Why Haven’t Researchers Developed an HIV Vaccine or Cure Yet?
Kira Peikoff was the editor-in-chief of Leaps.org from 2017 to 2021. As a journalist, her work has appeared in The New York Times, Newsweek, Nautilus, Popular Mechanics, The New York Academy of Sciences, and other outlets. She is also the author of four suspense novels that explore controversial issues arising from scientific innovation: Living Proof, No Time to Die, Die Again Tomorrow, and Mother Knows Best. Peikoff holds a B.A. in Journalism from New York University and an M.S. in Bioethics from Columbia University. She lives in New Jersey with her husband and two young sons. Follow her on Twitter @KiraPeikoff.
Last week, top experts on HIV/AIDS convened in Amsterdam for the 22nd International AIDS conference, and the mood was not great. Even though remarkable advances in treating HIV have led to effective management for many people living with the disease, and its overall incidence has declined, there are signs that the virus could make a troubling comeback.
"In a perfect world, we'd get a vaccine like the HPV vaccine that was 100% effective and I think that's ultimately what we're going to strive for."
Growing resistance to current HIV drugs, a population boom in Sub-Saharan Africa, and insufficient public health resources are all poised to contribute to a second AIDS pandemic, according to published reports.
Already, the virus is nowhere near under control. Though the infection rate has declined 47 percent since its peak in 1996, last year 1.8 million people became newly infected with HIV around the world, and 37 million people are currently living with it. About 1 million people die of AIDS every year, making it the fourth biggest killer in low-income countries.
Leapsmag Editor-in-Chief Kira Peikoff reached out to Dr. Carl Dieffenbach, Director of the Division of AIDS at the National Institute of Allergy and Infectious Diseases, to find out what the U.S. government is doing to develop an HIV vaccine and cure. This interview has been edited and condensed for clarity.
What is the general trajectory of research in HIV/AIDS today?
We can break it down to two specific domains: focus on treatment and cure, and prevention.
Let's start with people living with HIV. This is the area where we've had the most success over the past 30 plus years, because we've taken a disease that was essentially a death sentence and converted it through the development of medications to a treatable chronic disease.
The second half of this equation is, can we cure or create a functional cure for people living with HIV? And the definition of functional cure would be the absence of circulating virus in the body in the absence of therapy. Essentially the human body would control the HIV infection within the individual. That is a much more, very early research stage of discovery. There are some interesting signals but it's still in need of innovation.
I'd like to make a contrast between what we are able to do with a virus called Hepatitis C and what we can do with the virus HIV. Hep C, with 12 weeks of highly active antiviral therapy, we can cure 95 to 100% of infections. With HIV, we cannot do that. The difference is the behavior of the virus. HIV integrates into the host's genome. Hep C is an RNA virus that stays in the cytoplasm of the cell and never gets into the DNA.
On the prevention side, we have two strategies: The first is pre-exposure prophylaxis. Then of course, we have the need for a safe, effective and durable HIV vaccine, which is a very active area of discovery. We've had some spectacular success with RV144, and we're following up on that success, and other vaccines are in the pipeline. Whether they are sufficient to provide the level of durability and activity is not yet clear, but progress has been made and there's still the need for innovation.
The most important breakthrough in the past 5 to 10 years has been the discovery of broad neutralizing monoclonal antibodies. They are proteins that the body makes, and not everybody who's HIV infected makes these antibodies, but we've been able to clone out these antibodies from certain individuals that are highly potent, and when used either singly or in combination, can truly neutralize the vast majority of HIV strains. Can those be used by themselves as treatment or as prevention? That is the question.
Can you explain more about RV144 and why you consider it a success?
Prior to RV144, we had run a number of vaccine studies and nothing had ever statistically shown to be protective. RV144 showed a level of efficacy of about 31 percent, which was statistically significant. Not enough to take forward into other studies, but it allowed us to generate some ideas about why this worked, go back to the drawing board, and redesign the immunogens to optimize and test the next generation for this vaccine. We just recently opened that new study, the follow-up to RV144, called HVTN702. That's up and enrolling and moving along quite nicely.
Carl Dieffenbach, Director of the Division of AIDS at the National Institute of Allergy and Infectious Diseases
(Courtesy)
Where is that enrolling?
Primarily in Sub-Saharan Africa and South Africa.
When will you expect to see signals from that?
Between 2020 and 2021. It's complicated because the signal also takes into account the durability. After a certain time of vaccination, we're going to count up endpoints.
How would you explain the main scientific obstacle in the way of creating a very efficacious HIV vaccine?
Simply put, it's the black box of the human immune system. HIV employs a shield technology, and the virus is constantly changing its shield to protect itself, but there are some key parts of the virus that it cannot shield, so that's the trick – to be able to target that.
So, you're trying to find the Achilles' Heel of the virus?
Exactly. To make a flu vaccine or a Zika vaccine or even an Ebola vaccine, the virus is a little bit more forthcoming with the target. In HIV, the virus does everything in its power to hide the target, so we're dealing with a well-adapted [adversary] that actively avoids neutralization. That's the scientific challenge we face.
What's next?
On the vaccine side, we are currently performing, in collaboration with partners, two vaccine trials – HVTN702, which we talked about, and another one called 705. If either of those are highly successful, they would both require an additional phase 3 clinical trial before they could be licensed. This is an important but not final step. Then we would move into scale up to global vaccination. Those conversations have begun but they are not very far along and need additional attention.
What percent of people in the current trials would need to be protected to move on to phase 3?
Between 50 and 60 percent. That comes with this question of durability: how long does the vaccine last?
It also includes, can we simplify the vaccine regimen? The vaccines we're testing right now are multiple shots over a period of time. Can we get more like the polio or smallpox vaccine, a shot with a booster down the road?
We're dealing with sovereign nations. We're doing this in partnership, not as helicopter-type researchers.
If these current trials pan out, do you think kids in the developed world will end up getting an HIV vaccine one day? Or just people in-at risk areas?
That's a good question. I don't have an answer to that. In a perfect world, we'd get a vaccine like the HPV vaccine that was 100% effective and I think that's ultimately what we're going to strive for. That's where that second or third generation of vaccines that trigger broad neutralizing antibodies come in.
With any luck at all, globally, the combination of antiretroviral treatment, pre-exposure prophylaxis and other prevention and treatment strategies will lower the incidence rate where the HIV pandemic continues to wane, and we will then be able to either target the vaccine or roll it out in a way that is both cost effective and destigmatizing.
And also, what does the country want? We're dealing with sovereign nations. We're doing this in partnership, not as helicopter-type researchers.
How close do you think we are globally to eradicating HIV infections?
Eradication's a big word. It means no new infections. We are nowhere close to eradicating HIV. Whether or not we can continue to bend the curve on the epidemic and have less infections so that the total number of people continues to decline over time, I think we can achieve that if we had the political will. And that's not just the U.S. political will. That's the will of the world. We have the tools, albeit they're not perfect. But that's where a vaccine that is efficacious and simple to deliver could be the gamechanger.
Kira Peikoff was the editor-in-chief of Leaps.org from 2017 to 2021. As a journalist, her work has appeared in The New York Times, Newsweek, Nautilus, Popular Mechanics, The New York Academy of Sciences, and other outlets. She is also the author of four suspense novels that explore controversial issues arising from scientific innovation: Living Proof, No Time to Die, Die Again Tomorrow, and Mother Knows Best. Peikoff holds a B.A. in Journalism from New York University and an M.S. in Bioethics from Columbia University. She lives in New Jersey with her husband and two young sons. Follow her on Twitter @KiraPeikoff.
Your phone could show if a bridge is about to collapse
In summer 2017, Thomas Matarazzo, then a postdoctoral researcher at the Massachusetts Institute of Technology, landed in San Francisco with a colleague. They rented two cars, drove up to the Golden Gate bridge, timing it to the city’s rush hour, and rode over to the other side in heavy traffic. Once they reached the other end, they turned around and did it again. And again. And again.
“I drove over that bridge 100 times over five days, back and forth,” says Matarazzo, now an associate director of High-Performance Computing in the Center for Innovation in Engineering at the United States Military Academy, West Point. “It was surprisingly stressful, I never anticipated that. I had to maintain the speed of about 30 miles an hour when the speed limit is 45. I felt bad for everybody behind me.”
Matarazzo had to drive slowly because the quality of data they were collecting depended on it. The pair was designing and testing a new smartphone app that could gather data about the bridge’s structural integrity—a low-cost citizen-scientist alternative to the current industrial methods, which aren’t always possible, partly because they’re expensive and complex. In the era of aging infrastructure, when some bridges in the United States and other countries are structurally unsound to the point of collapsing, such an app could inform authorities about the need for urgent repairs, or at least prompt closing the most dangerous structures.
There are 619,588 bridges in the U.S., and some of them are very old. For example, the Benjamin Franklin Bridge connecting Philadelphia to Camden, N.J., is 96-years-old while the Brooklyn Bridge is 153. So it’s hardly surprising that many could use some upgrades. “In the U.S., a lot of them were built in the post-World War II period to accommodate the surge of motorization,” says Carlo Ratti, architect and engineer who directs the Senseable City Lab at Massachusetts Institute of Technology. “They are beginning to reach the end of their life.”
According to the 2022 American Road & Transportation Builders Association’s report, one in three U.S. bridges needs repair or replacement. The Department of Transportation (DOT) National Bridge Inventory (NBI) database reveals concerning numbers. Thirty-six percent of U.S. bridges need repair work and over 78,000 bridges should be replaced. More than 43,500 bridges are rated in poor condition and classified as “structurally deficient” – an alarming description. Yet, people drive over them 167.5 million times a day. The Pittsburgh bridge which collapsed in January this year—only hours before President Biden arrived to discuss the new infrastructure law—was on the “poor” rating list.
Assessing the structural integrity of a bridge is not an easy endeavor. Most of the time, these are visual inspections, Matarazzo explains. Engineers check cracks, rust and other signs of wear and tear. They also check for wildlife—birds which may build nests or even small animals that make homes inside the bridge structures, which can slowly chip at the structure. However, visual inspections may not tell the whole story. A more sophisticated and significantly more expensive inspection requires placing special sensors on the bridge that essentially listen to how the bridge vibrates.
“Some bridges can afford expensive sensors to do the job, but that comes at a very high cost—hundreds of thousands of dollars per bridge per year,” Ratti says.
We may think of bridges as immovable steel and concrete monoliths, but they naturally vibrate, oscillating slightly. That movement can be influenced by the traffic that passes over them, and even by wind. Bridges of different types vibrate differently—some have longer vibrational frequencies and others shorter ones. A good way to visualize this phenomenon is to place a ruler over the edge of a desk and flick it slightly. If the ruler protrudes far off the desk, it will vibrate slowly. But if you shorten the end that hangs off, it will vibrate much faster. It works similarly with bridges, except there are more factors at play, including not only the length, but also the design and the materials used.
The long suspension bridges such as the Golden Gate or Verrazano Narrows, which hang on a series of cables, are more flexible, and their vibration amplitudes are longer. The Golden Gate Bridge can vibrate at 0.106 Hertz, where one Hertz is one oscillation per second. “Think about standing on the bridge for about 10 seconds—that's how long it takes for it to move all the way up and all the way down in one oscillation,” Matarazzo says.
On the contrary, the concrete span bridges that rest on multiple columns like Brooklyn Bridge or Manhattan Bridge, are “stiffer” and have greater vibrational frequencies. A concrete bridge can have a frequency of 10 Hertz, moving 10 times in one second—like that shorter stretch of a ruler.
The special devices that can pick up and record these vibrations over time are called accelerometers. A network of these devices for each bridge can cost $20,000 to $50,000, and more—and require trained personnel to place them. The sensors also must stay on the bridge for some time to establish what’s a healthy vibrational baseline for a given bridge. Maintaining them adds to the cost. “Some bridges can afford expensive sensors to do the job, but that comes at a very high cost—hundreds of thousands of dollars per bridge per year,” Ratti says.
Making sense of the readouts they gather is another challenge, which requires a high level of technical expertise. “You generally need somebody, some type of expert capable of doing the analysis to translate that data into information,” says Matarazzo, which ticks up the price, so doing visual inspections often proves to be a more economical choice for state-level DOTs with tight budgets. “The existing systems work well, but have downsides,” Ratti says. The team thought the old method could use some modernizing.
Smartphones, which are carried by millions of people, contain dozens of sensors, including the accelerometers capable of picking up the bridges’ vibrations. That’s why Matarazzo and his colleague drove over the bridge 100 times—they were trying to pick up enough data. Timing it to rush hour supported that goal because traffic caused more “excitation,” Matarazzo explains. “Excitation is a big word we use when we talk about what drives the vibration,” he says. “When there's a lot of traffic, there's more excitation and more vibration.” They also collaborated with Uber, whose drivers made 72 trips across the bridge to gather data in different cars.
The next step was to clean the data from “noise”—various vibrations that weren’t relevant to the bridge but came from the cars themselves. “It could be jumps in speed, it could be potholes, it could be a bunch of other things," Matarazzo says. But as the team gathered more data, it became easier to tell the bridge vibrational frequencies from all others because the noises generated by cars, traffic and other things tend to “cancel out.”
The team specifically picked the Golden Gate bridge because the civil structural engineering community had studied it extensively over the years and collected a host of vibrational data, using traditional sensors. When the researchers compared their app-collected frequencies with those gathered by 240 accelerometers formerly placed on the Golden Gate, the results were the same—the data from the phones converged with that from the bridge’s sensors. The smartphone-collected data were just as good as those from industry devices.
The study authors estimate that officials could use crowdsourced data to make key improvements that would help new bridges to last about 14 years longer.
The team also tested their method on a different type of bridge—not a suspension one like the Golden Gate, but a concrete span bridge in Ciampino, Italy. There they compared 280 car trips over the bridge to the six sensors that had been placed on the bridge for seven months. The results were slightly less matching, but a larger volume of trips would fix the divergence, the researchers wrote in their study, titled Crowdsourcing bridge dynamic monitoring with smartphone vehicle trips, published last month in Nature Communications Engineering.
Although the smartphones proved effective, the app is not quite ready to be rolled out commercially for people to start using. “It is still a pilot version,” so there’s room for improvement, says Ratti, who co-authored the study. “But on a more optimistic note, it has really low barriers to entry—all you need is smartphones on cars—so that makes the system easy to reach a global audience.” And the study authors estimate that the use of crowdsourced data would result in a new bridge lasting about 14 years longer.
Matarazzo hopes that the app could be eventually accessible for your average citizen scientist to collect the data and supply it to their local transportation authorities. “I hope that this idea can spark a different type of relationship with infrastructure where people think about the data they're collecting as some type of contribution or investment into their communities,” he says. “So that they can help their own department of transportation, their own municipality to support that bridge and keep it maintained better, longer and safer.”
Lina Zeldovich has written about science, medicine and technology for Popular Science, Smithsonian, National Geographic, Scientific American, Reader’s Digest, the New York Times and other major national and international publications. A Columbia J-School alumna, she has won several awards for her stories, including the ASJA Crisis Coverage Award for Covid reporting, and has been a contributing editor at Nautilus Magazine. In 2021, Zeldovich released her first book, The Other Dark Matter, published by the University of Chicago Press, about the science and business of turning waste into wealth and health. You can find her on http://linazeldovich.com/ and @linazeldovich.
The Friday Five: Sugar could help catch cancer early
The Friday Five covers five stories in research that you may have missed this week. There are plenty of controversies and troubling ethical issues in science – and we get into many of them in our online magazine – but this news roundup focuses on scientific creativity and progress to give you a therapeutic dose of inspiration headed into the weekend.
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Here are the promising studies covered in this week's Friday Five:
- Catching cancer early could depend on sugar
- How to boost memory in a flash
- This is your brain on books
- A tiny sandwich cake could help the heart
- Meet the top banana for fighting Covid variants