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.
Doctors used new eye drops to treat a rare genetic disorder.
The gene therapy: In May 2023, the FDA approved Vyjuvek, the first gene therapy to treat DEB.
Vyjuvek uses an inactivated herpes simplex virus to deliver working copies of the gene for collagen 7 to the body’s cells. In small trials, 65 percent of DEB-caused wounds sprinkled with it healed completely, compared to just 26 percent of wounds treated with a placebo.
“It was like looking through thick fog.” -- Antonio Vento Carvajal.
The patient: Antonio Vento Carvajal, a 14 year old living in Florida, was one of the trial participants to benefit from Vyjuvek, which was developed by Pittsburgh-based pharmaceutical company Krystal Biotech.
While the topical gene therapy could help his skin, though, it couldn’t do anything to address the severe vision loss Antonio experienced due to his DEB. He’d undergone multiple surgeries to have scar tissue removed from his eyes, but due to his condition, the blisters keep coming back.
“It was like looking through thick fog,” said Antonio, noting how his impaired vision made it hard for him to play his favorite video games. “I had to stand up from my chair, walk over, and get closer to the screen to be able to see.”
The idea: Encouraged by how Antonio’s skin wounds were responding to the gene therapy, Alfonso Sabater, his doctor at the Bascom Palmer Eye Institute, reached out to Krystal Biotech to see if they thought an alternative formula could potentially help treat his patient’s eyes.
The company was eager to help, according to Sabater, and after about two years of safety and efficacy testing, he had permission, under the FDA’s compassionate use protocol, to treat Antonio’s eyes with a version of the topical gene therapy delivered as eye drops.
The results: In August 2022, Sabater once again removed scar tissue from Antonio’s right eye, but this time, he followed up the surgery by immediately applying eye drops containing the gene therapy.
“I would send this message to other families in similar situations, whether it’s DEB or another condition that can benefit from genetic therapy. Don’t be afraid.” -- Yunielkys “Yuni” Carvajal.
The vision in Antonio’s eye steadily improved. By about eight months after the treatment, it was just slightly below average (20/25) and stayed that way. In March 2023, Sabater performed the same procedure on his young patient’s other eye, and the vision in it has also steadily improved.
“I’ve seen the transformation in Antonio’s life,” said Sabater. “He’s always been a happy kid. Now he’s very happy. He can function pretty much normally. He can read, he can study, he can play video games.”
Looking ahead: The topical gene therapy isn’t a permanent fix — it doesn’t alter Antonio’s own genes, so he has to have the eye drops reapplied every month. Still, that’s far less invasive than having to undergo repeated surgeries.
Sabater is now working with Krystal Biotech to launch trials of the eye drops in other patients, and not just those with DEB. By changing the gene delivered by the therapy, he believes it could be used to treat other eye disorders that are far more common — Fuchs’ dystrophy, for example, affects the vision of an estimated 300 million people over the age of 30.
Antonio’s mother, Yunielkys “Yuni” Carvajal, meanwhile, has said that having her son be the first to receive the eye drops was “very scary,” but she’s hopeful others will take a chance on new gene therapies if given the opportunity.
“I would send this message to other families in similar situations, whether it’s DEB or another condition that can benefit from genetic therapy,” she said. “Don’t be afraid.”
This article originally appeared on Freethink, home of the brightest minds and biggest ideas of all time.
A chatbot from the nonprofit National Eating Disorders Association aimed to provide 24/7 guidance on eating disorders. Several drawbacks point to the importance of therapist-tech collaboration in multiple areas of health.
Then everything went off the rails. Tessa told Maxwell an unequivocal yes, and that “it’s important to approach weight loss with a balanced and realistic mindset,” and recommended eating whole foods and lean proteins to create a 500-1000 calorie per day deficit that would lead to a loss of 1-2 pounds per week. To most people, the advice sounds anodyne, but alarm bells sounded in Maxwell’s head.
“This is actively going to feed eating disorders,” Maxwell says. “Having a chatbot be the direct response to someone reaching out for support for an eating disorder instead of the helpline seems careless.”
“The scripts that are being fed into the chatbot are only going to be as good as the person who’s feeding them.” -- Alexis Conason.
According to several decades of research, deliberate weight loss in the form of dieting is a serious risk for people with eating disorders. Maxwell says that following medical advice like what Tessa prescribed was what triggered her eating disorder as a child. And Maxwell wasn’t the only one who got such advice from the bot. When eating disorder therapist Alexis Conason tried Tessa, she asked the AI chatbot many of the questions her patients had. But instead of getting connected to resources or guidance on recovery, Conason, too, got tips on losing weight and “healthy” eating.
“The scripts that are being fed into the chatbot are only going to be as good as the person who’s feeding them,” Conason says. “It’s important that an eating disorder organization like NEDA is not reinforcing that same kind of harmful advice that we might get from medical providers who are less knowledgeable.”
Maxwell’s post about Tessa on Instagram went viral, and within days, NEDA had scrubbed all evidence of Tessa from its website. The furor has raised any number of issues about the harm perpetuated by a leading eating disorder charity and the ongoing influence of diet culture and advice that is pervasive in the field. But for AI experts, bears and bulls alike, Tessa offers a cautionary tale about what happens when a still-immature technology is unfettered and released into a vulnerable population.
Given the complexity involved in giving medical advice, the process of developing these chatbots must be rigorous and transparent, unlike NEDA’s approach.
“We don’t have a full understanding of what’s going on in these models. They’re a black box,” says Stephen Schueller, a clinical psychologist at the University of California, Irvine.
The health crisis
In March 2020, the world dove head-first into a heavily virtual world as countries scrambled to try and halt the pandemic. Even with lockdowns, hospitals were overwhelmed by the virus. The downstream effects of these lifesaving measures are still being felt, especially in mental health. Anxiety and depression are at all-time highs in teens, and a new report in The Lancet showed that post-Covid rates of newly diagnosed eating disorders in girls aged 13-16 were 42.4 percent higher than previous years.
And the crisis isn’t just in mental health.
“People are so desperate for health care advice that they'll actually go online and post pictures of [their intimate areas] and ask what kind of STD they have on public social media,” says John Ayers, an epidemiologist at the University of California, San Diego.
For many people, the choice isn’t chatbot vs. well-trained physician, but chatbot vs. nothing at all.
I know a bit about that desperation. Like Maxwell, I have struggled with a multi-decade eating disorder. I spent my 20s and 30s bouncing from crisis to crisis. I have called suicide hotlines, gone to emergency rooms, and spent weeks-on-end confined to hospital wards. Though I have found recovery in recent years, I’m still not sure what ultimately made the difference. A relapse isn't improbably, given my history. Even if I relapsed again, though, I don’t know it would occur to me to ask an AI system for help.
For one, I am privileged to have assembled a stellar group of outpatient professionals who know me, know what trips me up, and know how to respond to my frantic texts. Ditto for my close friends. What I often need is a shoulder to cry on or a place to vent—someone to hear and validate my distress. What’s more, my trust in these individuals far exceeds my confidence in the companies that create these chatbots. The Internet is full of health advice, much of it bad. Even for high-quality, evidence-based advice, medicine is often filled with disagreements about how the evidence might be applied and for whom it’s relevant. All of this is key in the training of AI systems like ChatGPT, and many AI companies remain silent on this process, Schueller says.
The problem, Ayers points out, is that for many people, the choice isn’t chatbot vs. well-trained physician, but chatbot vs. nothing at all. Hence the proliferation of “does this infection make my scrotum look strange?” questions. Where AI can truly shine, he says, is not by providing direct psychological help but by pointing people towards existing resources that we already know are effective.
“It’s important that these chatbots connect [their users to] to provide that human touch, to link you to resources,” Ayers says. “That’s where AI can actually save a life.”
Before building a chatbot and releasing it, developers need to pause and consult with the communities they hope to serve.
Unfortunately, many systems don’t do this. In a study published last month in the Journal of the American Medical Association, Ayers and colleagues found that although the chatbots did well at providing evidence-based answers, they often didn’t provide referrals to existing resources. Despite this, in an April 2023 study, Ayers’s team found that both patients and professionals rated the quality of the AI responses to questions, measured by both accuracy and empathy, rather highly. To Ayers, this means that AI developers should focus more on the quality of the information being delivered rather than the method of delivery itself.
Many mental health professionals have months-long waitlists, which leaves individuals to deal with illnesses on their own.
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The human touch
The mental health field is facing timing constraints, too. Even before the pandemic, the U.S. suffered from a shortage of mental health providers. Since then, the rates of anxiety, depression, and eating disorders have spiked even higher, and many mental health professionals report waiting lists that are months long. Without support, individuals are left to try and cope on their own, which often means their condition deteriorates even further.
Nor do mental health crises happen during office hours. I struggled the most late at night, long after everyone else had gone to bed. I needed support during those times when I was most liable to hurt myself, not in the mornings and afternoons when I was at work.
In this sense, a 24/7 chatbot makes lots of sense. “I don't think we should stifle innovation in this space,” Schueller says. “Because if there was any system that needs to be innovated, it's mental health services, because they are sadly insufficient. They’re terrible.”
But before building a chatbot and releasing it, Tina Hernandez-Boussard, a data scientist at Stanford Medicine, says that developers need to pause and consult with the communities they hope to serve. It requires a deep understanding of what their needs are, the language they use to describe their concerns, existing resources, and what kinds of topics and suggestions aren’t helpful. Even asking a simple question at the beginning of a conversation such as “Do you want to talk to an AI or a human?” could allow those individuals to pick the type of interaction that suits their needs, Hernandez-Boussard says.
NEDA did none of these things before deploying Tessa. The researchers who developed the online body positivity self-help program upon which Tessa was initially based created a set of online question-and-answer exercises to improve body image. It didn’t involve generative AI that could write its own answers. The bot deployed by NEDA did use generative AI, something that no one in the eating disorder community was aware of before Tessa was brought online. Consulting those with lived experience would have flagged Tessa’s weight loss and “healthy eating” recommendations, Conason says.
The question for healthcare isn’t whether to use AI, but how.
NEDA did not comment on initial Tessa’s development and deployment, but a spokesperson told Leaps.org that “Tessa will be back online once we are confident that the program will be run with the rule-based approach as it was designed.”
The tech and therapist collaboration
The question for healthcare isn’t whether to use AI, but how. Already, AI can spot anomalies on medical images with greater precision than human eyes and can flag specific areas of an image for a radiologist to review in greater detail. Similarly, in mental health, AI should be an add-on for therapy, not a counselor-in-a-box, says Aniket Bera, an expert on AI and mental health at Purdue University.
“If [AIs] are going to be good helpers, then we need to understand humans better,” Bera says. That means understanding what patients and therapists alike need help with and respond to.
One of the biggest challenges of struggling with chronic illness is the dehumanization that happens. You become a patient number, a set of laboratory values and test scores. Treatment is often dictated by invisible algorithms and rules that you have no control over or access to. It’s frightening and maddening. But this doesn’t mean chatbots don’t have any place in medicine and mental health. An AI system could help provide appointment reminders and answer procedural questions about parking and whether someone should fast before a test or a procedure. They can help manage billing and even provide support between outpatient sessions by offering suggestions for what coping skills to use, the best ways to manage anxiety, and point to local resources. As the bots get better, they may eventually shoulder more and more of the burden of providing mental health care. But as Maxwell learned with Tessa, it’s still no replacement for human interaction.
“I'm not suggesting we should go in and start replacing therapists with technologies,” Schueller says. Instead, he advocates for a therapist-tech collaboration. “The technology side and the human component—these things need to come together.”