Plan to Stop TB 2006-2015, p. 59
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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.