Type of Review: Annual Review
Project Title: International AIDS Vaccine Initiative (IAVI)
Date started: August 2013
Date review undertaken: June 2014
Instructions to help complete this template:
Before commencing the annual review you should have to hand:
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the Business Case or earlier project documentation.
the Logframe
the detailed guidance (How to Note)- Reviewing and Scoring Projects
the most recent annual review (where appropriate) and other related monitoring reports
key data from ARIES, including the risk rating
the separate project scoring calculation sheet (pending access to ARIES)
You should assess and rate the individual outputs using the following rating scale and
description. ARIES and the separate project scoring calculation sheet will calculate the overall
output score taking account of the weightings and individual outputs scores:
Description
Outputs substantially exceeded expectation
Outputs moderately exceeded expectation
Outputs met expectation
Outputs moderately did not meet expectation
Outputs substantially did not meet expectation
Scale
A++
A+
A
B
C
Introduction and Context
What support is the UK providing?
DFID will provide £5,050,000 over the period 2013-14 to 2017-18 to the International AIDS
Vaccine Initiative (IAVI), to support the development of new vaccines to prevent HIV infection.
What are the expected results?
The long term impact of the programme is to improve health and save lives through the
potential availability of safe, effective, accessible, preventive AIDS vaccines for use throughout
the world, especially in developing countries most affected by AIDS, as part of a comprehensive
& sustainable response to ending the AIDS pandemic. The shorter term outcome is to stimulate
significant advances in the AIDS vaccine field that harness partnerships to expand the number,
quality & diversity of AIDS vaccine candidates in the clinical pipeline
The outputs of the programme will deliver high quality and cutting edge research that will
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improve our understanding of the development of new technologies for prevention of HIV:
1. Vaccine candidates that elicit broadly neutralising antibodies (bNAbs) against HIV
designed
2. Selected Replicating Viral Vector-based HIV vaccine candidates advanced to clinical
testing
3. Clinical pipeline of HIV vaccine candidates expanded
4. Clinical research capacity in developing countries sustained and strengthened
What is the context in which UK support is provided?
There are currently 34 million people living with HIV and AIDS. The burden of HIV and AIDS
has disproportionately impacted women and girls, is a leading cause of death for women of
reproductive age worldwide — and in sub-Saharan Africa, where the epidemic has hit hardest,
women ages 15–24 are at least twice as likely to be infected with HIV as young men.
Antiretroviral therapy (ART) is now available for those living with AIDS, but there are 5 new
HIV infections for every 3 people starting on ART. ART means more people are living longer,
but the cost of life-long treatment and care is arguably unsustainable; particularly as more
people access treatment and drug resistance increases. A vaccine for HIV could lower health
care costs and disease burden and support poverty alleviation. An effective vaccine also has
the potential to further reduce mother-to-child transmission of HIV, and reduce maternal
deaths. Modelling suggest that return on investment for AIDS vaccine R&D is high, even a
partially-effective vaccine could save £8.9bn - £18.5bn in averted antiretroviral costs over 10
years.
There are acknowledged market failures around the development of new technologies for
diseases of poverty. The lack of commercial return from HIV prevention technologies
(including vaccines and microbicides) for the poorest is a stumbling block that has stopped the
pharmaceutical industry from undertaking product development research single-handedly.
This challenge can be overcome by sharing costs and risks with research partners. Product
Development Partnerships (PDPs) are non-profit entities that act as virtual pharmaceutical
companies, coordinating the development of new products and drawing upon the respective
strengths of academia, large and small industry at different stages of the R&D and
commercialisation process. PDPs are effectively a ‘one stop shop’ for product development–
forming partnerships from early discovery of potential new products to the access and delivery
of finished products
Section A: Detailed Output Scoring
Output 1: Vaccine candidates that elicit broadly neutralising antibodies (bNAbs) against HIV
designed
Output 1 score and performance description: A – Output met expectations
Progress against expected results:
Indicators in the logframe
 Number of HIV envelope immunogens screened in animal or other validated models
per year. Milestone of at least 3 immunogens screened by Dec 2014.
 Number of HIV envelope immunogens advanced to early development. Milestone of 1
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HIV envelope immunogen advanced to early development by December 2014.
Number of HIV envelope immunogens tested in exploratory clinical trials. Milestone of
at least 1 HIV envelope immunogen in exploratory clinical trials by December 2016.
IAVI is on track to meet these milestones. During the reporting period (2013), two HIV
envelope immunogens were screened and multiple immunogens are being screened and at
least 3 will be screened in the current year. Work is ongoing on the early development of two
immunogens and a third will be selected by the end of 2014. IAVI has entered early
development of the lead candidate, which will lead to manufacture and initiation of exploratory
clinical trials during 2015.
Product development research is a long-term and complex process. There are many stages
from discovering potential vaccine candidates (in this case HIV envelope immunogens), early
screening in animal models, early testing in humans, long-term large-scale testing in humans).
HIV vaccine science has proven to be far more complex than was initially envisaged. IAVI and
partners have played an important role in the development of both theory and discovery of
broadly neutralising antibodies as a potential mechanism for vaccine development.
The work is progressing as planned, but there is a high risk of failure and any one potential
candidate can fail at any stage along the development pathway. Therefore it is not possible to
say whether any of the candidates will progress to becoming a viable vaccine.
Recommendations:
No recommendations appropriate at this stage.
Impact Weighting (%): 35%
Revised since last Annual Review? No
Risk: High
Revised since last Annual Review? No
Output 2: Selected Replicating Viral Vector-based HIV vaccine candidates advanced to
clinical testing
Output 2 score and performance description: A – output met expectations
Progress against expected results:
Indicator in the logframe
 Number of replicating viral vector based vaccine candidates advanced to preclinical
development. Milestone of at least 1 replicating vector vaccine from IAVI's portfolio met
criteria to advance to clinical development by December 2015
During the reporting period (2013) there were a number of replicating viral vector candidates in
varying stages of preclinical development. One viral vector clinical trial (the Sendai trial) was
initiated and the trial started to enrol patients earlier than anticipated.
As discussed above under Output 1, product development research is a long-term and
complex process and it is not possible to say whether any of the candidates will progress to
becoming a viable vaccine. The candidates in the pipeline are progressing as anticipated at
this time. Go/No-Go decisions for these candidates will be made in mid 2015, to whether
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either of the 2 additional candidates meet the criteria to advance to clinical development, or
whether IAVI will seek alternative partnerships to ensure a lead candidate enters the clinical
pipeline by December 2015.
IAVI’s current portfolio has four viral vectors which have been selected for further study:
Sendai, Canine Distemper Virus (CDV), vesicular stomatitis virus (VSV), and Cytomegalovirus
(CMV). Two additional candidates also met predetermined criteria for further preclinical
development and may be taken forward in the future.
Recommendations:
No recommendations appropriate at this stage.
Impact Weighting (%): 25%
Revised since last Annual Review? No
Risk: High
Revised since last Annual Review? No
Output 3: Clinical pipeline of HIV vaccine candidates expanded
Output 3 score and performance description: A –output met expectations
Progress against expected results:
Indicators in the logframe
 Number of active Phase I/II clinical trials. Milestone is that the current 3 active Phase
I/II trials are evaluated in go/no-go decision (to progress to late stage development) by
December 2015.
 Number of active HIV vaccine efficacy trials. Milestone is at least 1 HIV vaccine
efficacy trial initiated by December 2016.
These logframe indicators refer to work that will happen during 2015, based on IAVI’s current
portfolio of three active Phase I/II trials. These trials are on track and should reach go/no-go
decision points as planned, by December 2015. If a ‘go decision’ is made for any of the three
vaccine candidates, then they will progress to efficacy trials.
This work is on track to reach the key decision points during 2015.
Recommendations:
No recommendations appropriate at this stage.
Impact Weighting (%): 25%
Revised since last Annual Review? No
Risk: High
Revised since last Annual Review? No
Output 4: Clinical research capacity in developing countries sustained and strengthened
Output 4 score and performance description: A – Output met expectations
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Progress against expected results:
Indicators in the logframe
 Percentage of clinical research centres & key staff meet necessary qualification
standards (including reaching internationally recognised standards of practice for
clinical trials (GPP, GCP & GCLP*)). Milestone is that 85% of key clinical research
centre and other staff meet necessary qualification standards to conduct clinical trials
by December 2014.
 Number of active epidemiology studies to support IAVI's research aims. Milestone is 3
more epidemiology studies initiated (bringing total to 10) by December 2016.
 Number of active clinical research studies to support IAVI's clinical research capacity.
Milestone is 1 clinical research study initiated by December 2015.
During the reporting period (2013) IAVI and partners trained over 100 people in the IAVI
Clinical Research Centre network. The training covered Good Participatory Practice (GPP),
Good Clinical Practice (GCP) and Good Clinical Laboratory Practice (GCLP)*. This brings the
total number of people trained in Good Practices to over 1600 in the network since 2002, and
meets the milestone of 85% of all staff trained.
IAVI has supported and is currently conducting seven basic observational epidemiology
studies at its collaborating clinical research centres (CRCs) in 5 African countries, and is well
on track to meet its milestone of 10 studies by December 2016. For example, during the
reporting period, IAVI met individual milestones for a series of studies designed to
characterise the HIV epidemiology in key populations, surrounding the IAVI-supported clinical
network – and has also expanded its evaluation of high-risk cohorts by initiating 2 additional
studies in female sex workers and single mothers in Uganda, Zambia and Rwanda. In
addition IAVI is developing a centre of excellence in Kenya. These studies are important to
guide applied research efforts and trial design. Developing country scientist partners lead
these research studies, enabled by high quality infrastructure, built or strengthened by IAVI. In
addition to the research results themselves, the studies have ‘collateral benefits’ including
informing country’s own public health planning and delivery e.g. Couples Voluntary
Counselling and Testing is now a standard of care for married couples in Rwanda and Zambia
and is being implemented elsewhere, and the Kenyan government increasingly recognises the
need to reach out with prevention and treatment to men who have sex with men. A focus in
2013 was to expand work with vulnerable populations to understand the epidemic, provide
new clues to vaccine design, and to hone Good Participatory Practice (GPP) techniques to
effectively engage and retain relevant key populations to prepare for Phase IIb efficacy trials.
A strong part of IAVI’s work is that they continue to work closely with the local communities
surrounding the clinical research sites, vulnerable groups and civil society organisations, to
ensure understanding and support for AIDS vaccine clinical research. This involves the
provision of regular community information sessions and updates throughout the year,
including a specific focus on religious leaders and civil society groups.
IAVI also supported regular meetings of Community Advisory Boards (CABs) as well as crossCAB consultations in Uganda and South Africa. These interactions are essential for ensuring a
well-informed and engaged board to provide input into the research programme and prepare
for larger-scale trials, and to share best practices and comprehensive updates on the field of
HIV prevention research.
Recommendations:
 IAVI should share the lessons learned working in communities, with other research
groups.
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One of IAVI’s great strengths is the work with researchers in Africa and Asia and the
organisation should ensure that the clinical research centres are supported and
maintained as far as possible
Impact Weighting (%): 15%
Revised since last Annual Review? No
Risk: Medium
Revised since last Annual Review? No
Section B: Results and Value for Money.
1. Progress and results
1.1 Has the logframe been updated since last review? No
1.2 Overall Output Score and Description: A – Outputs met expectation
1.3 Direct feedback from beneficiaries:
DFID has had no direct contact with the beneficiaries of IAVI's work during the reporting
period.
IAVI works in partnership with those hardest hit by the HIV pandemic in low income countries.
They have worked with political leaders, developing country researchers, civil society
organisations, communities etc.
IAVI work with a range of stakeholders and beneficiaries in different countries, to ensure that
HIV prevention research (including vaccines) remains high on the agenda. For example at a
number of high-level African events (e.g. BRICS Minister of Health Conference, East African
Health and Scientific Conference (EAHSC), African Union Summit, Abuja +12).
IAVI’s strategic plan emphasises the continued importance of partnership working and
collaboration with others. In 2012, IAVI surveyed 103 partners, including R&D and advocacy
partners and donors. There was a 51% response rate and overall, 42% of respondents rated
IAVI as an “excellent” partner. In response to these findings, IAVI integrated “partner of
choice” indicators in the 2012 performance process and disseminated revised Organisational
Values to all staff.
1.4 Summary of overall progress
During the reporting period IAVI completed an organisational restructuring intended to
strengthen business practices and enable a greater focus on fewer priorities. IAVI has started
the process of carrying forward a portfolio of technically distinct vaccine candidates and
support efforts of the HIV vaccine field. Work included:
 Launch of Phase 1 trial in Rwanda, Kenya and UK to test first candidate from IAVI’s
replicating viral vector programme
 Advanced the first candidate from IAVI’s broadly neutralising antibody (bnAb)
programme to early development
 Planned the first ‘experimental’ clinical research trial for accelerating design of a bnAbinducing vaccine
 Contributed to the start-up of the HIV Vaccine Translational Research Laboratory in
India, in collaboration with the Indian Government and extension of the India-South
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Africa collaboration, and facilitated the initiation of a new bilateral partnership between
HIV vaccine researchers from India and Australia
1.5 Key challenges
The key challenges that the science of developing an effective HIV vaccine is highly complex,
and although significant progress has been made recently there is still a long way to go and it
remains very high risk.
The longer-term effects of the global financial crisis and a reducing trend in funding HIV
continue to present IAVI with significant funding and sustainability challenges. IAVI have
completed an organisational restructuring and are implementing a 5 year Strategic Plan to
accommodate these changes.
1.6 Annual Outcome Assessment A- outcome met expectations
The development of an effective HIV vaccine is a very long-term process, but many experts
agree that the HIV epidemic cannot be ended without a vaccine. The work is very high risk,
but with a potentially very high return if successful.
IAVI’s work is providing novel approaches to the development of a safe and effective HIV
vaccine. IAVI partners with many research groups working in the field and is able to provide
expertise that is in short-supply, to a range of different research groups in many different
countries.
2. Costs and timescale
2.1 Is the project on-track against financial forecasts: Yes
2.2 Key cost drivers
Vaccine development is a high risk, long term and costly process, particularly during the
clinical trials phase. The PDP model explicitly aims to manage resources to ensure that there
are funds available to test the most promising products as they are developed. This includes
widening partnership with the private sector in low, middle and high income countries and
leveraging of resources, in-kind contributions and expertise; working with other not-for-profit
organisations to share costs wherever possible. But it is worth noting that vaccine
development is more resource intensive than research and development activities in other
areas such as diagnostics and drug development.
2.3 Is the project on-track against original timescale: Yes
3. Evidence and Evaluation
3.1 Assess any changes in evidence and implications for the project
In April 2013 an HIV vaccine trial (HVTN 505) was halted unexpectedly. The sponsoring
agency, the U.S. National Institute of Allergy and Infectious Diseases (NIAID), announced that
a combined regimen of a multi-clade DNA vaccine with an adenovirus-vectored component
(Ad5) was being stopped because an interim analysis, by the independent Data Safety and
Monitoring Board (DSMB), showed that the regimen was not likely to prevent HIV or control
HIV infection.
The DSMB analysis also showed a higher number of HIV infections among the vaccinated
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volunteers compared to placebo recipients, although the results were not statistically
significant. Data from an earlier trial (NIH/Merck Step and Phambili trials, ended in 2007) that
also tested an Ad5 vector had shown increased risk of HIV infection among a subgroup of the
study population and these findings remain unresolved. Combined with data from this earlier
trial, and exercising utmost caution, the NIAID and study team have planned a closer follow-up
of the vaccine recipients over a 5 year follow-up period to ensure the health and safety of the
volunteers. After the trial halt, NIAID notified study participants that vaccinations had stopped
and why.
Following the termination of the HVTN 505 trial, IAVI paused the Sendai + Ad35 trial in
Rwanda. They have revised informed consent to include information about the HVTN 505
findings and secured ethics committee re-approval to continue with the trial.
3.2 Where an evaluation is planned what progress has been made?
None at this time.
4. Risk
4.1 Output Risk Rating: High
4.2 Assessment of the risk level
Product development is long term and high risk and potential new vaccines can fail at any
stage in the development process. The PDP model represents a mechanism to mitigate the
risks associated with the development of vaccines for diseases where there is little likelihood
of private sector companies recovering the costs of development due to perceived risks and
profit potential. IAVI manages these risks on an ongoing basis, through monitoring its portfolio
and prioritising or stopping research as appropriate when data indicates a change in the
probability of success of a vaccine candidate.
Significantly reduced funding levels have threatened the sustainability of the organisation in
recent years, and IAVI have responded to the challenges over the last few years, they have
improved business practices and organisational efficiency and made the organisation leaner;
and they are looking to develop more collaborative partnerships to further mitigate risks and
improve efficiency across the HIV vaccine community. In the longer term, the approach
outlined in their new Strategic Plan should continue to mitigate financial risks whilst making
IAVI, and HIV vaccine research, more efficient.
Under the guidance of the Senior Director of Regulatory Affairs and Quality Assurance, a
Global Quality Assurance Unit (GQAU) comprised of Regulatory Affairs, Quality Systems, and
Laboratory Quality Assurance, oversees and performs a range of quality and risk
management- related activities, in conjunction with various R&D functional units and external
consultants. Such activities include, but are not limited to, the establishment of annual quality
work plans, periodic audits and reviews of relevant policies, procedures and activities of key
sub-recipients and partners.
4.3 Risk of funds not being used as intended
This is a low risk.
IAVI’s Finance & Administration department, under the leadership of the Chief Financial
Officer (CFO) provides a comprehensive system of internal controls, financial management
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and compliance to ensure accountability and sound stewardship of donor resources.
An independent Financial audit of IAVI’s financial position is undertaken annually. Copies of
unqualified Audited Financial Statements for 2013 have been examined by DFID.
The provision of core funds to manage its portfolio of potential vaccines is a way to manage
the risk that any one project is unsuccessful and that work will stop. The organisation is able to
reassign funds to more promising projects and ensure that work continues.
In 2013, IAVI conducted 3 substantive and 13 compliance audits, based on the 2013 risk
assessment performed at the beginning of the year. During these audits there was a finding
considered material at on partner organisation, which related to unreconciled receivables and
payables. The IAVI staff are following up on this finding to resolve the issue. There were no
whistleblower reports.
4.4 Climate and Environment Risk
There are no significant environmental impacts of IAVI’s work at this time. As with other PDPs,
in the longer term the environmental impacts of IAVI’s activities should be positive with
improved treatments / prevention of disease in poor populations contributing to more effective
and efficient use of drugs and associated health services.
5. Value for Money
5.1 Performance on VfM measures
Funding vaccine development through a PDP such as IAVI provides value for money through:
 The use of a portfolio approach which allows funding to be redistributed if individual
projects are stopped if they do not meet their milestones.
 Support for the continued development of the most promising candidates: facilitating
opportunities to explore innovative partnerships with private and public sector
organisations (in many different countries including low and middle income) to reduce
costs.
 Specify target product profiles for new vaccines to be developed at the lowest possible
unit cost.
 Adopting measures to speed up the R&D process, such as early access to research
data to shorten timelines for vaccine development, the Vaccine Product Development
Centre to build on successes of pilot stage programmes and to move candidates
forward through the development process to clinical testing.
 Leveraging contributions from the private sector and/or in-country funds, by fostering
country ownership and encouraging emerging economies to invest in AIDS vaccine
development. Work is ongoing in India and partnerships are developing between
research groups in India, South Africa and Australia.
 Developing partnerships with other entities to support joint activities (e.g. clinical trial
site development, development of assays). For example, the development of framework
agreements with the HIV Vaccine Trial Network to access clinical trial sites and clinical
research centres. IAVI has assisted the development of links between different
research networks, to share resources and access to sophisticated equipment, which
would otherwise be very costly to set up and run.
IAVI further enhances its value for money through strong partnership working with policy
makers, influencers, other researchers, civil society and communities. Such involvement
significantly increases the likelihood and timeliness of vaccine uptake in endemic countries.
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5.2 Commercial Improvement and Value for Money
IAVI has taken a strategic approach to strengthening value for money over the last year, and
has made some significant changes, including: restructuring the organisation and reducing
staff numbers; and moving into scientific areas most needed to achieve its mission (e.g.
change in focus on immunogen design and advancement within the Neutralising Antibody
Consortium, and the focus on establishing phase 2b trials).
IAVI has revised policies to improve the efficiency of use of funds (e.g. improvements in
procurement, human resource and portfolio management). As a result of the ongoing cross
organisational business processes review, IAVI has instituted quarterly Project Integration
Meetings to track and align budgeting, donor reporting, and programme planning and
implementation functions. Core elements of the portfolio management system across R&D
have been strengthened and there have been improvements to the grants management
process, with specific workflows and reporting structures, to maximise cost recovery
IAVI’s internal R&D processes help to secure value for money, by identifying the most
promising candidates, from different groups, to take forward and robustly manage the portfolio
to ensure that go/no go decisions are taken appropriately and timely manner.
5.3 Role of project partners
DFID is one of a number of donors all of whom are involved through regular discussions with
the programme directly and through various international and WHO based fora. All donors are
aware of the financial constraints and the need to identify ways to increase value for money.
Ensuring value for money in developing products for use in low income countries, where there
is no viable commercial market, is central to the way PDPs work with their partners from a
range of different backgrounds, including private sector organisations, academic researchers,
advocacy organisations and local community groups.
There have been some changes to the Board of Directors and three new members
(Ambassador Eric Goosby, Rt Hon the Lord Fowler and Professor Robin Weiss), became
directors in 2013.
5.4 Does the project still represent Value for Money : Yes
5.5 If not, what action will you take?
6. Conditionality
6.1 Update on specific conditions
Not applicable
7. Conclusions and actions
IAVI’s work is progressing well and the organisation is on track to reach its milestones and
targets over the next five years, taking into account the high risk nature of this research.
There have been some advances, and disappointments, in the science for HIV vaccine
research in recent years. Without an HIV vaccine it will be very difficult to end the epidemic
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and the work of IAVI is important in ensuring that vaccine research has a focus on the needs
of low income countries. IAVI and partners are exploiting new scientific tools to speed up
vaccine development, including the use of synthetic biology and innovative clinical trial design.
Recommendations:
 IAVI should share the lessons learned working in communities, with other research
groups.
 The organisation should ensure that the clinical research centres are supported and
maintained as far as possible
8. Review Process
The review was carried out by members of the Human Development Team in DFID’s
Research and Evidence Division following active participation in Amsterdam in February 2014
at the donor roundtable consultation meeting and a follow up, discussion with IAVI’s Chief
Executive Officer and other staff members. During the donor meeting the range of challenges
facing IAVI (both technical and business related) were fully and openly discussed. The review
has taken into account the views of IAVI’s donors present at the meeting in February 2014.
Account was also taken of further supporting materials including reports from the IAVI website,
annual reports and regular e-mail updates.
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