RESEARCH AND TRIALS
Challenges highlighted at AIDS Vaccine 2003
GLOBAL NEWS
AIDS Vaccines at ICASA
SPOTLIGHT
The search for an AIDS vaccine in Russia
PRIMER
Understanding routes of transmission: Why do vaccines need to be tested in different populations?
RESEARCH AND TRIALS
Challenges highlighted at AIDS Vaccine 2003
Coordination and challenges were major themes at the AIDS Vaccine 2003 conference held 18-21 September in New York City, an annual meeting sponsored by the US National Institutes of Health, the French research program ANRS, and the World Health Organization. The meeting featured updates on vaccine science and clinical trials. Many presentations described continuing progress in these areas but there were no major breakthroughs announced. Instead participants reflected on the challenges facing the AIDS vaccine field and emphasized the need for continued work on ‘basic science’ (laboratory studies of vaccines and immune responses), clinical trials site development, and studies aimed at finding a correlate of protection that could be used to swiftly identify effective vaccines in animal and human studies. Gary Nabel, head of the US Vaccine Research Center, said that a trial that identified a correlate of protection would be a “transforming event” for the field.
Many speakers emphasized the need for increased collaboration and coordination between US and Europe and between the industrialized world and developing countries. “We need teams of the best and brightest people working in problem-solving mode to overcome scientific obstacles,” said IAVI’s Senior VP for Research and Development Wayne Koff.
One source of this coordination could be the Global HIV Vaccine Enterprise which was recently proposed by a coalition of vaccine researchers, including Richard Klausner of the Bill & Melinda Gates Foundation. Larry Corey, head of the US HIV Vaccine Trials Network, reviewed planning activities for the Enterprise including an August meeting in Washington DC. At that meeting working groups on regulatory issues, organization and funding, clinical trials capacity, manufacturing issues, product development, and vaccine discovery were formed. These groups will help develop a plan for action.
Corey said that “the real challenge and real work will be to get agreement that there is a good enough plan [from the working groups] … so that the people who actually provide the money agree” that there is broad support from AIDS vaccine developers. The enterprise has not yet received any funding and does not have a set membership. Jose Esparza, head of the WHO-UNAIDS Joint Vaccine Initiative, emphasized the openness of the project. “The Enterprise doesn’t exist beyond a vision. It is not an organization. This is not a club,” he said. “The intention is to involve the whole community globally.”
GLOBAL NEWS
AIDS Vaccines at ICASA
On 20 September nearly 100 African scientists, trial volunteers, community advisory board members and AIDS NGO representatives from Africa participated in “Community Matters: Preparing for a Vaccine to Prevent AIDS,” an all-day workshop on the ethics and science of AIDS vaccine development co-sponsored by IAVI, AfriCASO, ICASO, KANCO and AAVP. The workshop was an official satellite of the International Conference on AIDS and Sexually Transmitted Diseases in Africa (ICASA) held in Nairobi from 21-26 September. Kenyan Minister of Tourism and Information Raphael Tuju opened the satellite session and reminded the audience that “no epidemic of this magnitude has ever been rolled back without a vaccine.” He urged African AIDS organizations, governments and research groups to place AIDS vaccine research on their agendas alongside treatment, condoms and other prevention strategies.
The satellite meeting featured an in-depth discussion of new policies on treatment for HIV-negative vaccine trial volunteers who become infected with HIV through high-risk behavior during the study. (AIDS vaccines cannot cause HIV infection but some volunteers may become infected with HIV during the course of a study through their high-risk behavior.) Representatives from HIV Vaccine Trials Network, IAVI and the South African AIDS Vaccine Initiative each outlined policies that include payment for several years of antiretroviral therapy for volunteers who become infected during AIDS vaccine trials. Other sessions explored ways to explain AIDS vaccine research to nonscientific audiences. This topic was also examined at an IAVI-sponsored skills building workshop on AIDS vaccine materials and education programs on 22 September.
IAVI President and CEO Seth Berkley facilitated an AIDS vaccine “roundtable” discussion at the main conference. Berkley highlighted the accomplishments of Uganda and Kenya which were the first African countries to approve and complete AIDS vaccine trials, saying “East Africa has shown remarkable commitment and leadership on AIDS vaccines. These efforts should be applauded and expanded so that we move as rapidly as possible towards an effective AIDS vaccine, which is so desperately needed in these countries and in the rest of the world.”
SPOTLIGHT
The search for an AIDS vaccine in Russia
Today, Russia is at the heart of the fastest growing AIDS epidemic in the world. It is an epidemic that is spreading mainly through intravenous drug use. (Intravenous drug users (IDUs) sometimes share needles that have been contaminated with HIV-infected blood and this leads to new infections.) In some parts of Russia more than 60% of IDUs are infected with HIV and the epidemic is not showing any signs of slowing down. Between 1998 and 2002, for example, there was a 22-fold increase in HIV among pregnant Russian women. If this epidemic continues unchecked, experts warn that 1 in 25 Russians could be HIV positive by 2008.
At first glance there is reason to hope that Russia can respond to its epidemic. The country has a large number of doctors and nurses and well-developed systems for conducting scientific research and approving new products. It is also a country with a long history of developing and manufacturing its own vaccines and medications. During the Soviet era, for example, Russian facilities produced one-third of the supplies of smallpox vaccine used in the worldwide campaign to wipe out the disease.
Many of the Soviet era vaccine manufacturing plants are now out of date and do not meet international standards. But these facilities and their staffs are still a potential foundation for AIDS vaccine efforts. A small group of Russian researchers and international collaborators are now attempting to build on this foundation to respond to the explosive AIDS epidemic there.
It is a challenging task. Russia has been slow to respond to its epidemic. President Vladimir Putin has yet to make an urgent call for a coordinated response to the crisis and government funding levels for AIDS treatment and care remain low. One reason for the slow response may be the public opinion that AIDS is limited to highly-stigmatized groups of people like IDUs and commercial sex workers. In fact the disease is not confined to isolated groups. Reports of sexual transmission of HIV among non-IDUs are increasing. This is a warning sign that HIV is circulating in the general population.
In spite of the slow overall response Russian scientists have gained some support for AIDS vaccine research. At present three groups have small government grants to develop vaccine candidates. US and UK governments and academic institutions are also providing support for vaccine research and related activities including studies of who is infected, how rapidly HIV is spreading in different communities, how people are becoming infected (routes of transmission, see Primer), and what ‘clades’ (types) of HIV are found in Russia.
The first incidence study in Russian IDUs is currently underway at the “8 Plus Clinic” at the Biomedical Center in St Petersburg. The study is co-funded by the US HIV Prevention Trials Network (HPTN). It has enrolled 520 HIVnegative IDUs who will be followed for 12 months and tested for HIV every six months. Half-way through the trial more than 80% of the original volunteers are still enrolled. This is a strong start for this type of research. Biomedical Center head Andrei Koslov hopes the current study will help prepare the IDU community for future vaccine trials.
The study at the 8 Plus Clinic is helping to challenge stereotypes about IDUs, who are often seen as difficult to recruit and retain in studies. With the exception of Thailand, most countries with serious HIV epidemics in IDUs have failed to study or work with these communities.
If Russia is able to build IDU cohorts (groups of volunteers for studies) it will be a valuable contribution to AIDS vaccine research. It is important to include IDUs in trials to learn whether vaccines offer similar protection against both intravenous and sexual exposure to HIV (see Primer). Since sexual transmission is now increasing in Russia, the country could be an important site for trials that compare vaccine effects in IDUs and people exposed through sexual contact.
International partners are also hoping to strengthen Russian vaccine manufacturing capacity. One project aims to convert former bioweapons facilities to medicine and vaccine production. “When an AIDS vaccine is finally licensed, Russia could play a key role in manufacturing for many parts of the world,” says Don Burke, head of the Center for Immunization Research at Johns Hopkins University.
Obstacles to progress
Sadly, projects like the 8 Plus Clinic remain rare in Russia. In 2002 the government budget for AIDS spending was just US$ 5.5 million. In contrast, the US spends roughly $15 billion per year on domestic HIV/AIDS programs.
Stigma and discrimination also remain major problems. Active IDUs are ineligible for most health care including HIV treatment. Russian law requires that people with HIV are registered by name with the national authorities. This requirement may stop some people from seeking HIV testing. (At the 8 Plus Clinic each volunteer is assigned a numerical code. Staff doctors never learn their patients’ names and so avoid the requirement of reporting volunteers’ HIV test results to the authorities.) The government also does not support prevention strategies such as syringe exchange and drug replacement programs that provide a substitute to illegal intravenous drugs.
The handful of initiatives that do exist cannot solve the problem alone but they are a sign of what is possible in Russia should the government choose to respond. In a promising step the Russian government recently launched an AIDS advisory council that could coordinate a national research agenda.
This progress should have been made much earlier, Russian scientists say. “Recently we attended parliamentary hearings where the Russian authorities all started their speeches by saying, ‘Attention, attention, we are on the edge of disaster. Our house is on fire,’” says Eduard Karamov, a researcher at Moscow’s Ivanovski Institute for Virology. “I said, ‘Calm down, sit back, the fire started many years ago.’”
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All articles written by Emily Bass