[Senate Prints 109-44]
[From the U.S. Government Publishing Office]


109th Congress                                                  S. Prt.
                            COMMITTEE PRINT                     
 1st Session                                                     109-44
_______________________________________________________________________

                                     


 
                    2005 AIDS VACCINE INTERNATIONAL
                     CONFERENCE, MONTREAL, CANADA,
                          SEPTEMBER 6-9, 2005



                               __________

                           STAFF TRIP REPORT

                                 TO THE

                     COMMITTEE ON FOREIGN RELATIONS

                          UNITED STATES SENATE

                       One Hundred Ninth Congress

                             First Session

                             December 2005

                                     



                    U.S. GOVERNMENT PRINTING OFFICE
25-334                      WASHINGTON : 2005
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                     COMMITTEE ON FOREIGN RELATIONS

                  RICHARD G. LUGAR, Indiana, Chairman

CHUCK HAGEL, Nebraska                JOSEPH R. BIDEN, Jr., Delaware
LINCOLN CHAFEE, Rhode Island         PAUL S. SARBANES, Maryland
GEORGE ALLEN, Virginia               CHRISTOPHER J. DODD, Connecticut
NORM COLEMAN, Minnesota              JOHN F. KERRY, Massachusetts
GEORGE V. VOINOVICH, Ohio            RUSSELL D. FEINGOLD, Wisconsin
LAMAR ALEXANDER, Tennessee           BARBARA BOXER, California
JOHN E. SUNUNU, New Hampshire        BILL NELSON, Florida
LISA MURKOWSKI, Alaska               BARACK OBAMA, Illinois
MEL MARTINEZ, Florida
                 Kenneth A. Myers, Jr., Staff Director
              Antony J. Blinken, Democratic Staff Director

                                  (ii)




                            C O N T E N T S

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                                                                   Page
Letter of Transmittal............................................     v

Conference Overview..............................................     1

    Scientific Challenges to Developing an Effective HIV Vaccine.     1

    Efforts to Coordinate AIDS Vaccine Research..................     3

    Other Challenges in the Pursuit of an Effective AIDS Vaccine.     3

Concluding Thoughts and Recommendations..........................     6

                                 (iii)




                         LETTER OF TRANSMITTAL

                              ----------                              

                                                  December 28, 2005
Hon. Richard G. Lugar, Chairman,
U.S. Senate Committee on Foreign Relations.

Dear Senator Lugar:

    On behalf of the Senate Committee on Foreign Relations, I 
traveled to Montreal, Canada from September 6-9, 2005. The 
purpose of this trip was to attend the 2005 AIDS Vaccine 
International Conference.
    The trip afforded me the opportunity to learn about the 
latest scientific progress in developing an AIDS vaccine, 
better understand the myriad social issues surrounding this 
work, and consult with key individuals working on this issue. 
Attached is a summary of the trip and a discussion of the 
impressions and conclusions developed throughout the trip. The 
conclusions in this report are my own and do not necessarily 
reflect the views of the Committee on Foreign Relations or its 
members.
            Sincerely,
                                 Chris Ann Keehner,
                                   Counsel, Majority Staff,
                        U.S. Senate Committee on Foreign Relations.


                                  (v)



                    2005 AIDS VACCINE INTERNATIONAL
                     CONFERENCE, MONTREAL, CANADA,
                         SEPTEMBER 6-9, 2005

                              ----------                              


                          Conference Overview

    Despite the dramatic increase in funding in the last few 
years for programs to prevent the spread of the human 
immunodeficiency virus (``HIV'') and to treat those living with 
the acquired immune deficiency syndrome (``AIDS''), the spread 
of the disease continues to outpace us. According to UNAIDS, 
there are an estimated 40.3 million people living with HIV 
today. Over three million people died of AIDS in 2005, and 
nearly 4.9 million people became infected with HIV this year. 
This means that every day around the globe, some 14,000 people 
are newly infected with HIV. In addition, experts are concerned 
about a possible ``second wave'' of countries with AIDS 
epidemics, including Russia, China, India, Nigeria, and 
Ethiopia.\1\
---------------------------------------------------------------------------
    \1\ For more information on the current state of the AIDS pandemic, 
see the UNAIDS/WHO AIDS Epidemic Update: December 2005, which can be 
found at http://www.unaids.org.
---------------------------------------------------------------------------
    Getting ahead of this pandemic--through current prevention 
and treatment programs alone--will continue to be a challenge. 
An effective AIDS vaccine holds promise to be the world's best 
chance to stop this pandemic. Historically, vaccines have led 
to some of the greatest achievements in public health and are 
among the most cost-effective health interventions. During the 
20th century, global immunization efforts have successfully led 
to the eradication of smallpox and the elimination of polio 
from the Western Hemisphere, Europe, and most of Asia. Vaccines 
for diseases such as measles and tetanus have dramatically 
reduced childhood mortality worldwide, and vaccines for 
diseases such as influenza, pneumonia, and hepatitis now help 
prevent the sickness and death of adults, too.
    The theme of the 2005 AIDS Vaccine International Conference 
was ``Together, A Better Future for All,'' and was held in 
Montreal, Canada. The Conference brought together scientists, 
policy makers, and activists from around the world with a 
special interest in the development of vaccines to prevent HIV 
and AIDS. The Conference provided a unique opportunity to learn 
about the most recent scientific progress in developing an AIDS 
vaccine and the social, ethical, and economic issues 
surrounding the pursuit of this goal.


      SCIENTIFIC CHALLENGES TO DEVELOPING AN EFFECTIVE HIV VACCINE


    There are currently about 30 candidate AIDS vaccines in 
clinical testing around the world today. The immediate goal of 
AIDS vaccine research is to design candidate vaccines that 
trigger responses from both the major arms of the body's immune 
system--humoral immunity and cellular immunity. Humoral 
immunity involves the creation of antibodies that recognize and 
attack a pathogen--like HIV--in the blood and prevent it from 
infecting the body's cells. Cellular immunity is triggered once 
the pathogen has infected some of the body's cells, and its 
role is to recognize and destroy infected cells to prevent 
further spread of the pathogen.\2\
---------------------------------------------------------------------------
    \2\ For a more in-depth discussion of immunology and vaccine 
development with respect to an AIDS vaccine, see the AIDS Vaccine 
Advocacy Coalition's (AVAC) AIDS Vaccine Handbook (2d ed. 2005). The 
full text of the book is available online at http://www.avac.org.
---------------------------------------------------------------------------
    The complicated nature of HIV, however, creates significant 
scientific challenges for researchers. One of these challenges 
is the way HIV interacts with the human immune system. Most 
vaccines work by triggering the body's immune system to produce 
antibodies against infection. The antibodies search out 
invaders in the bloodstream--like viruses or bacteria--and 
attack them. HIV, however, is extremely adept at evading the 
immune system, thus making this approach to an AIDS vaccine 
especially challenging. Determining how to design vaccines that 
stimulate an antibody-producing response is a priority for 
scientists. If a vaccine were able to produce this response, it 
would block HIV infection altogether. Although most researchers 
agree that solving this problem is essential to developing an 
AIDS vaccine, so far, trials have been unsuccessful in creating 
an antibody response.
    Because of the difficulty in discovering a vaccine that 
triggers an antibody-producing effect, most of the current 
trials focus on cellular immunity, which if successful, might 
not prevent an individual from getting HIV, but would delay or 
prevent the progression of the disease and reduce transmission. 
Researchers are closely watching the clinical trials of Merck & 
Company, which has initiated a candidate aimed at stimulating 
cellular immunity. This ongoing study is testing the company's 
lead vaccine candidate known as ``MRKAd5'' in approximately 
3,000 volunteers. This trial will test the hypothesis that a 
vaccine based on portions of genetic material from HIV can 
stimulate cellular immunity to prevent HIV disease, and perhaps 
infection. This trial is being conducted in sites in the United 
States, Australia, the Caribbean, and Latin America. The 
results of this important trial are anticipated in 2007 at the 
earliest, and will likely shape the direction of future AIDS 
vaccine research.
    Another complicating factor is HIV's diversity. There are 
several strains of HIV and the virus is constantly generating 
new ones. Globally, six different strains account for the 
majority of HIV infections. This means that scientists need to 
find vaccines that induce immunity against the broadest range 
of these HIV strains.
    Given the scientific challenges of developing an effective 
HIV vaccine, researchers in the field are modifying the 
traditional vaccine development process. Normally, clinical 
trials are conducted in three phases. Phase I trials typically 
involve several dozen volunteers at low risk for HIV infection 
and test whether the vaccine triggers an immune response. Phase 
II trials involve several hundred volunteers, including some at 
high risk for HIV infection, and gather both safety and 
immunogenicity\3\ data. Phase III efficacy trials enroll 
thousands of participants and seek statistical determinations 
of whether a vaccine is effective. Very few of the vaccines 
tested will make it to Phase III testing. Although there have 
been dozens of different AIDS vaccines tested in Phase I 
trials, only three have made it into Phase III. Because of the 
high cost in taking a vaccine all the way to Phase III trials, 
AIDS vaccine developers have added a fourth phase to the 
process: Phase IIb or ``proof of concept'' trials. The goal 
behind this new phase is to look for preliminary evidence of 
efficacy in smaller, shorter, and far less expensive trials 
before engaging in a Phase III trial. (The Merck trial studying 
cellular immunity is a Phase IIb trial.)
---------------------------------------------------------------------------
    \3\ When collecting data on immunogenicity, researchers are 
examining the strength and breadth of the immune response of a trial 
vaccine.
---------------------------------------------------------------------------


              EFFORTS TO COORDINATE AIDS VACCINE RESEARCH


    Because of the complicated nature of AIDS vaccine research, 
most experts agree that there is a need for a much larger-
scaled, better-coordinated, better-funded effort, consisting of 
researchers from different organizations working together to 
solve given scientific problems. Ideally, each of these 
organizations would contribute its special expertise and would 
share the information it discovers. Speakers at the Conference 
discussed how efforts to better coordinate AIDS vaccine 
initiatives have improved significantly over the past two 
years. For instance, the Global HIV Vaccine Enterprise 
(``Enterprise''), which was first proposed in Science magazine 
in June 2003 and established in 2004, is a ``virtual 
consortium'' of scientists, advocates, and other stakeholders 
organized to accelerate research efforts to develop an AIDS 
vaccine. In February 2005, the Enterprise published the 
Scientific Strategic Plan, a blueprint outlining the major 
scientific hurdles to be overcome in the development of an AIDS 
vaccine.\4\ The Enterprise's first Stakeholders' Forum was held 
in London on May 23-24, 2005, organized by the U.K. Department 
for International Development and the Bill & Melinda Gates 
Foundation. In October, the Enterprise held its first Funders' 
Forum. Currently, the Bill and Melinda Gates Foundation is 
acting as interim Secretariat, and the Enterprise is in the 
process of selecting an Executive Director.
---------------------------------------------------------------------------
    \4\ For more information on the Global HIV Vaccine Enterprise, see 
http://www.hivvaccineenter-prise.org.
---------------------------------------------------------------------------
    On the domestic front, Dr. Anthony S. Fauci, Director of 
the National Institute of Allergy and Infectious Diseases at 
the National Institutes of Health, spoke at the Conference 
about the Partnership for AIDS Vaccine Evaluation (``PAVE''), 
the interagency group coordinating AIDS vaccine research among 
the Department of Defense, the Centers for Disease Control, the 
National Institute of Allergy and Infectious Diseases, and 
other agencies and offices. In addition, the Center for HIV/
AIDS Vaccine Immunology (``CHAVI'') was established by 
President Bush last year, and is a consortium of universities 
and academic medical centers organized by the National 
Institute of Allergy and Infectious Diseases (NIAID) under Dr. 
Barton Haynes of Duke University. It is intended to solve major 
problems in AIDS vaccine development and to be a component of 
the Global HIV Vaccine Enterprise.\5\ The CHAVI has received a 
seven-year grant of $300 million for AIDS vaccine research and 
plans on holding its first clinical trials in 2007. In addition 
to federal funding for AIDS vaccine research, the Bill and 
Melinda Gates Foundation has allocated $360 million for grants 
in the context of the scientific plan of the Global HIV Vaccine 
Enterprise.
---------------------------------------------------------------------------
    \5\ For more information on the CHAVI, see http://www.chavi.org.
---------------------------------------------------------------------------


      OTHER CHALLENGES IN THE PURSUIT OF AN EFFECTIVE AIDS VACCINE


    Apart from the scientific challenges researchers face in 
developing an effective AIDS vaccine, there are several other 
issues that create tremendous hurdles in this field.
Increasing Private Sector Investment in AIDS Vaccine Research
    One of the biggest challenges is the lack of private sector 
investment in research and development of an AIDS vaccine. 
There are two main reasons for this. First, many pharmaceutical 
companies have ceased to invest in research and development of 
vaccines, due to the liability risks involved and the lower 
profit margin of vaccines compared to medicines taken to treat 
chronic illnesses. Representatives of the private sector spoke 
at the Conference about the tremendous costs involved in 
bringing a product to market, and explained that most 
medications are far more profitable than vaccines, which are 
typically administered only once. Second, when the target 
population for a new product, such as an AIDS vaccine, lives 
largely in the developing world, there is essentially is no 
viable commercial market to entice research and development in 
the production of the product.\6\
---------------------------------------------------------------------------
    \6\ For a more thorough discussion of the challenges faced in 
encouraging increased private sector research and development for 
vaccines for diseases endemic to developing countries, see Making 
Markets for Vaccines: Ideas to Action, by Ruth Levine, Michael Kremer, 
and Alice Albright of the Center for Global Development. This report 
can be accessed at http://www.cgdev.org.
---------------------------------------------------------------------------
    In order to fill this economic gap, experts are developing 
various incentives to motivate the private sector to invest in 
research and development for vaccines to prevent diseases, like 
HIV, that are predominately found in the developing world. 
Among these incentives are tax credits, ``wild card'' patent 
extensions, and advanced market commitments. Public-private 
partnerships have also proved beneficial in the pursuit of 
vaccines for diseases of developing countries, and experts are 
seeking ways to increase these partnerships.\7\
---------------------------------------------------------------------------
    \7\ In September, Senators John Kerry (D-MA) and Richard Lugar (R-
IN) introduced the Vaccines for the New Millennium Act of 2005, a bill 
that seeks to accelerate efforts to develop vaccines for HIV/AIDS, 
tuberculosis, malaria and other diseases in developing countries. 
Representative Pete Visclosky (D-IN) introduced companion legislation 
in the House of Representatives. See S. 1698 and H.R. 3781.

The Challenges of Conducting Vaccine Trials in Developing
    Countries

    Because the majority of people with HIV and AIDS live in 
developing countries, it is essential that vaccine trials be 
conducted in these countries to ensure an effective vaccine. 
Conducting vaccine trials in underdeveloped countries, however, 
is especially challenging for a variety of reasons. The biggest 
challenge to conducting trials in these countries is the lack 
of health care infrastructure and trained personnel. In 
addition, in order for trials to be successfully carried out 
and understood by volunteers participating in them, there is a 
need for political leadership supporting the trials, and for 
countries to develop national AIDS vaccine plans. Finally, 
volunteers participating in vaccine trials need access to 
treatment and counseling programs, and to the extent possible, 
these trials should be coordinated with such programs funded by 
the President's Emergency Plan for AIDS Relief and the Global 
Fund.
    One of the ethical issues raised at the Conference 
concerned informed consent among vaccine trial participants in 
developing countries. Generally, it is recommended that an 
individual have a sixth grade education level for all informed 
consent processes. This standard is inapplicable in much of 
Africa, where most of the population is illiterate. In 
addition, in countries where participants' beliefs about health 
and illness differ from those of scientists, it is critical 
that researchers be sensitive to local beliefs, values, and 
practices. It is important that researchers use local language 
and concepts in explaining vaccine trials and ensuring that 
participants truly understand how trials work. Some cultures 
are far less individualistic than Western cultures, and the 
needs of the community outweigh often those of the individual. 
In these situations, researchers are developing methods to 
ensure that the decision to participate in a trial is made by 
an individual and not by a community leader or representative. 
Given the challenges of illiteracy and cultural differences, 
experts are continuing to explore the best methods to ethically 
obtain informed consent in developing countries.

The Importance of Including Women, Adolescents, and Children in
    Clinical Trials

    To date, AIDS vaccine trials have focused almost 
exclusively on adults. However, given the alarmingly high HIV 
prevalence rates in adolescents--especially females--in Sub-
Saharan Africa, some experts argue that the ideal AIDS vaccine 
would target adolescents, prior to their sexual debut. \8\ In 
addition, a vaccine for infants could help prevent the 
transmission of HIV through breast milk, which is the primary 
source of nourishment for most newborns in the developing 
world. Many experts in the field agree that an AIDS vaccine 
must ultimately include children, but that conducting the 
necessary research raises a host of scientific and ethical 
concerns. Because women and girls constitute the fastest 
growing population in Sub-Saharan Africa to become infected 
with HIV, it is imperative that the scientific community ensure 
the inclusion of women in the pursuit of an AIDS vaccine.
---------------------------------------------------------------------------
    \8\ According to UNAIDS, in 2005 in Sub-Saharan Africa, among young 
people aged 15-24 years, an estimated 4.6% of women and 1.7% of men 
were living with HIV. See UNAIDS/WHO AIDS Epidemic Update, December 
2005, p. 17.
---------------------------------------------------------------------------
    Enrolling children and adolescents in such trials, however, 
is controversial because in many places, this would clash with 
cultural beliefs against discussing sex with young people and 
in acknowledging their sexual activity and risk of HIV 
infection. In addition, government officials may be hesitant to 
advocate for the involvement of children in trials as 
communities may be suspicious and fearful of allowing their 
children to serve as ``guinea pigs.'' The issue of ``informed 
consent,'' already a challenge when dealing with adult 
participants in clinical trials, would be event more 
complicated when dealing with minors. The issue of including 
children and minors in clinical trials will require further 
debate by AIDS vaccine researchers, and the concerns of 
representatives from developing countries must be considered.
Regulatory Issues
    Finally, one of the issues raised by speakers at the 
Conference was the issue of regulating AIDS vaccines. 
Currently, there is no consensus as to what properties an AIDS 
vaccine will need in order to be granted a license. Given the 
variety of strains of HIV, it is also not clear whether 
countries will require a vaccine that has been proven effective 
in one or several regions to be tested again in local 
populations or against certain strains. Moreover, each country 
or region has its own licensing authority with its own 
requirements. Therefore, it will be impossible for vaccine 
producers to apply for a single license that is valid 
everywhere.
    Regulatory agencies in developing countries often lack the 
capacity to review new products, such as an AIDS vaccine. 
Authorities in these countries will likely look to developed 
countries or the World Health Organization for guidance in 
licensing a particular AIDS vaccine but, as has been the case 
with the regulation of anti-retroviral drugs, each country will 
ultimately need to reach its own conclusions. AIDS vaccine 
researchers, activists, and policy makers need to begin to 
consider how to streamline the regulatory process for an AIDS 
vaccine so as to prevent the delay in distribution of a vaccine 
once one is developed.

                Concluding Thoughts and Recommendations

    Given the rate at which the HIV/AIDS pandemic continues to 
spread around the world, and with growing concerns about 
``second wave'' countries like Russia, India, China, Nigeria, 
and Ethiopia, it is critical that a way to prevent the spread 
of this disease is found. The best hope for such prevention is 
a vaccine. Although the biggest hurdles to the development of 
an effective AIDS vaccine are scientific, more needs to be done 
to accelerate the research behind this effort and to address 
the non-scientific hurdles to developing such a vaccine. Donors 
should collaborate so that AIDS treatment, counseling, and 
testing programs support on-going vaccine trials. Activists and 
policymakers need to work with the private sector to implement 
meaningful incentives that will create viable markets and 
encourage increased private sector activity in this area. 
Although experts agree that an effective AIDS vaccine is 
possible, it will take a greater commitment from a range of 
governments, organizations, scientists and committed 
individuals to create a vaccine to end the AIDS pandemic.

                                 
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