“We were all pretty sad sacks, after seeing all these vaccine trials and not really seeing anything,” Dr. Mary Marovich said early last week, reflecting on the state of the HIV vaccine research field just a few years ago. Marovich, of the National Institute of Allergy and Infectious Diseases, was emphasizing the contrast between then and now.
Those few years since trials of a Merck HIV vaccine candidate showed slightly higher rates of infection among those taking the product over those taking the placebo, while other trials had shown no difference at all, have been superseded by a series of discoveries on the shape of the virus itself, on antibodies that can have the broadly neutralizing effect needed to attack the virus’s shifting forms, on responses from the immune cell the virus attacks, the possibility that an approach that is clearing a simian version of HIV from monkeys could lead to a therapeutic vaccine resembling a cure for humans, and, still most encouragingly, on the trial of the RV 144 HIV vaccine regimen in Thailand, the one trial to yield results of a regimen showing effectiveness against the virus.
All of these developments have years of research and testing ahead of them at best before they can lead to a vaccine against HIV that can be used, and realize the long-hoped for dream of permanently turning the epidemic back. For none of these advances, in fact, will any responsible researcher project a time when that might be the case.
At this first international meeting to bring researchers from all biomedical HIV prevention approaches together under one roof, neither the time and disappointments leading up to this point, or the uncertainty of how much more time lies ahead, did anything to dampen a sense of optimism and ambition that AVAC director Mitchell Warren sums up as “momentum.”
It is a momentum that comes not just from the advances in HIV vaccine science, but a gathering force of advances across the HIV biomedical prevention field that includes progress in topically applied microbicides to protect individuals from HIV infection, prophylactic use of antiretroviral treatment — PrEP to protect uninfected individuals, and treatment of infected individuals as prevention of HIV transmission. The potential for the sum of those advances to be greater than their individual impacts has driven an optimism that has researchers talking about which preventive product might be used by who, and in what combination with other prevention products, most of which do not exist yet for distribution, all of which face obstacles in the resource poor, heavily HIV burdened environments where they are needed most.
At the same time, a heightened circumspection about what is not known about both the needs and challenges of many of the people for whom making these products available and usable will be most critical, and about what additional surprises science might still spring drove the content of much of the conference.
Much of this circumspection stems from VOICE, a three-country, multi-site randomized clinical trial to test the potential effectiveness of Vaginal and Oral Interventions to Control the Epidemic, which revealed that while some of the products might have been successful if used, many of the women, particularly the young, unmarried women whose need for such products has driven researchers, did not use the products enough to prove they worked. But this humbling news had also followed the FEM-PrEP trial of oral pre-exposure antiretroviral medicine to prevent infection, which as researchers put it at the time “reinforced the key role of adherence,” because too few participants actually took the product. It also followed the MDP 301 trial of a microbicide gel which was not effective, but more importantly, as the disappointing results led, in Mazabuka, Zambia to misreporting and widespread suspicion of the product and the trial, revealed a massive failure on the part of researchers to communicate with community leaders, journalists, and by many indications, the participants themselves.
Conference co-chair and Microbicide researcher Sharon Hillier called the revelations of the VOICE trial a “life-changing experience” that “has changed the way we do business.” In fact, she and others point out that the very concept of “adherence” has been held up for re-evaluation. “I think we misjudged whether of not these products were going to fit into the lives of these young people,” she reflected. This, in turn, fuels hopes that two trials of antiretroviral-containing silicone rings to be worn in the vagina for 30 days or more will meet those needs. In addition, even while a proven useful delivery system of a reliable topical HIV prevention method still lies ahead, the possibilities of rings or other technologies that can prevent other sexually transmitted infections and unintended pregnancies along with HIV were the topic of talks and sessions throughout the conference.
It is a different era from that when what was thought to be impossible, improbable or impractical dominated discourse surrounding the epidemic. At the same time, themes of good participatory practices and community involvement throughout the conference, seemed to replace an old confidence that scientific soundness on its own could end the epidemic.
That turn, from what Glenda Gray, president of the South Africa Medical Research Council called “all breakthrough, no follow through,” made the view of a day when HIV is controlled, by science, by governments, by communities and by individuals clearer if still distant.
Obstacles yet unanticipated could still slow the way there. While the Ring and ASPIRE trials with the potential for a long term rather than daily prevention product they offer, answer one of the challenges raised by VOICE trial participants, the trials started before the still emerging feedback from the VOICE trial emerged. And when asked if the VOICE trial raised concerns about communication with participants in The Ring and ASPIRE studies, Zeda Rosenberg, chief executive officer of product developer International Partnership for Microbicides, did not answer.
Some answers from those trials will be on the way by the time the next HIV R4P conference meets in Chicago, Illinois in 2016. That’s also when answers of where the optimism and ambition of this conference is leading, will be clearer too. “It will be real,” Warren said, “if we actually act differently after Cape Town.”