A blood test for analysis of HIV.
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.
Donna Shirley pictured at her home in Tulsa, with a model of the Sojourner rover she was in charge of that explored Mars.
"Periodically, I'll hear somebody say they got into the space program because of me, and that makes me feel really good," Shirley told Leaps.org. "I look at the mission control area, and there are a lot of women in there. I'm quite pleased I was able to break the glass ceiling."
Her $25-million, 25-pound microrover – powered by solar energy and designed to get rock samples and test soil chemistry for evidence of life – was named after Sojourner Truth, a 19th-century Black abolitionist and women's rights activist. Unlike Mars Pathfinder, Shirley didn't have to travel more than 131 million miles to reach her goal, but her path to scientific fame as a woman sometimes resembled an asteroid field.
The Sojourner Rover in 1997 on Mars.NASA/JPLAs a high-IQ tomboy growing up in Wynnewood, Oklahoma (pop. 2,300), Shirley yearned to escape. She decided to become an engineer at age 10 and took flying lessons at 15. Her extraterrestrial aspirations were fueled by Ray Bradbury's The Martian Chronicles and Arthur C. Clarke's The Sands of Mars. Yet when she entered the University of Oklahoma (OU) in 1958, her freshman academic advisor initially told her: "Girls can't be engineers." She ignored him.
Years later, Shirley would combat such archaic thinking, succeeding at JPL with her creative, collaborative management style. "If you look at the literature, you'll find that teams that are either led by or heavily involved with women do better than strictly male teams," she noted.
However, her career trajectory stalled at OU. Burned out by her course load and distracted by a broken engagement to marry a fellow student, she switched her major to professional writing. After graduation, she applied her aeronautical background as a McDonnell Aircraft technical writer, but her boss, she says, harassed her and she faced gender-based hostility from male co-workers.
Returning to OU, Shirley finished off her engineering degree and became a JPL aerodynamist in 1966 after answering an ad in the St. Louis Post-Dispatch. At first, she was the only female engineer among the research center's 2,000-odd engineers. She wore many hats, from designing planetary atmospheric entry vehicles to picking the launch date of November 4, 1973 for Mariner 10's mission to Venus and Mercury.
By the mid-1980's, she was managing teams that focused on robotics and Mars, delivering creative solutions when NASA budget cuts loomed. In 1989, the same year the Sojourner microrover concept was born, President George H.W. Bush announced his Space Exploration Initiative, including plans for a human mission to Mars by 2019.
That target, of course, wasn't attained, despite huge advances in technology and our understanding of the Martian environment. Today, Shirley believes humans could land on Mars by 2030. She became the founding director of the Science Fiction Museum and Hall of Fame in Seattle in 2004 after leaving NASA, and to this day, she enjoys checking out pop culture portrayals of Mars landings – even if they're not always accurate.
After the novel The Martian was published in 2011, which later was adapted into the hit film starring Matt Damon, Shirley phoned author Andy Weir: "You've got a major mistake in here. It says there's a storm that tries to blow the rocket over. But actually, the Mars atmosphere is so thin, it would never blow a rocket over!"
Fearlessly speaking her mind and seeking the stars helped Donna Shirley make history. However, a 2019 Washington Post story noted: "Women make up only about a third of NASA's workforce. They comprise just 28 percent of senior executive leadership positions and are only 16 percent of senior scientific employees." Whether it's traveling to Mars or trending toward gender equality, we've still got a long way to go.