A chart of clinical research trials seeking ways to control HIV transmission makes for an impressive display of tenacity, with interrupted trials, ongoing trials, trials that led to other trials, and new trials in their earliest stages. It includes trials of microbicides, vaccines, antiretroviral-drug-based approaches and all of that in different combinations. It includes heartening breakthroughs, surprises and disappointments, and it promises to stretch on for years to come.
Such a chart, titled “HIV Prevention Options Timeline” was part of AVAC director Mitchell Warren’s presentation at a Jhpiego-sponsored look at “The Present and the Future of HIV Prevention,” Thursday evening, an event that, as it turned out, gave an up-to-the-minute look at the status and application of science’s efforts to control the spread of HIV.
At the bottom, a recently placed red “X” — for “no effect” summed up the news announced earlier in the day that the HVTN 505 AIDS vaccine clinical trial, a trial that had been repeatedly adapted to build on information yielded by previous trials, had been stopped when an independent monitoring board determined the regimen under investigation did not work. In the years of planning and preparation for the trial, researchers had changed participant eligibility requirements to exclude men who were uncircumcised and had antibodies to a common cold virus, in response to data from a trial called off in 2007 showing men with those characteristics had acquired HIV in higher numbers when trying a regimen with a related formulation. The trial had adjusted its protocol with the news that pre-exposure preventive use of antiretroviral drugs was an effective means to prevent HIV acquisition for men who have sex with men, to make that option available to would-be participants. The trial had expanded its scope to include discovery if the regimen being tried could not only lessen the impact of HIV acquisition, but prevent it. But in the end, announced that day, the trial had shown the regimen didn’t work at all, with those given the regimen acquiring HIV at slightly higher (but statistically insignificantly higher) numbers, than those taking a placebo.
“It’s disappointing,” said Warren, but added that the news may be a dead end for one approach, but not for the search it was part of. “Now we need to re-orient and go in a different direction.”
In that way the news became part of the ongoing evolution of a response to the HIV epidemic that has gathered force in the last two decades through the promises and questions generated by science.
It is an evolution that has prevented millions of infections from occurring in the last decade, and made the use of an unprecedented commitment of money increasingly effective and efficient, said Dr. Caroline Ryan, Director of Technical Leadership of the Office of the Global AIDS Coordinator, who spoke at the event about the impact of science in the creation of a “Blueprint” to create an AIDS-free generation, from President’s Emergency Plan For AIDS Relief.
Gaps continue, and questions remain, she added. While some of the countries hit hardest by HIV are seeing the “tipping point” at which the numbers of those on treatment exceed the numbers newly infected, five countries continue to lag, with numbers of new infections remaining high, and in the case of Uganda, even increasing. The search for answers there, too, continues, she said.
“It is science that will underpin all of our efforts to achieve this goal,” she said.
As the search for scientific answers continues, so does the quest to apply those answers where they are needed most, said Dr. Chris Beyrer, director of Johns Hopkins Fogarty AIDS International Training and Research Program said. In a week during which the U.S. Supreme Court heard oral arguments in the case of the “anti-prostitution pledge” and following the arrest and imprisonment of a Zambian man for speaking to the rights of gay people and sex workers, the topic of his talk, too, explored the status of a work in progress. He spoke to the need to bring “combination prevention” strategies to those in circumstances that make them most vulnerable to acquiring HIV (once known as “MARPs” — most at-risk populations, now sometimes called “key populations,” and in plainer language, men who have sex with men, people who inject drugs, people involved in sex work, transgender people). But first Beyrer defined “combination prevention” as “The simultaneous and strategic use of different classes of prevention operating on different levels to respond to the needs of different communities and modes of transmission.”
Much of the data for what combinations work best in what circumstances came from modelling, rather than real life, Beyrer said, because the people most in need of prevention methods targeted to their situation are the ones least likely to get it. That includes people involved in sex work, who are 14 times more likely to get HIV than others in their settings, and transgender women, the most disproportionately affected of all, with 50 times the likelihood of getting HIV.
The evening also included news of the rapid advances in acceptability of and access to medical circumcision of men to prevent HIV, by Tigistu Adamu of Jhpiego, and a reminder of what “prevention of mother to child transmission” includes, by Rene Ekpini of UNICEF, whose presentation included a depiction of the “four-pronged approach,” to that goal, which includes working with women to help keep them from getting HIV, responding to their family planning needs to prevent unintended pregancies, as well as treatment, and care for infants.
Here too, the story of the most successful prevention effort so far was updated by recent events, even if, as Ekpini noted, their ramifications are yet to be confirmed. To his chart depicting a “strategic shift” in efforts to protect children from HIV, he had added, “Curing HIV-infected newborns.”
Stay tuned to Science Speaks Tuesday, April 30, for updates on the ramifications of the results of HVTN 505.