TB and HIV/AIDS (Peg Willingham)

TB & HIV/AIDS
Peg Willingham, Senior Director for External Affairs

Aeras Global TB Vaccine Foundation
JOURNALIST to JOURNALIST
Global Media Training Program on HIV/AIDS
Vienna, Austria
July 15, 2010
AERAS GLOBAL TB VACCINE FOUNDATION
The Tuberculosis 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
The TB Pandemic
• The World Health Organization (WHO)
estimates that in 2008:
– 9.4 million new cases of TB were
diagnosed
– 1.8 million people died from TB
• One out of three people in the world have

been infected with TB (although most do
not develop disease)
Estimated TB Incidence Rate, 2007
Estimated new TB cases (all

forms) per 100 000 population
No estimate
0-24
25-49
50-99
100-299
>= 300
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 2009. All rights reserved
The 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.
What Drives the TB Epidemic?

• Poverty
• Malnutrition
• Overcrowded living
conditions
– Slums – 1 billion and growing
• Smoking
• Diabetes
• HIV
HIV Prevalence Among TB Cases, 2007

imate: about 1.4 million TB/HIV cases and 450,000 TB/HIV death
HIV prevalence in
TB cases, (%)
No estimate
0–4
5–19
20–49 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.
>= 50 Dotted lines on maps represent approximate border lines for which there may not yet be full agreement.
 WHO 2009. All rights reserved
The HIV/AIDS Pandemic

UNAIDS and WHO estimate that in 2008:
• 33.4 million people living with HIV; 67%
in Sub-Saharan Africa
• 2.7 million new HIV infections worldwide
• 2 million AIDS-related deaths

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
deaths is linked to TB
HIV/AIDS and TB:
A Deadly Combination
One in four HIV

+
• HIV suppresses the human immune system

• TB suppresses the human immune system
• Each makes the other worse synergistically
• The number of new cases of TB has more than doubled in
countries with high HIV prevalence in the past 15 years
TB/HIV Co-infection
• 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
• 1.4 million of the new TB cases in 2008 were in people

living with HIV; 78% in the African Region
• 500,000 people died of HIV associated TB in 2008
+
TB Drug Resistance
• WHO estimates 490,000 MDR-TB cases emerge every
year, with more than 110,000 deaths
• Extensively drug-resistant (XDR) TB has been identified in

57 countries as of November 2009
• In 2008, WHO reported that the highest rates of MDR TB

ever recorded, with peaks of up to 22% of new TB cases,
were in some settings of the former Soviet Union. In the
same region, 1 in 10 cases of MDR-TB is XDR-TB
• Treatment for drug-resistant TB is much longer, more

complex and more expensive - with much lower success
rates
TB/HIV – A Human Rights Issue

• No vaccine to provide long-term protection from
pulmonary TB
• No HIV vaccine
• No benefit from biomedical advances for people and
communities affected by TB
• TB exposure due to inadequate health systems – poor
delivery of INH prophylaxis
• TB and HIV diagnostics inadequate for testing children
• Poor pediatric tracking programs to measure incidence
• Social circumstances lead to exposure – poverty,
malnutrition
Maternal TB/HIV important risk factor for

pediatric TB and mortality
• Estimated TB rate:
t risk factor for pediatric TB and mortality

-10 times higher in HIV-exposed
uninfected children <5 years than in
non-HIV exposed
-30 times higher in HIV-infected
children<5 years than non-HIV exposed
(Mukade 1997)
-1596/100,000 pop. HIV+ infants ≤ 12
on 2008; Gupta 2007)
mo. vs 65.9/100,000 pop. In HIV-infants
≤ 12 mo. (Hesseling CID 2009)
ita Gupta, July 19, 2009

Why do we need new tools for TB/HIV?

Diagnostics - More than 100 years old
• Particularly ineffective for diagnosing TB in people with
HIV/AIDS
• Newer, more effective methods are not widely used
• Tests for drug-resistant strains not widely available in the field
• Diagnostics suitable for community level still do not exist
Drugs - More than 40 years old

• Four drugs, taken for 6-9 months
• Not compatible with some HIV/AIDS antiretrovirals
• Treatment for resistant strains lengthy, expensive and toxic
with lower success rates
Vaccine - More than 85 years old

• Unreliable protection against pulmonary TB or past infancy
• Not safe for use in infants infected with HIV
Barriers to Research & Development

of New Tools
• Scientific uncertainty
• Market uncertainty
• Too much risk relative to perceived gain for

private sector
• Lack of clinical trial and manufacturing capacity

Addressing Barriers through

Product Development Partnerships (PDPs)
• Non-profit enterprises created to accelerate R&D for new products to
fight AIDS, TB, malaria and other neglected diseases
• Manage resources and partnerships from across public, private and
philanthropic sectors
• Complements partners expertise, facilities and capacity
• Utilize a portfolio management approach
• Act as a catalyst to advance new products through the development
pipeline towards registration and launch
• Range from “virtual” to “bricks and mortar” depending on availability
of external capacity
• Commitment to access, availability and affordability
New Tools: Target Product Profiles

• Drugs: new affordable TB drugs that will dramatically
shorten treatment time, work against drug-resistant TB,
be compatible with HIV antiretrovirals and improve
treatment of latent TB.
• Diagnostics: rapid, accurate and affordable TB tests and
point-of-care diagnostics to more efficiently detect TB and
drug-resistant forms of TB.
• Vaccines: new, safe, effective and affordable vaccine
regimens to protect against all forms of TB –MDR and
XDR, to prevent TB in children, adolescents and adults,
and to be safe for use in people infected with HIV
New Tools In the Pipeline

2015 and beyond:
3rd Wave of Innovation
2012 - 2015:
2nd Wave of Innovation
Available Now:
1st Wave of Innovation Holy grail diagnostic
Point of care diagnostic Significantly shorter (less

(detects resistance? than 2 months) TB
New diagnostic available Better for use in people
regimen
for peripheral lab settings with HIV?)
{specify}
New TB vaccine that will
New drug 4-month drug prevent all forms of TB in
New diagnostic available regimen which can be
all age groups and will be
for referral lab settings administered with ARVs safe for use in people
{specify} and is active against with HIV
drug-resistant TB
Diagnostics Pipeline
T
DS i al
e& erc ds
tur m
m etho
cul -co
p id Nonture m
Ra id on cul
Rapeciati
sp
First Referral Level 10-40%
*
D S T) NAAST)
T DST
AT ( v ed y
te d D etri c
% Access after 5
pro op
years
A a & ri m
lN Im icrosc Automction d colo l NAAT
an ua te p i a *
M m (de Ra Manu tion)*
te c
(de Peripheral Lab 70%
Distance from
est ) e AT
C t ion ictiv l NA
PO etect d
Patients
a
Pre I anu tion)
(d
LTBM etec
Community Health (d 95%
***
Care
2007 2008 2009 2010 2011 2012 2013 2014 2015 2016
Technologies in boxes: endorsed by
WHO
Abbreviations * Manual NAAT: technology for MTB Drug Susceptibility Testing (Line Probe Ass
DST: Drug Susceptibility Test
* * Manual NAAT: technology for MTB detection at the Peripheral Lab
NAAT: Nucleic Acid * * * Manual NAAT: technology for MTB detection at the Community Health Care L
Amplification Test
LTBI: Latent TB Infection
POC: Point of Care
Partner Sites for TB Diagnostic Trials

>50 trial sites in 25 countries
 18 sites in Africa, 19 in Asia, 7 in Americas, 8 in Europe

 Office in India and Uganda
 MOUs with >17 MOH & NTP
 Strong partnerships with international agencies
The Global Drug Portfolio

Testing combination regimens with multiple new drugs
Oflotub,
TDR
Bayer,
TB Alliance
J&J/Tibotec
Otsuka
Lupin
TB Alliance
Sequella
Pfizer
Phase I Phase II Phase III

TB Alliance Clinical Sites for New TB Drugs
Korea
China (3)
Delhi Taiwan
Mexico
Hong Kong
Malaysia Thailand (3)
Kenya
Tanzania (2)
Peru
Zambia
South Africa (5)

Global TB Vaccine Pipeline
AERAS402/Crucell Ad35
Crucell N.V./Aeras
MVA85A/AERAS-485
ing Group on New TB Vaccines
OETC/Aeras
Additional research at the discovery/early pre-clinical level: Bhagawan Mahavir Medical Research Center; Cardiff University; EpiVax, Inc.; ImmunoBiology Ltd.; Infectious Disease Research
Institute; Institute de Pharamacologie, Puso; Karolinska Institute; Malaysia-Finlay Institute, NIAID; NIH; Osaka University; Shanghai H&G Biotech; Sequella; UCLA; and, Vanderbilt University.
/UCT, South Africa
Makerere University, Uganda
KEMRI/CDC, Kenya
St John’s
Centre
anhica Health ResearchResearch
Mozambique Institute, India
Cambodian Health
Committee, Cambodia
Aeras Partnerships for Field Research

BCG introduced in 1921

Existing TB Vaccine Ineffective
• BCG unreliable against pulmonary TB,
which accounts for most TB disease
worldwide
• BCG is not know to protect against latent TB
• BCG is not recommended for use in infants

infected with HIV - increased risk for severe
BCG-related complications
• Despite wide use, BCG has had no apparent

impact on the growing global TB epidemic
• BCG does reduce risk of severe pediatric TB

disease, so it should continue to be used
until a better TB vaccine is available
Tuberculosis: TB Vaccine Too Dangerous

for Babies With AIDS Virus, Study Says
July 2, 2009 – The vaccine against tuberculosis that is
routinely given to 75 percent of the world’s infants is
too risky to give to those born infected with the AIDS
virus, says a new study published by the World Health
Organization. It recommended that vaccination be
delayed until babies can be tested.
WHO 2007 Recommendations on BCG
IV infected infants recently (2009) estimated

• Children with HIV infection
regardless of symptoms should not
be BCG vaccinated
• All high risk infants need HIV

screening
– Maternal antibody masks antibody
tests
– Detection of virus required
– Very difficult to implement in many
places
00 (Hesseling, et al)
Goals for Better TB Vaccines

• Eliminate TB as a public health
threat, in line with global targets
(<1 case/million), in conjunction
with new drugs and diagnostics
• Safe and effective in preventing
TB in children, adolescents and
adults, including people with
HIV (for whom BCG is unsafe)
• Protect against all forms of TB –
including MDR and XDR
Aeras Global TB Vaccine Foundation

Mission
To develop new, more effective TB
vaccines and ensure their availability to
all who need them
Method
• Collaborate with academic, biotech,
pharmaceutical and NGO partners to
develop and test new TB vaccines
• Purse a Prime-Boost strategy by
developing a modern replacement for
BCG plus booster vaccines
• Develop vaccines in its own lab and
manufacturing plant
Approach to a New TB Vaccine

• Improve BCG – make a
recombinant rBCG
• Prime-Boost regimen
• Give booster vaccinations in

infants
• Give booster vaccinations in

adolescents who have received
BCG at birth
Recombinant BCG (rBCG
• Safer in HIV infected infants or

others with immune-suppression
• BCG or rBCG boosted with another
TB vaccine is much better than
either vaccine alone
• Constructed to address each stage
of the TB life cycle
• Prevent infection and reactivation
• A new vaccine candidate with all of
these properties is expected to
enter clinical trials in 2010
Aeras TB Vaccine Candidates in Clinical Trials

Potential Boost Vaccines
SSI HyVac4 / AERAS-404 Status: Phase I
•Recombinant protein vaccine intended to be a booster vaccine
•Phase I clinical trials being conducted in Europe and Africa
GSK M72 Status: Phase II

•Recombinant protein vaccine intended to be a booster vaccine
•Phase I and II trials conducted in Europe, Africa and Asia, including a Phase I trial in HIV+ in
Europe
AERAS-402 / Crucell Ad35 Status: Phase IIb
•Viral vectored vaccine utilizing adenovirus 35; intended to be a booster vaccine
•Phase I and II trials conducted in North America and Africa; Phase IIb recently initiated in HIV+ in
S. Africa
MVA85A / AERAS-485 Status: Phase IIb
•Viral vectored vaccine utilizing modified vaccinia Ankara; intended to be a booster vaccine
•The most clinically-advanced booster vaccine for tuberculosis with an ongoing proof-of-concept
Phase IIb trial in infants
•Previous clinical trials in the UK and Africa, including in HIV+
•Awarded orphan drug status by EMEA
• All vaccine candidates found to have acceptable safety profiles
• All candidates induced CD4+ and/or CD8+ T-cell responses to TB antigens
• Immunogenicity results of booster candidates after BCG-priming are
encouraging for post-BCG prime-boost strategy
Clinical Trials Field Site Development

• Large-scale community-based clinical
trials are conducted in high burden
countries
• Aeras partners with local research

institutions to establish field sites and
conduct clinical research
• Build local infrastructure and health

care/research capacity to perform future
Good Clinical Practice (GCP) compliant
Phase III clinical trials
Example of Site Development

South Africa
• Partnership with South African Tuberculosis Vaccine Initiative (SATVI)
• Field site developed in Worcester (~120 km from Cape Town)
• Infrastructure developed:
– State-of-the-art immunology laboratory
– Highly skilled staff capable of performing the duties necessary to maintain the
infrastructure and execute clinical research
– Clinical and office facilities
– Professional Development Program (Siyantinga- “Reach for the Stars”) –
program initiated in 2001
– Resource Center established in 2005
Activities in South Africa - SATVI

Research Partner - South African Tuberculosis Vaccine
Initiative (SATVI)
• Conducting Phase I, II and IIb studies of four vaccine
candidates
• Adult and infant enrollment
• Over 230 staff trained since 2004
• Most advanced site for large-scale TB vaccine trials in the
world
• Future infant studies planned of AERAS-402/Crucell Ad35
• Western Cape
Activities in South Africa - UCT Lung Institute

Research Partner – University of
Cape Town Lung Institute
• Phase II clinical trial in adults with
active or previous TB (AERAS-
402/Crucell Ad35 )
• Cape Town
• Future study of TB vaccine
candidate in HIV infected adults
planned (part of multi-center
MVA85A/AERAS-485 study)
Activities in South Africa – Aurum Institute
Research Partner – Aurum Institute

• Enrolling adults with HIV in Phase IIb trial
• Safety and efficacy of TB vaccine (MVA85A/AERAS-485)
• Klerksdorp, North West (mining area)
Key Accomplishments at Other Partner Sites

• State-of-the-art immunology and
mycobacteriology laboratory established in
India
• Mycobacterial lab capacity is being augmented

in Kenya and Uganda
• Local staff trained in clinical research in

Kenya, Uganda and India
• Epidemiological cohort studies in Cambodia,

India, Kenya and Uganda
• Quality management and data management

infrastructure developed in India and Uganda
• Vaccine trials being conducted in Kenya

Local Benefits of Clinical Research

• Retain local talent and expertise
• Raise awareness about TB in the community
• Support and enhance local clinical research capacity
• Community health and education
• Infrastructure remains in the community
• Leverage investment in infrastructure to use for clinical trials of
other diseases
Access and Availability

• Future access considered at every stage of vaccine
development
• Manufacturing
– Guarantee by partners for sufficient production and affordable
prices, or technology transfer
– Manufactured by Aeras with partners in developing world
– Aeras will not consider vaccine candidates that will be costly to
manufacture on a large scale
• Pricing
– Dual pricing for affordable distribution in resource-poor countries
– Cost plus purchase from partner
– Aeras provides at cost
• Distribution
– Developing world governments
– International organizations (GAVI, UNICEF)
– Developing world partners
Building Manufacturing Capacity

• Reduce the cost and time to
manufacture and deliver vaccines to all
who need them
• Produce enough bulk doses of vaccine
to meet the world’s estimated need
• Work with partners in countries such
as India, China, Korea and South
Africa to produce, fill, finish and
distribute vaccines at the lowest
possible price
• Ensure uniformity of quality
• Minimize lag time between licensure
and distribution
Summary
• New TB vaccines, drugs and diagnostics
– will help achieve global development goals
– are critical to controlling TB pandemic
– will reduce the cost and burden of TB on patients, health care
systems and national economies
• PDPs are leading the effort to develop new TB tools that will be
affordable and accessible worldwide, engaging stakeholders from across
sectors toward common goals
• Research collaborations in TB endemic countries build and strengthen
research capacity, and are critical to advancing product candidates
• New tools need to be a global priority to help ensure rapid development
and distribution
Aeras gratefully acknowledges the support of

the following major donors
THE MARY LYNN
Netherlands Ministry of Foreign Affairs

RICHARDSON
FUND

TB and HIV/AIDS (Peg Willingham)

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TB and HIV/AIDS (Peg Willingham)

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TB & HIV/AIDS

Peg Willingham, Senior Director for External Affairs

The Tuberculosis Pandemic

• One out of three people in the world have

Estimated TB Incidence Rate, 2007

Estimated new TB cases (all

• TB is curable, but treatment is lengthy– often spanning

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

What Drives the TB Epidemic?

HIV Prevalence Among TB Cases, 2007

The HIV/AIDS Pandemic

• 2.7 million new HIV infections worldwide

• 2 million AIDS-related deaths

The HIV/AIDS Pandemic

• HIV/AIDS is the world’s most deadly

• Despite years of research, there is still

One in four HIV

• HIV suppresses the human immune system

• TB is the most common presenting illness among people

• 1.4 million of the new TB cases in 2008 were in people

• 500,000 people died of HIV associated TB in 2008

• Extensively drug-resistant (XDR) TB has been identified in

• In 2008, WHO reported that the highest rates of MDR TB

• Treatment for drug-resistant TB is much longer, more

TB/HIV – A Human Rights Issue

Maternal TB/HIV important risk factor for

t risk factor for pediatric TB and mortality

ita Gupta, July 19, 2009

Why do we need new tools for TB/HIV?

Drugs - More than 40 years old

Vaccine - More than 85 years old

Barriers to Research & Development

• Too much risk relative to perceived gain for

• Lack of clinical trial and manufacturing capacity

Addressing Barriers through

New Tools: Target Product Profiles

New Tools In the Pipeline

Point of care diagnostic Significantly shorter (less

Partner Sites for TB Diagnostic Trials

 18 sites in Africa, 19 in Asia, 7 in Americas, 8 in Europe

The Global Drug Portfolio

Phase I Phase II Phase III

TB Alliance Clinical Sites for New TB Drugs

South Africa (5)

Global TB Vaccine Pipeline

Makerere University, Uganda

Aeras Partnerships for Field Research

BCG introduced in 1921

• BCG is not know to protect against latent TB

• BCG is not recommended for use in infants

• Despite wide use, BCG has had no apparent

• BCG does reduce risk of severe pediatric TB

Tuberculosis: TB Vaccine Too Dangerous

WHO 2007 Recommendations on BCG

IV infected infants recently (2009) estimated

• All high risk infants need HIV

Goals for Better TB Vaccines

Aeras Global TB Vaccine Foundation

Approach to a New TB Vaccine

• Give booster vaccinations in

• Give booster vaccinations in

• Safer in HIV infected infants or

Aeras TB Vaccine Candidates in Clinical Trials