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The Lancet/Cell Conference Asks: What Will it Take to Achieve an AIDS-free World?

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"What will it take to achieve and AIDS-free world?" was the question on everyone's mind at a small meeting of the same name held November 3-5 at the St. Francis Hotel in San Francisco. A Cell press release stated that the goal of the meeting was to "bridge the gap between researchers and clinicians in a joint effort to identify what needs to be done before an AIDS-free world can go from dream to reality."

The translational medicine conference, organized and sponsored by The Lancet and Cell medical journals, brought together over 200 leading HIV research and clinical practice experts from 6 continents.

Richard Horton, editor-in-chief of The Lancet, opened the meeting with a compelling question about the possibility of a cure, asking whether it would cause complacency. He pointed out that the best we can ultimately hope for is "low endemic levels of HIV." He added that besides the research questions, there are enormous political, economic, and structural forces that will press the questions about maintaining funding and neglecting key populations and geographies. In the end, these issues became the underlying theme of the meeting, where there was otherwise little new data.  

 

 

"It’s much too soon for a victory lap," claimed Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases, in his opening review of scientific advances, but he spoke of a shift towards translation and implementation of recent findings.

In terms of prevention, Fauci said that we have not yet reached the goal of a 33% reduction in HIV infections and have much work to do, especially in the areas of expansion of testing and male circumcision. He spoke of the fact that HIV vaccine research has seen years of disappointment, but this past October there were many papers published on new vaccine discoveries.

With regard to the 35.3 million people currently living with HIV, Fauci discussed optimization of treatment and the need for more potent, less toxic, and longer acting drugs for antiretroviral therapy (ART). As far as a cure for HIV, he stated that researchers must extrapolate from what has been learned with the various cure cases thus far, but concurred that the most practical approach would be to move forward with efforts to achieve "sustained remission" after early treatment, as seen in the VISCONTI Cohort and the Mississippi baby cure case. Finally, Fauci reiterated that a cure would need to be safe, administered with no tertiary care needed, and most definitely scalable.

The meeting's first session consisted mostly of basic science review talks on targeting HIV reservoirs and other cure-related research. Robert Siliciano of Johns Hopkins spoke about the recent research published in CELL that found that the size of the latent reservoir is 60 times larger than previously thought.

Romas Geleziunas, lead researcher at Gilead Sciences working on eradication therapies, described new work on a specific neutralizing antibody known as PGT121; with the Gates Foundation he will be moving forward in studying this approach in monkeys. Gilead has other work ongoing on several approaches for reservoir reduction such as TRL-7 agonists and the use of combination therapies, which almost everyone regards as the way forward for any cure strategy.

Warner Greene from the Gladstone Institutes in San Francisco spoke about his studies that for the first time mechanistically link 2 HIV pathogenic signatures commonly mentioned in eradication work, inflammation and CD4 T-cell depletion. According to Greene, such discoveries could lead to "an affordable bridge therapy for 16 million people who currently need but do not have access to ART, a potential solution for those on ART who are developing aging-related diseases a decade or more before the non-infected population, and a potential clearing of the latent reservoir that could contribute to a cure for HIV/AIDS."

HIV vaccines were a recurrent thread throughout the meeting, with a session dedicated to "Vaccines and Harnessing the Immune Response." Despite already having moved the goalpost for a successful vaccine forward 10 years, it will likely be moved yet another 10 years into the future. While there have been many setbacks and disappointments, a lot has also been learned. The central discussion concerned recent advances in broadly neutralizing antibody research by Gary Nabel, Dennis Burton, and Michel Nussenzweig. The trajectory seems to be looking at the kinds of antibodies people make in response to long term HIV infection. David Baltimore from the California Institute of Technology stated in his talk, "We need a vaccine, but we still don't have an open road in front of us."

Any discussion of ending AIDS must address prevention, and indeed the conference included a session on "Antiretrovirals for Primary and Secondary HIV Prevention." An examination of ending AIDS throuh global access to antiretrovirals was the focus of a talk by Wafaa El-Sadr from Columbia University. She spoke of the need for a roadmap for ART scale-up in diverse settings, emphasizing that "it is critical to achieving optimal outcomes for both people living with HIV and for prevention."

The "AIDS-free generation" sound-bite has been perceived as insulting by many people currently living with HIV. The organizers adeptly addressed the issue with a session on co-morbidities and aging, opened by long-time AIDS researcher Jay Levy from the University of California at San Francisco (UCSF), dedicated to the issues of people who have been living and surviving with HIV/AIDS for decades.

"By definition AIDS is a syndrome of complications associated with advanced immunodeficiency," stated Steve Deeks, also from UCSF. "If we can get everyone on [antiretroviral] therapy, then AIDS will essentially be gone." He stressed that understanding the links between HIV, ART, and aging will be critical to healthy and thriving older age in people with HIV. Community members allowed entry to the conference as press stressed the necessity of research into mental health issues, especially for long-term survivors.

In a dinner keynote address, the "Berlin Patient," Timothy Brown, spoke to conference delegates about his experiences as the first known person to be cured of HIV. Paula Cannon, a stem cell researcher from the University of Southern California, said of his talk, "I have heard Tim speak several times now, but the simple power of his message remains just as strong as ever. We are lucky to have such a sincere, humble, and generous individual as an ambassador for this effort."

The meeting ended on a somewhat positive note with a panel discussion by several local and global leaders in the quest for an end to AIDS. Nobel Laureate Francoise Barre-Sinoussi spoke about the ongoing work of the International AIDS Society and the growing interest in finding a cure. "I'm here as a witness of 30 years of science and translational research," she exclaimed. "We need to continue the effort of working together if we want to make progress toward a cure."

David Evans, a community advisory board member for the Delaney AIDS Research Enterprise and Director of Research Advocacy at Project Inform, said of the conference, "A case was well made for the potential of cure research and what might be able to be achieved with HIV treatment as prevention. What was lacking, however, was both the science and advocacy on the role that people living with HIV can play as equal partners in ending the epidemic."

To that end, an interesting discussion will continue on the complexities and challenges the global community will need to address before an end to AIDS is ever achieved.

11/15/13

Source

What Will it Take to Achieve an AIDS-free World? The Lancet/Cell Translational Medicine Conference on HIV Research. San Francisco. November 3-5, 2013.