Investing to End the AIDS Epidemic: A New Era for HIV Prevention Research & Development
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Investing to End
the AIDS Epidemic:
A New Era for HIV Prevention
Research & Development
J u ly 2 0 1 2
HIV Vaccines and Microbicides Resource Tracking Working Group
www.hivresourcetracking.org
AVAC Global Advocacy for HIV Prevention
IAVI International AIDS Vaccine Initiative
IPM International Partnership for Microbicides
UNAIDS Joint United Nations Programme on HIV/AIDSwww.hivresourcetracking.org Investing to End the AIDS Epidemic: A New Era for HIV Research & Development 1
Content
›
3 1.0 Introduction
4 1.1 Executive Summary
9 2.0 HIV Prevention R&D
9 2.1 Global Investments in HIV Vaccine R&D
11 2.1.1 Public Investments in HIV Vaccine R&D
14 2.1.2 Philanthropic Investments in HIV Vaccine R&D
14 2.1.3 Commercial Investments in HIV Vaccine R&D
17 2.1.4 Funding Allocations for HIV Vaccine R&D
17 2.1.5 Global Investments in Therapeutic HIV Vaccine R&D
18 2.2 Global Investments in Cure Research
19 2.3 Global Investments in Microbicide R&D
21 2.3.1 Public Investments in Microbicide R&D
22 2.3.2 Philanthropic Investments in Microbicide R&D
22 2.3.3 Commercial Investments and Contributions to Microbicide R&D
23 2.3.4 Funding Allocations for Microbicide R&D
23 2.3.5 Investments in Rectal Microbicide R&D
24 2.4 Global Investments in R&D and Operations Research for
Other HIV Prevention Options
24 2.4.1 Investments in Follow-Up Studies and Operations Research
Related to Adult Male Circumcision
24 2.4.2 Investments in R&D Related to Pre-Exposure Prophylaxis
26 2.4.3 Investment in R&D Related to Treatment as Prevention
26 2.4.4 Investments in HIV Prevention R&D Related to HSV-2 Prevention
27 2.4.5 Investments in Operations Research Related to
Vertical Transmission Prevention
27 2.4.6 Investments in R&D and Operations Research Related
to Female Condoms
28 2.5 Investments by Trial Participants
29 3.0 Discussion
32 Appendix: Methodology
34 Appendix: List of Acronyms
35 Appendix: Acknowledgements
37 Appendix: Endnotes2 Investing to End the AIDS Epidemic: A New Era for HIV Research & Development www.hivresourcetracking.org
List of Tables
4 Table 1 HIV Prevention R&D Investments Over Time
6 Table 2 Investment Snapshot for 2011
10 Table 3 Annual Investments in HIV Vaccine R&D from 2006–2011
12 Table 4 Top HIV Vaccine Funders for 2010 and 2011
14 Table 5 Philanthropic Investment in HIV Vaccine R&D by Foundations and
Commercial Philanthropy in 2011
15 Table 6 Estimated Commercial Engagement in HIV Vaccine R&D by Company in 2011
19 Table 7 Annual Investments in Microbicide R&D from 2006–2011
20 Table 8 Top Microbicide Funders for 2010 and 2011
25 Table 9 Annual Investments in Pre-Exposure Prophylaxis from 2005–2011
27 Table 10 Funding for Vertical Transmission Prevention R&D from 2008–2011
32 Table 11 Categories Used to Classify Preventive HIV Vaccine R&D Funding
33 Table 12 Categories Used to Classify Microbicide R&D Funding
List of Figures
5 Figure 1 Global HIV Prevention R&D Investments from 2005–2011
8 Figure 2 Investing in HIV Prevention R&D to End the Epidemic:
2011 Investments and Progress
9 Figure 3 HIV Vaccine Funding from 2000–2011
11 Figure 4 Total Global Investment in HIV Vaccine R&D Breakdown 1997 vs. 2011
12 Figure 5 Total Global and NIH Investment in HIV Vaccine R&D 1997 vs. 2011
13 Figure 6 Public Sector Donors Who Increased Funding for HIV Vaccine R&D in 2011
16 Figure 7 HIV Vaccine Expenditures from 2001–2011
17 Figure 8 Investment in Therapeutic HIV Vaccines 2010 and 2011
18 Figure 9 Investment in Cure Research 2010 and 2011
20 Figure 10 Microbicide Funding from 2000–2011
21 Figure 11 Microbicide Funding from 2000–2011
23 Figure 12 Microbicide Expenditures from 2006–2011
25 Figure 13 Investment in Pre-Exposure Prophylaxis from 2005–2011
28 Figure 14 Funding for Female Condom R&D in 2010 and 2011
List of Text Boxes
15 Box 1 HIVACAT Collaboration in Action
16 Box 2 Local Production
24 Box 3 Patient Capital
31 Box 4 Conclusionswww.hivresourcetracking.org Investing to End the AIDS Epidemic: A New Era for HIV Research & Development 3
Introduction 1.0
In June 2011, thirty years after the start of the AIDS epidemic, heads of state and other
high-level government officials gathered in New York for the United Nations General Assembly
High-Level Meeting on AIDS. At that landmark meeting, UNAIDS Executive Director
Michel Sidibé called on leaders to end the epidemic by agreeing on a common agenda—an
agenda that would allow us to achieve the goal of “zero new HIV infections, zero discrimination
and zero AIDS-related deaths.”
At the 2011 High-Level Meeting, UN member that HIV prevention and treatment could end
states were also called on to reaffirm their the AIDS epidemic.3
commitment to the Declaration of Commitment
Yet, just as 2011 was yielding significant new
on HIV/AIDS, adopted by member states in 2001,
and to make new commitments, both financially and HIV/AIDS prevention opportunities, the realities
through action, to sustain the global AIDS response. of the global economic climate created constraints
for global health financing in general. A scarcity
The 2001 Declaration had specified a set of global of funding led to increased pressure to provide
and national indicators to be monitored annually, evidence of impact and to deliver immediate value
the second of which was the “amount of public for money invested. Despite scientific successes,
funds available for research and development some development agencies have pulled back
(R&D) of vaccines and microbicides.”1 The from funding long-term research. Additionally,
HIV Vaccine & Microbicides Resource Tracking emphasis has shifted away from single-disease-
Working Group (the “Working Group”) took
specific projects to other priorities, such as health
on that task and has for 10 years collected and
systems strengthening4 and broader efforts to
analyzed public, philanthropic and other private-
address non-communicable diseases.
sector funding for HIV vaccine and microbicide
R&D. As research evolved, the Working Group To navigate the tensions between increased
extended its monitoring reach to include R&D fiscal austerity, competing priorities and the
investments in other HIV prevention options. The enduring need to sustain and advance research,
Working Group acts as collectors and analysts of HIV prevention R&D has had to adapt. The
funding information for use by Working Group global HIV prevention research field has sought
members and other advocates and partners, and to become more efficient, results-driven and
not as policy-makers or spokespeople for the HIV coordinated. Efficiencies in the conduct of clinical
prevention research field. trials and collaborations by product development
Since publication of the first Working Group partnerships (PDPs) and other product developers
report,2 HIV prevention research has progressed, are allowing for greater progress with fewer
and its priorities have moved beyond biomedical resources.5 Implementation initiatives blending
research to embrace implementation research and prevention and treatment are underway, as are
combination prevention. In the past year, a flood joint explorations by researchers and implementers
of research results showing proof of concept, or to integrate HIV prevention R&D and research
effectiveness, of new prevention options has both on tuberculosis, malaria, other neglected diseases
expanded the research agenda and moved public and family planning—addressing improving
discourse to an evidence-based understanding overall health.4 Investing to End the AIDS Epidemic: A New Era for HIV Research & Development www.hivresourcetracking.org
1.1 Executive Summary Global investment in microbicide R&D has
reached nearly US$2 billion over the past 10
years, with an average yearly investment of
Global Investments US$196 million—US$10 million more than
Since 2001, global preventive HIV vaccine R&D the investment of US$186 million in 2011. The
investment has totaled US$8 billion, with an public sector provided the majority of the funding
average yearly investment of US$824 million. The in 2011, at US$176 million (95 percent). The
2011 investment was US$845 million, US$14 philanthropic sector provided US$9 million (5
million lower than in 2010. The public sector percent), and the commercial sector contributed a
provided the majority of funding in 2011, at little over US$1 million (www.hivresourcetracking.org Investing to End the AIDS Epidemic: A New Era for HIV Research & Development 5
Global investments in other Figure 1 Global HIV Prevention R&D Investments from 2005–2011 (US$ millions)
prevention technologies totaled
US$203 million in 2011. Treatment as Prevention*
Investments directed toward Adult Male Circumcision
Pre-exposure Prophylaxis
male circumcision, reducing
Microbicides
vertical transmission at birth and Preventive Vaccines
$1,200
during breastfeeding, treatment
as prevention, pre-exposure
prophylaxis (PrEP), and female $1,000
condom R&D increased overall
from 2010 by US$41 million
(25 percent). In 2011, public- $800
sector sources provided US$152 US Dollars (millions)
million (75 percent) and the
philanthropic sector provided $600
US$51 million (25 percent). The
commercial sector provided in-
kind assistance in the form of $400
antiretroviral (ARV) drugs and
assays to be tested and used in
$200
preclinical and clinical research,
and in R&D directed at the
next-generation female condom. 0
2005 2006 2007 2008 2009 2010 2011
Scientific Advances * The Working Group began tracking funding for treatment as prevention in 2010.
While total funding for all HIV
prevention R&D decreased by US$30 million Italy, in July of 2011 showed the effectiveness
from 2010 to 2011,7 HIV prevention science of taking daily oral ARV drugs to reduce HIV
had one of its most successful years in 2011.8 acquisition among HIV-negative individuals in
The world is further than ever before along heterosexual serodiscordant couples. The TDF210
the scientific pathway to the end of the AIDS and Partners PrEP11 studies built on the iPrEx
epidemic. In 2011, as in 2010, advances were made study results released in 201012 by showing that
both across the full spectrum of R&D for HIV PrEP reduces HIV transmission in heterosexuals
prevention options and in the translation of R&D as well as gay men and men who have sex with
into on-the-ground realities. men (MSM). Based on these findings, the
US Food and Drug Administration (FDA) is
The first of these advances came in May 2011, with reviewing Gilead Science’s application for an
the results from the HPTN 052 study, honored by indication for tenofovir/emtricitabine (TDF/
Science magazine as the “Breakthrough of the Year”. FTC) as PrEP for all adults and has set a deadline
The study showed that initiating antiretroviral of September 2012 for its decision.
therapy (ART) in HIV-positive people at an early
stage and maintaining adherence to that treatment Additional follow-up analysis of the RV144
regimen reduced the risk of transmission of HIV Thai vaccine trial revealed another significant
to an HIV-negative partner by 96 percent. HPTN discovery in September at the AIDS Vaccine
052 became the first randomized clinical trial to 2011 Conference in Bangkok, Thailand.13 Aiming
show what many had long suspected: treatment is to better understand how RV144 protects
also prevention.9 against HIV infection, the study team found
two important molecular clues—two antibodies
The results of two studies released at the correlated with the risk of HIV infections. This
International AIDS Society conference in Rome, highly-anticipated post hoc analysis, along with an6 Investing to End the AIDS Epidemic: A New Era for HIV Research & Development www.hivresourcetracking.org
Table 2 Investment Snapshot for 2011
HIV Prevention Amount Amount Change
Option 2011 2010 from 2010 Headlines
The year saw lower US public-sector investment and
Preventive US$ 845 US$ 859 -US$14
the end of the US stimulus package, along with lower
vaccines mn mn mn (-2 %)
European investment overall.
The year was one of preparation for clinical trials and
US$ 186 US$ 247 -US$61 decreased investment, due in part to the cyclical nature of
Microbicides
mn mn mn (-25 %) clinical trials, with many follow-on and large-scale trials
set to begin in 2012 and beyond.
PrEP funding in 2011 saw increased funding as a result
Pre-Exposure US$ 62.3 US$ 58.3 +US$4 of the large-scale trials that took place in 2011, with next-
Prophylaxis mn mn mn (+7 %) generation and follow-on trials getting ready to begin in
the following years.
While funding for R&D and operations research may have
Adult Male US$ 20.3 US$ 21.7 -US$1.4 decreased slightly in 2011, this is due to an increase
Circumcision mn mn mn (-6 %) in implementation, rollout and scale-up of adult male
circumcision as a proven HIV prevention technology.
Funding increased substantially due to improved data
Treatment as US$ 79.4 US$ 19.6 +US$59.8
collection and a post–HPTN 052 focus on scale-up of
Prevention mn mn mn (+305 %)
treatment as prevention trials worldwide.
Budget constraints and competing priorities led to an
All HIV $US 1.24 $US 1.27 $US 30
overall flatlining of global HIV prevention R&D spending
prevention R&D bn bn mn (-2%)
in 2011.
array of new insights into the mechanics of broadly Key Conclusions
neutralizing antibodies against HIV brought the
In line with global health research and
vaccine field closer than ever before to finding a
development trends overall,14 this year’s resource
strategy for an effective HIV vaccine.
tracking analysis found that funding had decreased
In October, the FACTS 001 trial started, testing slightly–an effective flatlining of investment in
the safety and effectiveness of 1% tenofovir gel in HIV prevention R&D. Yet, in an age of economic
preventing HIV and herpes simplex virus type 2 challenges, continued investment without
(HSV-2) in women. The results of FACTS 001 significant cuts can be considered a sign that
will enable the field to understand the effectiveness the top funders understand the importance of
of 1% tenofovir gel, particularly important in light continuing to invest in HIV prevention R&D.
of the discontinuation of the 1% tenofovir arm of Overall, investments in vaccine and microbicide
the VOICE trial in November. R&D decreased. Yet, the decreases for microbicide
Public- and private-sector funders sustained R&D can be attributed to funding disbursement
investments in HIV prevention research in 2011. cycles and do not represent declines as compared
Yet, the need for long-term support to ensure with past investments. Funders increased their
success in these endeavors was confronted by investments for PrEP and treatment as prevention
escalating budget constraints in an increasingly research, supporting clinical trials that in turn have
volatile global economy and shifts in research yielded groundbreaking results.
focus. These challenges underscore the need for a
strategic revitalization of public- and private-sector In 2011, the field began to see the effects of a
investments–one that is essential to completing challenging global economic environment, with
ongoing trials efficiently, supporting confirmatory reductions in public-sector funding in many donor
trials and transforming recent discoveries into new, countries. While some public-sector donors reduced
diverse and more effective HIV prevention options. their funding levels in 2011, the Bill & Melindawww.hivresourcetracking.org Investing to End the AIDS Epidemic: A New Era for HIV Research & Development 7
Gates Foundation (BMGF) and a number of other microbicide research for 2012. In 2011, the
philanthropic donors filled some of the funding International AIDS Vaccine Initiative (IAVI) and
gap, increasing their investments for vaccines and the Translational Health Sciences and Technology
other prevention options by nearly US$20 million. Institute (THSTI), an institute of the Indian
Across both the public and philanthropic sectors in government’s Department of Biotechnology,
2011, shifting investment strategies led new funders launched a program, known as the HIV Vaccine
to invest in HIV prevention R&D and long-time Design Program. In 2012 the program will open
donors to adjust their funding. a new center on the campus of THSTI in New
Delhi. South Africa has hosted numerous clinical
With advances in research come the expenses
trials of different prevention technologies, and
associated with the later stages of R&D. It is critical
Thailand is hosting vaccine and PrEP trials. Local
that donors continue to explore ways in which HIV
production is also on the rise. For example, in 2011,
prevention trials can be funded in order to plan
CONRAD and the South African government’s
for and complete the large-scale, late-stage trials
Technology Innovation Agency (TIA) signed
needed to apply for regulatory approval. In the short
a license agreement that grants TIA the right
term, funding will need to meet the requirements of
to manufacture and distribute tenofovir 1% gel
research institutions and entities preparing to launch
in Africa as soon as it has confirmatory results
these studies in 2012 and beyond.
and regulatory approval. The expansion of the
funding base with new contributors is making a
The Structure of Funding critical difference in advancing research—which is
especially important as traditional funders decrease
Funder concentration. Funding for HIV prevention
their investments.
remains highly concentrated among relatively few
funders. Although nearly all public-sector donors Philanthropic funding was relatively concentrated
decreased their funding in 2011, decreases in US among a few top funders. Some philanthropies
and European investment have been the most decreased their funding in 2011; however, new
profoundly felt. Research agencies are fighting funders entered the HIV prevention R&D field,
for funding, as budgets are cut and fewer grants making substantial contributions to a variety of
disbursed. Development agencies are, in some cases, R&D efforts.
increasingly focused on implementation of global
Emerging efficiencies. As the field of HIV
health technologies that have quick, measurable
prevention evolves, so do the organizations
outcomes rather than on long-term R&D projects
and research institutions undertaking R&D
for which the results are uncertain.
projects. Members of the HIV prevention
Thus, the sustained and increased investments field have increasingly come together to form
by some lower- and upper-middle-income partnerships and joint endeavors in order to
countries—including India, China, South Africa become more efficient and streamlined in
and Thailand—as well as their participation in conducting R&D. Partnerships and collaborations
R&D projects, are now proving critical both to are vital to the success of the field, and they
broadening the prevention research funding base require the participation of the public, private
and to expanding research globally. China has and philanthropic sectors. Further efficiencies
continued to invest in HIV prevention research. can be achieved as researchers across prevention
While China is currently between funding cycles approaches share and develop crosscutting research.
for its HIV vaccine R&D program, investments
Funding allocations. It has been challenging to
from the country continue to prove invaluable
obtain data on funding allocations for categories
to moving R&D forward across a variety of
of R&D expenditure (e.g., basic research, clinical
prevention options. India’s Department of
trials, etc.).15 Yet, reporting shows that the majority
Biotechnology (DBT) and the Indian Council
of funding for both microbicides and vaccines over
of Medical Research (ICMR) collaborative
the past five years has been allocated to preclinical
program on “HIV/AIDS and Microbicides”
research and clinical trials.
is soliciting proposals for HIV vaccine and8 Investing to End the AIDS Epidemic: A New Era for HIV Research & Development www.hivresourcetracking.org
Figure 2 Investing in HIV Prevention R&D to End the Epidemic: 2011 Investments and Progress
The field is closer than ever before to an effective
Developing new
DEVELOP
HIV vaccine with the discovery from RV144
HIV prevention Vaccines researchers of two antibodies whose presence
options through either increases or decreases the risk of HIV.
research and US$ 845 million The only large scale efficacy trial, HVTN 505, is
development scheduled to release results in 2013, moving the
field even closer to the reality of a vaccine.
The results of CAPRISA 004 are being built upon
by trials underway. New technologies – a ring,
Microbicides
DEMONSTRATE
long-acting injectable and rectal formulation – are
Demonstrating being tested. A marketable product is within reach
new HIV US$ 186 million and the field has moved to form partnerships and
Prevention collaborations furthering its efficiencies.
options in
implementation PrEP has been proven effective for heterosexual
studies Pre-Exposure Prophylaxis couples and men who have sex with men. It is
at the beginning of the roll-out stage as the FDA
US$ 62.3 million reviews Gilead’s application for Truvada as PrEP
for adults.
Treatment as Prevention HPTN 052 proved that treatment as prevention
works. Roll out of treatment as prevention is
DELIVER
Delivering
proven HIV US$ 79.4 million occurring worldwide.
prevention
tools Male circumcision Rollout of voluntary adult male circumcision
is on the rise.
US$ 20.3 million
Combined, these new options could get the field
Total of US$ 1.24 billion closer to ending the epidemic. Investing in these
tools is crucial to avert new infections.
Aside from vaccines and microbicide R&D three percent of all funding for microbicide R&D
expenditures, the Working Group is not able to was allocated to behavioral and social science
track allocations of R&D funding for prevention research. Increased investment in behavioral and
options. The lack of information on allocations for social science research is in accord with the view
other prevention options is a critical gap in resource expressed in recent international and US domestic
tracking as the fundamental issue of uptake and guidance documents16 on the necessity of social
adherence across all new options is paramount to science research within and beyond the context
the success of any new tool. As products advance of clinical trials.17 As clinical data shows the
through clinical trials and the reality of new, importance of adherence to regimens, additional
marketable prevention options is imminent, it is social science research is increasingly vital to the
imperative that investment in behavioral and social success of new technologies.
science research becomes a priority. In 2011, onlywww.hivresourcetracking.org Investing to End the AIDS Epidemic: A New Era for HIV Research & Development 9
2.0 HIV Prevention R&D
2.1 G lobal Investments in HIV Vaccine R&D
Since 2001, global preventive HIV vaccine R&D investment has totaled US$8 billion, with an
average yearly investment of US$824 million. The 2011 total investment was US$845 million,
a decrease of US$14 million from 2010. As in past years, public-sector funders provided the largest
part of the investment, followed by the philanthropic sector and the commercial sector.18 In 2011,
the public sector provided US$702 million (83 percent), the philanthropic sector provided US$113
million (13 percent) and the commercial sector contributed US$30 million (4 percent). Investment
by European governments was US$48.5 million, a decrease of over US$12 million (21 percent)
from 2010, and a 40 percent decrease from the US$82 million peak in 2006. Philanthropic
investments in HIV vaccine R&D increased in 2011 by US$10 million (10 percent).
In 2011, RV144 researchers revealed new findings, are supported primarily through public-sector
identifying two correlates of immunity that funding and are collaborative efforts among a
have the potential to move the field closer to an range of public and private-sector entities.
effective vaccine. In addition, over 30 other HIV RV144 researchers presented results at the AIDS
vaccine trials were underway. Most ongoing trials Vaccine 2011 conference in Bangkok, Thailand,
Figure 3 HIV Vaccine Funding from 2000 - 2011 (US$ millions)
$1000 Commercial
961
Europe 933
Multilaterals
$900 868 868 859
Other 845
Philanthropic
$800
US 759
$700 614
US Dollars (millions)
$600
548 547
$500
$400 366
327
$300
$200
$100
0
2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 201110 Investing to End the AIDS Epidemic: A New Era for HIV Research & Development www.hivresourcetracking.org
of a two-year effort to identify an immunological HIV vaccine field. The Vaccine Research Center
explanation for the modest 31 percent efficacy (VRC) of the National Institute of Allergy and
afforded by the prime-boost vaccine regimen Infectious Diseases (NIAID) has been focused
tested in the RV144 trial. Two immune responses on designing vaccines to stimulate broadly
were found to correlate significantly with HIV neutralizing antibodies against HIV. The VRC
infection rates in RV144 vaccine recipients: The has completed novel research using computational
first, involving immunoglobulin IgG antibodies biology to design immunogens capable of eliciting
that bind to the V1/V2 variable loops in the HIV antibodies in animal models.
envelope, correlated with a 43 percent reduction in
HIV infection rate. The second involved plasma Additionally, in 2009, IAVI established the
IgA antibodies that bind to the HIV envelope and Neutralizing Antibody Center at the Scripps
correlated with a 54 percent increase in the HIV Research Institute dedicated to studying
infection rate. Follow-up trials are now underway. neutralizing antibodies. The Center is the hub for
RV305, a small immunogenicity study that aims IAVI’s Neutralizing Antibody Consortium, which
to evaluate extended boosting regimens using the has isolated more than two-dozen antibodies
same vaccine components as RV144, began in from volunteers worldwide, deciphered some of
Thailand in April 2012. RV305 is the first of two the structures of the most potent antibodies and
planned follow-up trials to RV144, with the second applied their discoveries to the design of novel
study, RV306, expected to begin later in 2012. vaccine candidates.
Additional studies evaluating a prime-boost Larger pharmaceutical companies are entering
mechanism similar to that used in RV144 are into antibody research and several biotechnology
being planned for initiation in 2013 and 2014 in companies are also engaged in R&D that has
Thailand, Uganda and South Africa. yielded promising results.
Broadly neutralizing antibody research is a large The year 2011 saw more than just the identification
focus of R&D efforts and collaboration within the of new broadly neutralizing antibodies. Additional
Table 3 Annual Investments in HIV Vaccine R&D from 2006 – 2011 (US$ millions)*
2006 2007 2008 2009 2010 2011
PUBLIC SECTOR
US 654 659 620 649 632 623
Europe 82 79 69 65 61 48.5
Other public sector 38 49 41 31 32 30
Multilaterals 2 2 1 1 1 0.5
Total public 776 789 731 746 726 702
PHILANTHROPIC SECTOR
Total philanthropic 78 88 104 92 103 113
NON-COMMERCIAL SECTOR
Total non-commercial 854 877 835 838 829 815
COMMERCIAL SECTOR
Total commercial 79 84 33 30 30 30
Total global investment 933 961 868 868 859 845
* Numbers may be rounded, including total.www.hivresourcetracking.org Investing to End the AIDS Epidemic: A New Era for HIV Research & Development 11
Figure 4 Total Global Investment in HIV Vaccine R&D Breakdown 1997 vs. 2011 (Valued in 2011 US$ millions)
1997 Investment: US$ 261 million 2011 Investment: US$ 845 million
$.5M
$30M
United States $30M
$48.5M $113M
Philanthropic
$79M
Non-US Global
Europe
Industry
$182M $623M
Other Government
Multilaterals
advances have been made in identifying the HIV infection as an end point for analysis.19 HVTN
structures of antibodies, how they evolve and how 505 is expected to release results in early 2013.
they are produced by the immune system. These
discoveries help researchers in identifying new 2.1.1 P ublic investments in
targets, understanding how and where antibodies HIV vaccine R&D
interact with HIV and how they are able to
block the virus from infecting cells. Furthermore, Public-sector funding has accounted for the
VRC was able to map the way in which broadly majority of funding for HIV vaccine research since
neutralizing antibodies evolve. Collectively, these research began. National research agencies, through
discoveries provide clues to design and evaluate investigator-initiated programs, have been successful
vaccine candidates that can elicit such antibodies. in supporting basic, preclinical and clinical research.
Public agencies and institutions accounted for 83
EuroNeut-41, funded under the European Union’s percent of all investments in 2011. Agencies in
(EU) Seventh Framework Programme (FP7), the US alone accounted for 74 percent of HIV
aims to develop new vaccines capable of eliciting vaccine R&D funding. The United Kingdom
neutralizing antibodies. The EuroNeut-41 project (UK) and Canada were the second- and third-
involves 17 partners, including Sanofi Pasteur, largest contributors, investing US$18.0 million and
the University of Granada in Spain, Polymun US$13.0 million, respectively.20 Public agencies in
Scientific, Clinical Research Centre at the eight additional countries invested more than US$1
University of Surrey and PX’Therapeutics. million each. Ten public agencies increased their
Among other trials moving forward is HVTN investment from 2010 to 2011.
505, currently the only active vaccine efficacy trial. The final disbursement of stimulus funding
HVTN 505 is a Phase IIb trial evaluating a DNA from the American Recovery and Reinvestment
prime and adenovector vaccine boost to assess Act (ARRA) came in 2010, providing US$26.7
whether it prevents infection or lowers the viral million in NIH funding for HIV vaccine R&D.
load of individuals who seroconvert during the While there was only a two percent drop in
trial. The regimen is being tested in over 2,000 overall funding for HIV vaccine R&D in 2011,
gay men, MSM and transgender women in the and a three percent drop in US funding, the
US. In 2011, the trial changed its protocol to add current budget debates could influence funding12 Investing to End the AIDS Epidemic: A New Era for HIV Research & Development www.hivresourcetracking.org
Figure 5 Total Global and NIH Investment in HIV Vaccine R&D 1997 vs. 2011 (Valued in 2011 US$ millions)
Global Investment 2011: US$ 845 million NIH Investment 2011: US$ 550 million
Present-Day Value
Comparisons of over a decade
are made in presen day value in
order to best show the increase
in investment, without the
2011 increases caused by inflation.
$845M
2011
$550M
1997
$261M 1997
$182M
for the NIH, the US Agency for International Budget Control Act of 2011, significant cuts on
Development (USAID) and the US Department the order of eight percent are proposed for the
of Defense’s Military HIV Research Program NIH starting in January 2013.
(MHRP) in 2012 and 2013. Pressure on the US
Most members of the G821 and 11 members of
Congress to cut spending grew in 2011 and early
the G2022 supported HIV vaccine research in
2012. Under the sequestration provisions of the
Table 4 Top HIV Vaccine Funders for 2010 and 2011 (US $millions) 23
2010 Rank Funder Amount 2011 Rank Funder Amount
1 NIH 561.6 1 NIH 550.4
2 BMGF 80.9 2 BMGF 78.5
3 MHRP 41.6 3 MHRP 43.3
4 USAID 28.7 4 USAID 28.7
5 EC 19.9 5 DFID 11.8
6 Chinese Government 18.3 6 Ragon Foundation 10.0
7 DFID 16.6 7 EC 10.3
8 Ragon Foundation 10.0 8 ANRS 7.3
9 ANRS 6.6 9 Chinese Government 6.9
10 Wellcome Trust 5.1 10 Wellcome Trust 6.5
11 UK MRC 5.0 11 UK MRC 6.2
12 EDCTP 4.5 12 CHVI 5.8
13 CIDA 3.8 13 CIDA 4.9
14 AECID 3.6 14 NMHRC 3.9
15 NORAD (Norway) 2.5 15 Government of the Netherlands 3.8www.hivresourcetracking.org Investing to End the AIDS Epidemic: A New Era for HIV Research & Development 13
2011, with China, Canada, the EU, France, the decreased by approximately 50 percent to US$10
UK and the US contributing more than US$5 million. This is on par with the larger trend of
million. Support from Canada, France and Japan decreased funding from European countries, with
increased in 2011. Canada significantly increased Italy, the Netherlands, the UK and Spain all
its R&D investment through the Canadian reporting lower funding in 2011.
Institutes of Health Research (CIHR) and is a
Public-sector funding has also been the backbone
top funder of HIV vaccine research. The CIHR
of many large PDP efforts and supports
HIV/AIDS Research Initiative oversees the
collaborations with other sectors, such as the
Federal Initiative to Address HIV/AIDS in
commercial sector. Many commercial-sector
Canada and the Canadian HIV Vaccine Initiative.
efforts are incentivized through grants offered by
These initiatives provide US$22.5 million
the public sector. For instance, the US government
annually to support research.
supports the work of the HIV Vaccine Trials
Funding from the European Commission (EC) in Network (HVTN), testing commercial available
2011 declined dramatically from the previous year. vaccines, through NIAID. The US NIH-
In 2010, the EC invested US$20 million in HIV supported HVTN 505 is the only vaccine efficacy
vaccine R&D. However, in 2011, EC funding trial currently underway that is testing a DNA/
Public Sector Donors Who Increased Funding for HIV Vaccine R&D in 2011
Figure 6
How much did donor funding increase?
US$ 1,710,000
$44M Increase in amount invested in 2011
2010
$43M
$42M
$41M
US Dollars (millions)
$40M
US$ 657,787
$9M
US$ 1,115,704
$8M
US$ 4,946,730
$7M
US$ 1,062,010
$6M
US$ 2,377,320
US$ 1,734,508
$5M
$4M
US$ 977,544
US$ 1,185,585
US$ 90,899
$3M
US$ 75,598
$2M
$1M
$0
ANRS CIDA CHVI CIHR DANIDA Irish Aid Japan MHRP UK MRC SAAVI SIDA14 Investing to End the AIDS Epidemic: A New Era for HIV Research & Development www.hivresourcetracking.org
Philanthropic Investment in HIV Vaccine R&D by Foundations and Commercial Philanthropy
Table 5
in 2011 (US$)
US$ 78.5 million BMGF
US$ 5 million to US$ 10 million Ragon Foundation, Wellcome Trust
US$ 1 million to US $ 5 million OFID, Starr Foundation
Doris Duke Charitable Foundation, Fundació la Caixa, NYC Economic
US$ 500,000 to US$ 1 million
Development Corporation
US$ 250,000 to US$ 500,000 Foundation for the National Institutes of Health, GlaxoSmithKline, Google
amfAR, BMS Foundation, Broadway Cares/Equity Fights AIDS, Carlsberg
Foundation, Continental Airlines, EMMES Corporation, Hearst Foundation,
Institut Mèrieux, John D. Evans Foundation, John M. Lloyd Foundation,www.hivresourcetracking.org Investing to End the AIDS Epidemic: A New Era for HIV Research & Development 15
Johnson (through its subsidiary Crucell), Merck & Estimated Commercial Engagement in
Co., Novartis Vaccines and Sanofi Pasteur. Table 6
HIV Vaccine R&D by Company in 2011
In 2011, Johnson & Johnson acquired the Dutch US$5mn to GSK, Merck & Co., Novartis
biotechnology company, Crucell, which has been US$10mn International AG, Sanofi Pasteur
working in collaboration to evaluate its Ad26
adenovirus vector. With the Beth Israel Deaconess US$1mn to Crucell, ESTEVE, GeoVax,
Medical Center (BIDMC) and the Ragon US$5mn Mymetics
Institute, both in Boston, Massachusetts, and the
Walter Reed Army Institute of Research, in Silver Advanced BioScience, Argos
Spring, Maryland, Crucell has looked at several US$100K to Therapeutics, Bionor Immuno,
prime-boost vaccine combinations of Ad26. In US$1mn FIT-Biotech, Genvec, Ichor, Inovio
addition, Crucell, BIDMC, Ragon and the HVTN Pharmaceuticals, Vical
also have a collaboration with IAVI to conduct
a clinical study of a Ad26/Ad35 prime boost The third area of investigation of GSK’s program
regimen. GSK has a long history of HIV vaccine is early-discovery R&D to identify new envelope
R&D, beginning with the initiation of its vaccine antigen candidates in partnership with several
program in 1986. The company currently has three academic institutions.
areas of focus in the preventive HIV vaccine field. Merck, along with various partners, is working
The company is investigating an HIV-1 vaccine on an R&D program that aims to identify an
candidate containing a recombinant fusion protein HIV envelope–based protein vaccine capable
along with their proprietary adjuvant, AS01, in of producing broadly neutralizing antibodies
collaboration with IAVI. Additionally, with the against HIV infection. The company continues
Institut Pasteur, funded in part by the EC Sixth to analyze the results of the STEP trial, which
Framework Programme, GSK is investigating a tested its adenovirus-5 vaccine, and to explore
vaccine approach based on the measles vaccine. its implications for vaccine design, as well as
Box 1 HIVACAT Collaboration in Action
The Spanish HIVACAT program is a collaboration of two The collaboration’s success is due to local patient
academic research centers, a philanthropic foundation, a cohorts with data and sample base of 15 years, a high-
private pharmaceutical company and regional government acceptance of HIV vaccine trials in the population and a team
departments, working to design, develop and test potential of scientists from institutions and universities worldwide.
preventive and therapeutic vaccines for HIV for further The pharmaceutical firm ESTEVE has been involved from
development and regulatory approval. This public-private the initiation of this program in 2008, providing financial
partnership is made up of two research institutions in support for the research phase, as well as intellectual property,
Barcelona, Spain, the AIDS and Infectious Diseases Service preclinical and clinical development, regulatory affairs and
at Barcelona’s Hospital Clinic, (affiliated with the University good manufacturing practices expertise—totaling over
of Barcelona),, and the IrsiCaixa Institute for AIDS Research, US$7.6 million in four years.
(affiliated with the Autonomous University of Barcelona), the The program’s eight lines of investigation tackle some of
Fundació la Caixa, the pharmaceutical company ESTEVE, the challenges in both preventive and therapeutic HIV vaccine
and two departments of the government of the Generalitat de design, including cellular and humoral immunity to HIV and
Catalunya, the Department of Health and the Department of how they affect viral control, the impact of viral sequence
Economy and Knowledge. diversity and host genetics on vaccine immunogen design,
HIVACAT’s collaborations include global partnerships neutralizing antibodies and the function of dendritic cells. In
with institutions, agencies, universities and organizations in recent years, HIVACAT researchers have had active therapeutic
Australia, Canada, France, Germany, Italy, Japan, Mexico, Peru, vaccine candidates, with a number of candidates moving to
Netherlands, South Africa, Switzerland, the UK and the US. Phase I and II clinical trials.16 Investing to End the AIDS Epidemic: A New Era for HIV Research & Development www.hivresourcetracking.org
Box 2 Local Production newly infected STEP trial participants and found
that the Step vaccine had exerted pressure on the
The Italian Institute of Health (ISS) is set to fund a new genetic evolution of the virus.
United Nations Industrial Development Organization
Novartis Vaccines continues to research its
(UNIDO) project in South Africa that aims to strengthen the
alphavirus vector, and is developing different
local production of essential medicines and other health envelope proteins as well as adjuvants for use as
commodities. The project supports development of a a boost to ALVAC prime in the follow-up trials
network of clinical sites and good manufacturing practice to the Thai RV144 trial or with other candidates.
(GMP) compliance in the production of vaccines in South The company has supplied the envelope proteins
Africa, and it includes a therapeutic HIV vaccine clinical for the first phase of clinical testing of a preventive
trial developed by ISS. The US$1.25 million project will HIV vaccine study launched in June by the
be implemented with the South African government and National Center of the Istituto Superiore di Sanità
the Directorate General Development Cooperation of the (ISS) in Italy, part of a collaboration of the AIDS
Italian Foreign Ministry. The work in South Africa will be Vaccine Integrated Project (AIVP).25
coordinated with UNIDO’s ongoing global project, which
focuses on strengthening the local production of essential Sanofi Pasteur, the vaccines division of the Sanofi-
medicines in developing and least-developed countries.26 Aventis Group, is engaging in follow-up studies
to RV144 with multiple partners in Thailand and
South Africa. In 2011, Sanofi Pasteur signed an
the development of antigens to elicit protective agreement with Novartis Vaccines to collaborate
antibodies to HIV. Despite the disappointing on an HIV vaccine prime-boost regimen to build
results of the STEP trial, the data has continued and improve on the efficacy level obtained in the
to yield important findings. In February 2011, RV144 study in Thailand. The focus will be on
scientists from University of Washington, who the development and clinical evaluation of the
HIV prime-boost approach in South Africa and
were not affiliated with the STEP trial, analyzed
Thailand. Novartis Vaccines and Sanofi Pasteur
the genome sequences in HIV-1 isolated from
are working in partnership with the Pox-Protein
Figure 7 HIV Vaccine Expenditures from 2001–2011 (US$ millions)
$1,000 Total Vaccine Funding 961
Preclinical 933
$900 Basic Research 868 868 859
Clinical Trials 845
$800 Cohort Development
Policy
759
$700
614
US Dollars (millions)
$600
548 547
$500
$400 366
$300
$200
$100
0
2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011www.hivresourcetracking.org Investing to End the AIDS Epidemic: A New Era for HIV Research & Development 17
Figure 8 Investment in Therapeutic HIV Vaccines in 2010 and 2011 (US$ millions)
2010 Investment: US$ 11.6 million 2011 Investment: US$ 21.2 million
United States
European Commission $.05M
$.08M $.03M
United Kingdom $.54M
France $1.8M
$1.9M $1.4M $.15M
Canada $.14M
$2.8M $1.6M $.44M
$1.6M Estonia
$1.8M
Sweden
Australia
$13.1M
$4.9M Spain
Campbell Foundation
Gates Foundation
amfAR
Geovax
Public-Private Partnership (P5), which includes with a small decrease in preclinical research and an
the US NIAID, the BMGF, the HIV Vaccine increase in clinical research. Further information
Trials Network (HVTN) and the US MHRP. about the categories used to define R&D can be
found in the Appendix.27
Sanofi Pasteur also contributed expertise and
funding to the BMGF’s Collaboration for AIDS
Vaccine Discovery (CAVD) project, which 2.1.5 G lobal investments in
contributes funds, expertise and products to therapeutic HIV vaccine R&D
the EuroVacc Foundation, and is a member of
Therapeutic vaccines enhance immune responses
EuroNeut-41, the European consortium on
for HIV-positive individuals to help them better
neutralizing antibodies.
control infection. Investment toward research
for therapeutic HIV vaccines for HIV-positive
2.1.4 F unding allocations for individuals increased in 2011 to US$21.2 million,
HIV vaccine R&D a change of US$9.6 million from 2010.28
In 2011, spending by public and philanthropic Investment from public-sector sources increased.
sectors on preventive HIV vaccine R&D was Investors included the US NIH (62 percent),
allocated to five categories: basic research (27 France’s Institut Pasteur (8 percent), Australia’s
percent), preclinical research (39 percent), clinical National Health and Medical Research Council
trials (28 percent), cohort and site development (5 (NHMRC) (7 percent), the Australian Research
percent), and advocacy and policy (1 percent). The Council (ARC) (6 percent), the UK Medical
percentage distribution of investment among the Research Council (2 percent), the Canadian
five categories in 2011 was similar to that of 2010, Institutes for Health Research (CIHR) (1.418 Investing to End the AIDS Epidemic: A New Era for HIV Research & Development www.hivresourcetracking.org
percent), the Canadian HIV Vaccine Initiative In 2007 and 2008, Timothy Brown, the “Berlin
(1.2 percent) and the Swedish Research Council patient”, received two bone marrow transplants to
(SRC) and Estonia Research Council (less than treat his leukemia. The donor was among the one
one percent each). percent of Northern Europeans lacking the CCR5
protein on the surface of CD4 cells, without
Philanthropic sources began funding therapeutic
which the virus is unable to enter the cells. With
vaccine research, with funding from the BMGF,
an immune system resistant to HIV infection, the
the Campbell Foundation and amfAR (3 percent).
Berlin patient has been off of ARVs for almost five
Funding from pharmaceutical and biotechnology years. However, finding a donor with mutations in
companies is likely underrepresented, since only the CCR5 gene who’s also a good immunological
a few biotechnology firms reported their match for the patient is very difficult.
investment in 2011.29 Companies involved in
Another approach is to treat CD4 cells removed
R&D for therapeutic vaccines in 2011 include
from an HIV-positive individual with gene
Argos Therapeutics, Bionor Immuno, FIT
therapy in order to remove the CCR5 protein
Biotech, Genetic Immunity, GeoVax, GSK,
and to then infuse the treated cells back into the
Invio Pharmaceuticals, Profectus Biosciences
individual. In the case of the “Trenton patient,”
and VIRxSYS.
one month after treated cells were put back into
his body, the man was able to stop taking ART
2.2 G
lobal investments in for a short period. Other approaches include
cure research interventions to activate latent HIV virus in CD4
cells and other locations that have proven resistant
HIV cure research has been galvanized in recent
to ART. Complementary strategies, such as
years. Two approaches are being studied: a
therapeutic vaccines, that would attack latent HIV
sterilizing cure that would eradicate HIV from
once it becomes active, are being developed.
the body, and a functional cure that would
keep the patient healthy without drugs but not Pharmaceutical and biotechnology companies
eliminate the virus from the body. have invested in cure research. Multinational
Figure 9 Investment in Cure Research in 2010 and 2011 (US$ millions)
2010 Investment: US$ 4.9 million 2011 Investment: US$ 16.4 million
$.02M United States $.14M
$.05M $.3M $.03M
Sweden
$1.7M $.9M
$.9M
Australia
Sweden
Doris Duke
Charitable Foundation
$3.9M $13.4M
France
Gate Foundation
amfARwww.hivresourcetracking.org Investing to End the AIDS Epidemic: A New Era for HIV Research & Development 19
companies like Gilead, Tibotec and Merck, as 2.3 G lobal investments in
well as biotechnology firms like Calimmune and microbicide R&D
Sangamo BioSciences, have started to increase
their efforts. Merck’s vorinostat, used to treat a Over the past 10 years, global investment in
rare cancer, is being tested in an early-stage clinical microbicide R&D has reached a total of nearly
trial. Another Merck candidate in preclinical trials US$2 billion, with an average yearly investment
is an antibody that blocks a protein called PD-1, of US$196 million. Total global investment in
associated with HIV latency. microbicide R&D was US$186 million in 2011.
Of the 2011 total, the public sector provided
NIAID awarded grants under the Martin Delaney US$176 million (95 percent); the philanthropic
Collaboratory totaling nearly US$70 million over sector, US$9 million (5 percent); and the
five years to three research teams in pursuit of cure commercial sector, US$1 million (20 Investing to End the AIDS Epidemic: A New Era for HIV Research & Development www.hivresourcetracking.org
Figure 10 Microbicide Funding from 2000–2011 (US$ millions)
$300 Commercial
Philanthropic
Public
$250 3 1
1
5 16
5 35 12
19
$200 26
1
US Dollars (millions)
5 9
$150 21
18
$100 17
25
3
$50 29
36 62 81 90 124 143 192 203 207 223 230 176
0
2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011
Table 8 Top Microbicide Funders for 2010 and 2011 (US $millions) 30
2010 Rank Funder Amount 2011 Rank Funder Amount
1 NIH 147.0 1 NIH 111.8
2 USAID 38.0 2 USAID 36.0
3 DFID 16.5 3 South African DST/DOH 10.0
4 BMGF 15.7 4 BMGF 7.0
5 EC 6.7 5 DFID 3.2
6 China 3.6 6 Netherlands 2.7
7 UK MRC 3.4 7 NORAD (Norway) 2.5
8 NORAD (Norway) 3.3 8 Wellcome Trust 1.6
9 EDCTP 2.0 9 Irish Aid 1.4
10 Spain 1.9 10 UK MRC 1.3
11 Netherlands 1.7 11 Denmark 0.9
12 Denmark 1.7 12 NHMRC 0.6
13 Germany 1.3 13 OFID 0.5
14 Irish Aid 1.1 14 Spain 0.4
15 CDC 0.7 15 ARC 0.4www.hivresourcetracking.org Investing to End the AIDS Epidemic: A New Era for HIV Research & Development 21
funders, such as the OPEC Fund for International of 1% tenofovir gel, there is increasing clarity
Development (OFID) and the M.A.C. AIDS Fund, about next steps, along with new questions. In
contributed over US$500,000 in 2011. OFID’s total June 2011, USAID distributed a discussion draft
grant for microbicide research was US$1.5 million, of a strategic plan for microbicide introduction,
to be allocated over the next few years. and the South African and US governments
announced full funding for the confirmatory
multisite FACTS 001 trial, testing 1% tenofovir
2.3.1 P ublic investments in gel. With FACTS 001 scheduled to release results
microbicide R&D on the safety and effectiveness of 1% tenofovir
In 2011, public-sector investment accounted for gel in 2014, and the open-label implementation
95 percent of the combined global funding for study CAPRISA 008, which is evaluating the
microbicide research, development and advocacy. effectiveness of distributing 1% tenofovir gel in
The US continues to be the primary source of communities where CAPRISA 004 took place,
funding at US$148 million, representing 80 releasing results in 2013, advancements are being
percent of total funding for microbicide R&D. made in the microbicide field.
US funding decreased by over US$39 million In November 2011, the field received
in 2011, a 21 percent drop. In 2010, the final disappointing news regarding the 1% tenofovir
disbursement of ARRA stimulus funds accounted gel arm of the large-scale VOICE trial. The arm
for US$4.5 million of NIH investment in was dropped for futility after an independent Data
microbicide R&D, which explains in part the and Safety Monitoring Board (DSMB) review
drop-off in US funding for 2011. European found no effect in preventing HIV. The trial used
national governments and the EC together a different dosing strategy from that of CAPRISA
accounted for US$16 million (9 percent), a 004 and FACTS 001; participants were counseled
US$24.3 million (60 percent) decrease from 2010. to use the gel daily as opposed to before and after
As the field moves further from the results of the sex. In September 2011, the oral tenofovir arm
CAPRISA 004 trial, which tested the effectiveness of the VOICE trial was also stopped after the
Figure 11 Microbicide Funding from 2000–2011 (US$ millions)
$300 Total Microbicide Funding
Total Public
G8
G20 247
$250 244
Philanthropic 236
222 227
$200
US Dollars (millions)
186
169
$150 147
106 107
$100
65 65
$50
0
2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 201122 Investing to End the AIDS Epidemic: A New Era for HIV Research & Development www.hivresourcetracking.org
DSMB determined that it was not effective in the of some candidates as MPTs. An “integrated
context of the trial. MPT pipeline” that includes contraceptive
agents and delivery systems, HIV entry and
The microbicide field continues to advance other
enzyme inhibitors and non-HIV anti-infective
candidates, with a robust pipeline of options that agents, is under review. The MPT pipeline is now
include a vaginal ring and rectally applied gel. integrated into US NIH and USAID strategies,
The International Partnership for Microbicides and is being examined by the BMGF as an
(IPM) launched a clinical trial assessing the long- investment option. China is evaluating a CCR5
term safety and efficacy of a vaginal ring with antagonist–based gel formulation in preclinical
the ARV dapivirine (The Ring Study), and the studies with funding from the Chinese Ministry
US NIH–funded Microbicide Trials Network of Health, Ministry of Science and Technologies
(MTN) planned to start a parallel study of the and private sector; India’s ICMR is pursuing
dapivirine ring (ASPIRE). IPM and MTN are preclinical and clinical studies of other drug
also collaborating on a Phase I study of maraviroc- substances; and the Combined Highly Active
based vaginal rings: a ring containing maraviroc Anti-Retroviral Microbicides (CHAARM) project,
alone and a combination dapivirine-maraviroc a large collaboration co-funded by the EU under
ring. A study testing 1% tenofovir gel used rectally the Seventh Framework Programme, continues
is scheduled to begin in early 2013.31 Looking its wide-ranging basic research into specifically
ahead, the field has a number of late-stage studies targeted combinations for topical application.
set to begin.
A considerable research effort is being made 2.3.2 P
hilanthropic investments in
to study a variety of other microbicide delivery microbicide R&D
systems, as well. The MTN 005 open-label trial,
now enrolling, will test a placebo vaginal ring in In 2011, the philanthropic sector provided US$9
an early-stage safety, adherence and feasibility million (5 percent) of the funds disbursed for
study in India and two US sites, a collaboration microbicide R&D. The investment in 2011
between the Population Council and two NIH represented a 42 percent decline from 2010, due
institutes. Both CONRAD and the Population in part to timing shifts in the investments of
Council are developing protocols for early clinical some funders. As in 2010, the majority of funding
studies of combination approaches, increasingly came from the BMGF and the Wellcome Trust.
referred to as “dual-protection” or “multipurpose However, in 2011 the funder portfolio grew more
technologies” (MPTs). Examples of these are diverse, with two new funders, the M.A.C. AIDS
the SILCS diaphragm and ARV-based gels, Fund and OFID, investing in microbicide R&D.
intravaginal rings (IVRs) and tablets combining
ARVs and contraceptive agents, as well as a range
of different dosing regimens for both ARV-based
2.3.3 C
ommercial investments
and contributions to
and combination ARV/contraceptive strategies,
including dual-protection injectables. Finally, there
microbicide R&D
are a range of studies exploring different aspects Total commercial-sector microbicide investment
of microbicide safety, acceptability and adherence in 2011 was estimated at US$1 million, mostly
in both early clinical trials and discrete studies from biotechnology firms, with some large
that include a pregnancy exposure registry, a cross- pharmaceutical investment, as well. As has been
sectional resistance study, a bone mineral density the case throughout the history of R&D for
sub-study, as well as feasibility studies in different microbicides, the most significant contributions
populations, including sex workers, and a follow-up from the private sector were royalty-free transfers
of HIV-1 seroconversion in microbicide trials. of ARVs for use as active agents in microbicide
While funding for basic research decreased development. Microbicide developers continue to
between 2010 and 2011, candidates in the receive product information and technical support
preclinical microbicide pipeline are receiving and advice from commercial partners. CONRAD,
selective attention, with a focus on the potential the Population Council and IPM also receivedwww.hivresourcetracking.org Investing to End the AIDS Epidemic: A New Era for HIV Research & Development 23
royalty-free licenses and material transfers from formulations and modes of delivery (7 percent),
pharmaceutical companies, including licenses to clinical trials (48 percent), microbicide behavioral
develop ARVs as components of combination and social science research (3 percent), microbicide
products. The biotechnology industry, through research infrastructure (7 percent), and policy and
a variety of grant and contract mechanisms, has advocacy (4 percent).33
developed both ARV- and non-ARV-based
Preclinical testing and clinical trials remained
products. Mapp Biopharmaceutical is engaged in
the categories with the largest expenditures.
R&D for microbicides using monoclonal antibodies.
Preclinical work declined from 25 percent in 2010
The contribution of companies is not readily to 22 percent in 2011, as did research on basic
quantifiable, but includes a range of expertise and mechanisms of mucosal transmission, from 18
support such as legal support for material transfer percent in 2010 to 8 percent in 2011. There is
agreements and licenses; regulatory and scientific hope that upcoming NIH funding announcements
advice; access to toxicology studies and safety will infuse new investment and energy into this
data from clinical trials or surveillance; grants early research, since a number of fundamental
of product and product remanufacturing; advice questions remain regarding both topical and oral
regarding manufacture of microbicide delivery microbicides for PrEP. Not surprising, a large
systems; participation in development meetings increase was seen in clinical trial expenditures,
and teleconferences; and, timeline guidance.32 which rose from 38 percent in 2010 to 48 percent
in 2011. Increases were also seen in allocations for
formulations and modes of delivery, as well as for
2.3.4 F unding allocations for
and behavioral and social science research.
microbicide R&D
In 2011, expenditures on microbicide R&D were
2.3.5 I nvestments in rectal
allocated across the following seven categories:
microbicide R&D
basic mechanisms of mucosal transmission
(8 percent), preclinical testing (22 percent), In 2011, R&D toward a rectal microbicide was
funded at approximately US$4.1 million. Between
2001 and 2011, global spending
Figure 12 Microbicide Expenditures from 2006–2011 (US$ millions) on rectal microbicide research
totaled US$30 million. In
$250 244 247
236
2011, the majority of funding
222
227 came from US sources and
was dedicated to support
$200 preclinical development of
186 rectal microbicide products
and clinical testing of rectal
US Dollars (millions)
$150
microbicides.
Most of this work is funded
by the NIH which, in 2009,
$100 established the Combination
Total Microbicide
Funding HIV Antiretroviral Rectal
Basic Mechanisms Microbicide Program
Preclinical
Formulations
(CHARM), a five-year, US$11
$50
Clinical Trials million, multi-center grant
Behavioral intended to advance candidate
Infrastructure
rectal microbicides from
Policy & Advocacy
0 discovery into early clinical
2006 2007 2008 2009 2010 2011 development. CHARM
works through a multi-sectorYou can also read
