PxWire is AVAC’s quarterly update covering the latest in the field of biomedical HIV prevention research, implementation and advocacy. Highlights in this issue include: next steps in AIDS vaccine trials in the post-Thai vaccine trial (RV144) era; “test and treat” approach for prevention presented at CROI; a preview of AVAC Report 2010; information on the Microbicides 2010 Pre-Conference Advocacy Workshop; new funding for advocacy related to MSM and prevention research; six new clinical trials looking at enhanced prevention strategies.
Px Wire April-June 2010, Vol. 3, No. 2
Px Wire January-March 2010, Vol. 3, No. 1
PxWire is AVAC’s quarterly update covering the latest in the field of biomedical HIV prevention research, implementation and advocacy. Highlights in this issue of PxWire include updates on: the results from MDP 301, a trial of the microbicide PRO 2000, which lay to rest its prospect as a viable microbicide; CDC’s newly modified PrEP trial (TDF2 in Botswana), which changed its status as an efficacy trial to a safety and behavioral study; the evolving effort to understand the Thai prime-boost AIDS vaccine results; recent NIH grants that nearly double global spending on rectal microbicides; and a timeline of 2010 trial milestones—what trial results are expected and what new studies are scheduled to commence?
Press Release
AVAC Praises Thai AIDS Vaccine Trial Collaborators and Volunteers for Historic Study
New York, NY, September 24, 2009 , “Today marks an historic milestone in the search for an AIDS vaccine; we now have evidence that it is possible to reduce the risk HIV infection with a vaccine,” said AVAC executive director Mitchell Warren, reacting to the results of the first AIDS vaccine trial to ever show efficacy at preventing HIV. “It will take time and resources to fully analyze, understand and validate the data, but there is little doubt that this finding will energize and redirect the AIDS vaccine field as all of us begin the hard work to translate this landmark result into true public health benefit.”
“We congratulate the trial sponsors, scientific collaborators and partners who conducted this trial, and especially want to thank the more than 16,400 Thai men and women whose altruism and commitment as trial volunteers made this effort possible. These volunteers and their communities have made an inestimable contribution to HIV prevention research. We all owe them a debt of gratitude,” Warren said. “As we move forward in our search for vaccines and other new HIV prevention interventions, researchers will need the collaboration of tens of thousands more volunteers around the world in additional trials. We are confident that many more communities and individuals will follow in their footsteps.”
As the trial team reported in Bangkok today, the Thai prime-boost trial found that rates of HIV infection were roughly 30 percent lower among volunteers who received the vaccine versus those who received the placebo. This is the first evidence of an AIDS vaccine providing any level of protection against HIV infection. Statistical analyses presented as part of this initial announcement support the validity of the finding. It is important to remember that the trial was a “test of concept” study designed to identify initial signs of promise in a product. The trial sponsors and implementers, led by the US Military HIV Research Program and funded by the National Institutes of Allergy and Infectious Diseases (NIAID), have been clear that additional studies would be needed to further understand any positive result. There is now an imperative on the trial team and the field as a whole to determine what those steps will be and to implement them with all due haste. Additional analysis of the trial data are expected to be presented at the annual AIDS vaccine meeting that will take place in October.
The trial looked at vaccine impact on risk of infection and on viral load among vaccine and placebo recipients who received the vaccine and went on to acquire HIV. The vaccines themselves are not capable of causing infection. There was no evidence of an impact on viral load, a goal that has been embraced by many vaccine stakeholders as more realistic and attainable than an impact on risk of infection.
“These results move us one step further along in the marathon journey of AIDS vaccine research that continues. They also demonstrate that the scientific process is remarkable and unpredictable, and underscores the need for testing strategies in human efficacy trials. We look forward to more data from the trial in the coming weeks that will help guide the decisions about the design of additional trials of this strategy, and the impact of this finding on broader AIDS vaccine research,” Warren said.
“AVAC calls on the trial sponsors, vaccine manufacturers, researchers, funders and others in the field to work quickly, cooperatively and boldly to translate these results into development of a scientific action plan, a plan for community engagement in Thailand and around the world, and a broader communication effort to convey both the promise and limitations of this result. Above all, we must ensure that all stakeholders, including private industry, which played a critical role in this trial, reaffirm their commitments to work that will lead to eventual access to an effective vaccine for people around the world, ” Warren said.
The trial team and Thai collaborators held extensive consultations to determine next steps in various scenarios and determined that a vaccine effect of 50% or higher would trigger a licensure application in Thailand. This finding does not reach this threshold. The same consultations determined that a modest effect, such as was reported today, would trigger additional discussions about the way forward. These new consultations are an essential next step and should include a range of stakeholders including members of communities that might use such a vaccine.
Stakeholders within Thailand and around the world must recognize and rise to the challenge of explaining the promise of this proof of concept as well as the rationale for proceeding with a thorough consultative process and data analysis before making any decisions about future access.
It is important to note that the two vaccines tested in the Thai trial contain synthetic fragments of subtype E, one of the most common HIV strains circulating in Thailand and Southeast Asia. The regimen also contains subtype B, which is most common in North America and Europe. Therefore this result estimates the level of protection conferred by a vaccine that includes genetic fragments matched to the common circulating subtype. Scientists do not know whether a vaccine that is effective against the strains that are found in a given geographical area will also be effective in other areas and against other strains of HIV. The trial collaborators and other experts are already planning follow-up studies to confirm and elaborate on this and other findings from this trial.
“This is an astonishing scientific achievement, well beyond the expectations of many scientists. It starts a new chapter in the search for an HIV vaccine: to make highly protective vaccines that can be made available to all who need them. There is a great deal of work to be done on many fronts at once, and AVAC is fully committed to hastening that day. We need to enlist a larger number of new vaccine advocates to keep the process moving productively as quickly as feasible,” said Bill Snow, an AIDS vaccine activist since 1991, and a co-founder of AVAC in 1995.
There are also still other HIV vaccine strategies in laboratory and human testing. Furthermore, other HIV prevention options, particularly microbicides and pre-exposure prophylaxis, or PrEP, are being tested in efficacy trials which will yield results in the next few years. In the last few years, clinical trials have also shown that medical male circumcision can be effective at reducing the risk of HIV infection in heterosexual men.
“This step adds immensely to the drive for comprehensive HIV prevention,” Warren added. “That means perfecting methods and ensuring access for all who need it to existing HIV prevention and treatment options, including male and female condoms, behavior change counseling, male circumcision, clean needles, harm reduction and antiretroviral drugs; ensuring continued research to find effective new options, including vaccines, microbicides, and PrEP; and planning for integrating these new interventions into combination programs.”
More information about the Thai trial results is available on the AVAC website at http://www.avac.org/thaitrial.htm. Additional information will be added as it becomes available.
Contact: Mitchell Warren, +1 (914) 661-1536, [email protected]; Kay Marshall, +1 (347) 249-6375
Anticipating the Results of the Phase III AIDS Vaccine Trial in Thailand
A 2009 document discussing the RV144 vaccine trial in advance of efficacy data. It provides background information on the vaccine candidate and trial design, and explores potential scenarios for the results.
Press Release
Shifting Scientific, Health Priorities and Global Economic Downturn Impact Investment in HIV Prevention R&D
Cape Town — A new report on investment in HIV prevention research in 2008 finds that HIV vaccine research funding levels decreased for the first time since investment trends have been tracked. This may have been influenced by shifts in scientific priorities, the declining economy and competing priorities in the larger global health agenda. Despite this decrease, the overall trend since 2000 has been of increasing investment for experimental biomedical prevention strategies.
The report, Adapting to Realities: Trends in HIV Prevention Research Funding 2000 to 2008, was released at the 5th International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention in Cape Town South Africa by the HIV Vaccine and Microbicide Resource Tracking Working Group. It is available online at http://hivresourcetracking.org/.
The report identified investments of almost $1.2 billion in HIV prevention research in 2008, of which $868 million supported vaccine R&D, and $244 million supported microbicide R&D, while other HIV prevention R&D received much lower levels of funding. AIDS vaccine research declined for the first time since 2000, falling by ten percent from 2007 levels. At the same time, funding for both microbicides and preexposure prophylaxis (PrEP) increased by eight and 13 percent, respectively.
Funding for HIV prevention research remains a relatively small percentage of the overall response to HIV/AIDS. A recent report released by the Kaiser Family Foundation and UNAIDS documented commitments from the developed world for HIV/AIDS treatment and prevention programs in developing countries of $8.7 billion in 2008, up from $6.6 billion the previous year.
“Research to develop new HIV prevention tools and strategies is essential to prevent new infections, and an HIV vaccine still holds the greatest hope to ending the epidemic,” said Michel Sidib�, Executive Director of UNAIDS “It is vitally important that investments into research for HIV prevention be sustained and increased for as long as it takes to reach those goals.”
The Resource Tracking Working Group identified a critical need in this time of shifting budget priorities and economic uncertainty for the HIV prevention research field to identify funding needs and put in place scientific plans to help guide research decisions. These steps will ensure that there is no duplication of efforts and that funding can be linked efficiently to scientific priorities.
“Support and interest in HIV prevention research from public, private and philanthropic funders over the last decade has supported key R&D priorities, moved the field forward and brought us closer to new HIV prevention options,” said Mitchell Warren, executive director of AVAC. “We face tremendous challenges — both scientific and economic — over the coming years, but we must not lose the momentum we have gained. The field needs sustained support from a range of funders. The AIDS epidemic shows no signs of slowing, and the desperate need for new HIV prevention options will not change.”
Levels of funding in 2008 reflected key shifts in the HIV prevention research field. The halting in late 2007 of the Step and Phambili vaccine trials, which were testing a candidate vaccine developed by Merck, ended one of the only pharmaceutical company partnerships for HIV vaccine R&D. This slowing in industry involvement is reflected by a decline in industry funding levels in 2008. Pharmaceuticals and biotech companies in 2008 accounted for only four percent of HIV vaccine research funding. Levels were even lower across other HIV prevention research priorities. Nevertheless, the commercial sector contributes to the development of HIV prevention research in a number of ways through pharmaceutical company support. A number of companies have provided ARV compounds for development as potential microbicides, and as oral PrEP, along with technical support to microbicide product developers.
“The worldwide economic crisis has fueled debate about the best way to invest in global health, with some arguing that AIDS takes up resources at the expense of efforts to deal with other diseases and to improve health systems in the developing world. But given that AIDS is the number one killer in sub-Saharan Africa, and number four in the world, it is imperative that we reverse this pandemic, and that can only be done through improved methods of prevention, including a vaccine. If we can conquer AIDS, we will be able to invest resources in other pressing priorities,” said Seth Berkley, President and CEO of the International AIDS Vaccine Initiative.
It is important to note that HIV vaccine research and development is continuing to move forward. Just today, the South African AIDS Vaccine Initiative announced the start of a trial to study a vaccine candidate developed by local South African scientists. Results are also expected later this year from the largest vaccine trial ever, which successfully enrolled more than 16,000 participants. In addition, researchers around the world are developing new vaccine approaches and conducting basic research to inform vaccine development.
The report notes that increased investment in microbicide R&D may reflect increased interest in research on antiretroviral (ARV)-based candidates. Investment increased in microbicides overall at the same time that the field intensified its focus on ARV-based approaches to microbicide development.
“Increased funding for microbicide R&D over the past decade has fostered a major expansion for the field; clinical trials of microbicide candidates have been conducted in 27 countries around the world; and pre-clinical research has yielded important scientific information. Support from public, private and philanthropic funders is essential to increase R&D for new microbicide candidates,” said Polly Harrison, Director of the Alliance for Microbicide Development.
The U.S. government was once again the primary funder for HIV prevention research, supporting 71 percent of HIV vaccine R&D, 63 percent of microbicide R&D, and providing 46 percent of funding for PrEP prevention research in 2008. A decrease in investment from the U.S. National Institutes of Health contributed to the overall decline of funding for HIV vaccine R&D. The U.S. government investment fell by $39 million, a six percent decrease. Other governments also decreased funding for HIV vaccine research in 2008: European government funding fell by 13 percent and total funding from other countries (including Brazil, Canada, India, South Africa, and Thailand) fell by 16 percent.
The report authors caution that while it is too early to attribute all of the funding decreases to the financial crisis, there is concern that a prolonged global recession could have a major impact on public investment in all HIV/AIDS programs. A recent report from UNAIDS and the World Bank found that the economic crisis has already affected levels of funding for treatment and prevention programs in some developing countries.
The Working Group also reported on investment in operational research related to proven biomedical HIV prevention research interventions — medical male circumcision and ARVs for prevention of vertical transmission of HIV from mother to child. These efforts are being funded at much lower levels that other HIV prevention research, with $11 million supporting research related to rollout of male circumcision and $21 million supporting operations research for prevention of vertical transmission.
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Press Release
Piecing Together the HIV Prevention Puzzle: AVAC Report Assesses Progress in AIDS Vaccine, Microbicide and PrEP Research and Calls for Urgent Coordination and Leadership in Advance of Upcoming Results
New York, NY — “It’s an exciting time in HIV prevention research. We will see results from a number of critically important HIV prevention research trials this year, as well as see the start of new trials around the world that will yield important answers in the years to come,” said Mitchell Warren, AVAC executive director, at the release of AVAC’s 13th annual report of the field.
“But scientific, community and political leaders must act now to plan for continued research and implementation of effective strategies, or this excitement will be wasted.”
The report — Piecing Together the HIV Prevention Puzzle — looks at AIDS vaccine research, where there is an energized focus on discovery, innovation and basic science and looks at the broader HIV prevention field, particularly the implications of pre-exposure prophylaxis (PrEP) and other strategies in efficacy trials today.
This analysis of the HIV prevention field comes in a year that has already brought disappointment as well as intriguing results from various prevention studies. At the same time, even trials that failed to show overall benefit, such as the Step Study of the Merck HIV vaccine candidate, have continued to generate new, valuable information and questions that would not otherwise exist.
These trials have succeeded as a result of increasingly robust partnerships between researchers and communities grappling with HIV, including gay men around the world and heterosexual women in Africa. These partnerships, along with the persistently high rates of new infections, are a continual reminder of the global commitment to and need for continuing the search for new prevention for as long as it takes.
“We hope to have new prevention intervention pieces to add to the puzzle in the next few years,” said Warren. “But as the slow implementation of male circumcision to reduce heterosexual men’s risk of HIV infection reminds us, we need extensive planning and guidance to ensure research results are translated into real impact against the epidemic. We can’t afford to wait for efficacy results before we begin to plan. We must anticipate and tackle the major hurdles for implementation now.”
The Report identifies major issues for implementation of new prevention options, including:
– Ongoing global failures to scale up access to HIV testing and counseling services.
– Persistent inattention to the needs of gay men and other men who have sex with men around the world.
– Gaps in health care infrastructure that will complicate introduction of any new strategy.
In the Report, AVAC also underscores the importance of WHO and UNAIDS getting involved in planning for the results from PrEP trials before data are available.
“WHO and UNAIDS, along with other stakeholders, need to combine their strengths now to provide leadership and coordination so that the world is ready to work with results from the many ongoing PrEP trials,” said Warren.
Positive results from current vaccine, PrEP and microbicide trials will also present challenges and opportunities for other ongoing and planned HIV prevention trials.
“There has been concern that positive results from PrEP trials would require vaccine or microbicide trials to become larger, longer and more expensive, as PrEP could become a standard of prevention in these trials,” said Warren. “But we believe that success in one trial will open up possibilities and options for research that could combine AIDS vaccines and other interventions as they emerge.”
To help guide efforts in new areas of research and sustain ongoing research, AVAC calls for researchers and trial sponsors to begin planning on how combination strategies can be evaluated.
As the field looks to fit the puzzle pieces together, the AVAC Report also identifies a number of big questions in AIDS vaccine research for 2009 and beyond, focusing on issues such as cell-mediated viral control, HIV genetic diversity, the role of animal models, immune activation, antibodies and adjuvants.
In its analysis of the vaccine field, AVAC also assesses the progress and future potential of the Global HIV Vaccine Enterprise and considers the impact of results from the Thai prime-boost vaccine trial that are expected in September. With over 16,400 participants, this is the largest AIDS vaccine trial ever undertaken.
“In AIDS vaccine and HIV prevention research today, we see a fertile mix of big science and individual efforts, of product-oriented work and of slow and steady basic science,” Warren added.
“What we need now is a quick, strategic, scientific analysis of all the efforts underway, with a goal of identifying gaps and opportunities for synergy both within the AIDS vaccine field and across the vaccine, PrEP, and microbicide fields. AVAC is excited to help move the HIV prevention field toward a collaborative agenda and to prepare now for implementing potential new prevention options.”
Piecing Together the HIV Prevention Puzzle is available at http://www.avac.org/reports.htm.
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Px Wire January-March 2009, Vol. 2, No. 1
PxWire is AVAC’s quarterly update covering the latest in the field of biomedical HIV prevention research, implementation and advocacy. Highlights in this issue of PxWire include a report on data from the Step vaccine trial and animal studies of relevance to the proposed HVTN 505 trial of the NIH Vaccine Research Center DNA-Ad5 combination strategy presented at the Keystone Symposium on HIV prevention–an annual meeting focused on basic and preclinical science. This issue also reviews newly launched trials, lays out this year’s upcoming trial milestones, and gives information on ordering the 2009 AVAC report on the prevention research field, to be released in May.
Px Wire October-December 2008, Vol. 1, No. 4
Px Wire is AVAC’s quarterly update covering the latest in the field of biomedical HIV prevention research, implementation and advocacy. Highlights of this year-end issue include: AVAC’s take on the year in prevention research; an update on the proposed AIDS vaccine trial HVTN 505; news on the female condom and microbicide trials.
Px Wire July-September 2008, Vol. 1, No. 3
PxWire is AVAC’s quarterly update covering the latest in the field of biomedical HIV prevention research, implementation and advocacy. Highlights in this issue of PxWire include a discussion of the no-go decision on the proposed PAVE 100 vaccine trial (though the candidate may yet be tested), updates on women’s input into male circumcision for HIV prevention, and AVAC’s take on indelible moments and themes from the International AIDS Conference in Mexico City in August.
Press Release
Immunizing Against Misinformation and Shortsightedness: AVAC Report Injects a Dose of Reality into the Debate on the State of AIDS Vaccine Research
New York, NY , The AIDS Vaccine Advocacy Coalition (AVAC) today released a new report that provides a comprehensive review of recent developments in AIDS vaccine research. AVAC Report 2008: The Search Must Continue explores the issues that have been raised in the wake of the failure of Merck’s vaccine candidate and provides context for the events and major changes of the last year in HIV prevention research.
In the Report’s opening letter, AVAC Executive Director Mitchell Warren says “Enough is enough,” with regard to the misinformation that has crept into some of the public conversations about AIDS vaccine research. In the report, AVAC argues that continuing to move forward with AIDS vaccine research and testing is imperative and lays out recommendations for the AIDS vaccine and HIV prevention field.
AVAC’s 11th annual Report on AIDS vaccines also looks at the comparative advantages of major players, including the U.S. National Institutes of Health and the International AIDS Vaccine Initiative, and analyzes the current environment for decision-making about future clinical trials. The report is available online at www.avac.org/reports.htm.
The AVAC Report comes at a critical time for HIV prevention research. Over the past 12 months, several trials, including vaccine, microbicide, cervical barrier method and herpes-treatment trials, have yielded disappointing results of no efficacy. Recently, a slew of editorials and media coverage have spotlighted AIDS vaccine research and, in some instances, included calls to end public funding or to reapportion funding away from AIDS vaccine research toward existing HIV treatment or prevention interventions. At the same time, there are ongoing discussions at the NIH about whether to launch another vaccine efficacy trial using a strategy developed by the NIH’s Vaccine Research Center.
“With recent pessimistic headlines and the creation of na�ve and false dichotomies between research and clinical trials or between treatment and prevention or existing interventions and new research, we at AVAC say enough is enough,” said Mitchell Warren, executive director of AVAC. “An AIDS vaccine is possible, and it is essential.”
“It’s been a challenging year for the AIDS vaccine field and for HIV prevention research generally, but the recent spate of statements that seem to revise the history of the past few years of AIDS vaccine research are deeply troubling,” said Warren. “Now more than ever, we must maintain momentum in AIDS vaccine and other HIV prevention research while simultaneously continuing to ramp up provision of existing treatment and prevention options for all those who need them.”
“We were all disappointed with the results from the trials of Merck’s vaccine candidate last year,” said Pontiano Kaleebu, Assistant Director of the Uganda Virus Research Institute, Chairperson of the African AIDS Vaccine Programme, and an AVAC board member. “But we must now reclaim the narrative of what happened with trials of that vaccine and of what they mean for the future of AIDS vaccines and HIV prevention. Here in Uganda and throughout Africa and the world, we still desperately need an AIDS vaccine and we are committed to continuing the search.”
“There have been major changes in the AIDS vaccine field and in biomedical HIV prevention research in the last year. The AVAC Report provides a comprehensive and sensible guide to where the vaccine field stands now and where it needs to go,” said Alan Bernstein, executive director of the Global HIV Vaccine Enterprise.
In The Search Must Continue, AVAC makes several key recommendations for moving the AIDS vaccine and HIV prevention research fields forward, based on a comprehensive review of recent events in the field and future plans of the major players in AIDS vaccine and HIV prevention research as well as conversations with researchers, funders, policy makers and community representatives. These recommendations include:
Ensure that the scientific data from the STEP trial are fully assessed and used to inform the design of improved immunization strategies.
Articulate the human discovery trials agenda and balance vaccine discovery and development.
Structure the vaccine field so that there are career paths for young investigators.
Prepare for results of the Thai prime-boost vaccine efficacy trial.
Systematically improve community engagement strategies, especially as decisions are made around the design of the PAVE 100 vaccine trial.
Clearly communicate and manage expectations of prevention research trials and results.
Increase support for pre-exposure prophylaxis (PrEP) research as well as community stewardship of this promising area of research.
Engage in meaningful dialogue around the scaling-up of male circumcision programs that adequately address HIV testing and gender-specific issues in program rollout.
Expand community engagement with and critique of the microbicides science agenda.
Reconsider how clinical trials infrastructure is sustained and clinical research agendas are developed, in discussion led by developing country voices.
The Report is being released ahead of HIV Vaccine Awareness Day, May 18th, which commemorates U.S. President Bill Clinton’s call for a concerted effort to develop an AIDS vaccine within a decade. Today, it is a global observance to recognize and thank the thousands of volunteers, community members, health professionals, researchers and scientists who are working together to find a safe and effective AIDS vaccine.
“Yes, we have all been surprised and disappointed in the results of the Merck vaccine candidate,” Warren said. “But that is the nature of the scientific process. To acknowledge failure of a candidate vaccine is in no way to concede overall defeat. We all now have a tremendous opportunity to learn from these setbacks and to be better for them, better, even, than we might have been without them. This year, as we commemorate HIV Vaccine Awareness Day, AVAC remains committed and cautiously optimistic.”
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About AVAC: Founded in 1995, the AIDS Vaccine Advocacy Coalition (AVAC) is a non-profit, community and consumer-based organization that uses public education, policy analysis, advocacy and community mobilization to accelerate the ethical development and global delivery of AIDS vaccines and other HIV prevention options. For more information, visit http://www.avac.org/.