This update reviews some highlights of AIDS vaccine research at the International AIDS Conference in Vienna and also discusses the energized focus on identifying a cure for HIV. It is the third and final review in our post-Vienna series; previous editions include updates on male circumcision and ARV-based prevention.
While our series focuses on biomedical prevention research, the conference was marked by its emphasis on human rights as the foundation for an effective AIDS response. No biomedical strategy, however effective, will have a lasting impact without concurrent action on stigma, criminalization, legal rights and evidence-based, human-rights focused approaches.
One essential resource for a rights-based approach to research is the Good Participatory Practice Guidelines (GPP) for biomedical HIV prevention trials. A revised edition of this document was released for public comment in Vienna. GPP is designed to provide guidance on stakeholder engagement for trial implementers throughout the research life cycle. The original version, published in 2007, was developed through a consultative process led by AVAC and UNAIDS. This revision reflects input from a range of stakeholders--and is open for public comment through October 31. To learn more, visit avac.org/gpp or www.unaids.org. To request printed copies email firstname.lastname@example.org or email@example.com. Please send your comments on the draft second edition to firstname.lastname@example.org or email@example.com.
This update focuses on a few of the sessions that provided broad overviews of the state of the AIDS vaccine field. Many related topics were addressed in more detail than is provided here. Richard Jefferys of the Treatment Action Group compiled a list of links to relevant sessions as well as a helpful primer on accessing PowerPoint presentations and other materials including webcasts and posters via the conference website.
Antibody Research: A long road and a "renaissance"
For the microbicide field, the Vienna meeting brought clear cause for celebration due to the results of CAPRISA 004. AIDS vaccine sessions, while noticeably more crowded than those held at the 2008 International AIDS Conference, had a more contemplative tone. On the one hand, scientists were able to point to recent developments including the evidence of modest protection from the RV144 vaccine efficacy trial of ALVAC plus AIDSVAX, and the discovery of potent, broadly neutralizing antibodies in the blood of HIV-positive individuals. (Data on the most recent of these discoveries, announced by scientists at the US National Institutes of Health Vaccine Research Center, seized headlines when published in Science the week before the conference.)
In the symposium, AIDS Vaccines: Quo Vadis, Seth Berkley of the International AIDS Vaccine Initiative, said the recent advances in identifying broadly neutralizing antibodies and solving the structures of their binding sites amounted to a "vaccine renaissance." It is important to note that scientists don't yet know how to design a vaccine to induce these antibodies--which were all found in HIV-positive individuals. Therefore, it may take years to transform these developments into vaccine candidates for clinical testing. Berkley described one proposal for an intermediate step: clinical trials in which HIV-negative individuals would receive infusions of these potent antibodies. This strategy is known as passive immunization. In this context, passive immunization would involve monoclonal antibodies (antibodies made by identical immune cells that are all clones of the same parent immune cell). Since the injected antibodies are not formed by the recipient's own immune system, levels would decline over the course of a few weeks and regular boosters would be required to maintain steady levels. This is one reason passive immunization isn't a feasible biomedical prevention intervention. However, such trial of this strategy could provide a proof of concept for antibody-mediated protection. This could help guide vaccine design and other potential antibody-based prevention approaches.
Mapping the Post-RV144 Vaccine Clinical Trial Landscape
The need to continue and expand the range of AIDS vaccine clinical trials was echoed throughout a number of sessions. At a satellite session, The Search for an HIV Vaccine: Where are we, where are we going, and how can we get there faster?, Alan Bernstein of the Global HIV Vaccine Enterprise presented The Road to Prevention, a preview of the updated Enterprise Scientific Strategic Plan. The fully revised Plan will be released at the AIDS Vaccine 2010 Conference in September.
In his presentation, Bernstein identified further unification of basic science, preclinical and clinical research as a top priority. He said that it was important that clinical research be viewed as an integral part of the vaccine discovery process and not simply its culmination. This recommendation first emerged in initial analyses of where the field should go next in the immediate aftermath of the 2007 release of data from the Step trial that showed the candidate MRK-Ad5 had no benefit and appeared to have increased risk of infection in some individuals.
In the same session, Merlin Robb of the US Military HIV Research Program described activities following the RV144 result and laid out a two-pronged proposal for further clinical trials. He called one prong a "regional vaccine strategy" in which a regimen based on the RV144 prime-boost combination could be evaluated in a Phase IIb study in MSM in Thailand and high-risk heterosexuals in South Africa. This could explore different aspects of the finding in ways that might bring that approach toward approval. He dubbed the other prong a "global vaccine strategy", which would involve pursuit of an array of novel candidates that would ideally provide multi-clade protection via potent cellular and humoral responses.
AVAC Report 2010: Turning the Page, released just prior to the conference, provides an in-depth discussion of the trial designs, trade-offs and resource needs for pursuing both RV144 follow-up and wholly new ideas. Pursuing the expanded array of trials suggested by RV144 and, in the microbicide field, by CAPRISA 004, will likely require additional resources. The recently released report from the HIV Vaccines and Microbicides Resource Tracking Working Group, for which AVAC is the secretariat, surveys the resource commitments and needs for the vaccine, microbicide, male circumcision and PrEP fields. It reports that, while AIDS vaccine funding held steady from 2008 to 2009, there is an urgent need for additional donors to bring resources to the search so that the field is able to follow up on the promising results and also explore new, innovative strategies.
An Ounce of Prevention and...Hope for a Cure
Also in Vienna, scientists shared increased energy and optimism around using current knowledge to explore the potential for developing a cure for HIV. This growing area of inquiry was the subject of a pre-conference meeting organized by HIV co-discoverer Françoise Barré-Sinoussi of the Pasteur Institute, and further discussion at related sessions on viral latency and persistence of HIV reservoirs.
In brief and very broad strokes, this agenda is framed around the goal of identifying strategies to either eliminate HIV from the body or to allow people to stop taking antiretrovirals while controlling the small amount of HIV that might be left in their bodies. This latter approach is known as a "functional cure" in that it wouldn't clear the body of all traces of the virus. Plenary speaker Anthony Fauci of the US National Institute for Allergy and Infectious Diseases gave an overview of what this approach might look like. Additionally, a review of research on this topic was published in the issue of Science magazine leading up to the Vienna conference. In it, the authors noted the potential utility of a therapeutic vaccine that induces effective HIV-specific immune responses may be one component of a functional cure. The authors said, "Similar to developing an HIV vaccine, obtaining long-term drug-free remissions for HIV-infected individuals should be defined as a top strategic priority, and proper incentives and programs should be put in place to recruit the broad and multidisciplinary scientific research community that will be indispensable to succeed in this endeavor." In the coming year, AVAC will continue tracking therapeutic vaccine research and resources devoted to it.
Although this concludes our Vienna-specific coverage, our ongoing work on CAPRISA 004, treatment as prevention, PrEP, vaccines and many other topics will expand on the issues raised at this meeting. We hope you'll keep us up-to-date on your own perspectives, questions and priorities.