Why Haven’t Researchers Developed an HIV Vaccine or Cure Yet?

Why Haven’t Researchers Developed an HIV Vaccine or Cure Yet?

A blood test for analysis of HIV.

(© angellodeco/Fotolia)



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

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.

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David Waltner-Toews

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One stall offered Giant Asian hornets, both babies and adults. I suppressed my inner squirm and, in the interests of world food security and equity, accepted an offer of the soft, velvety larva; they were smooth on the tongue and of a pleasantly cool, buttery-custard consistency. Because the seller had already given me a free sample, I felt obliged to buy a chunk of the nest with larvae and some dead adults, which the seller mixed with kaffir lime leaves.

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David Waltner-Toews
David Waltner-Toews is a veterinary epidemiologist and author of more than twenty books of poetry, fiction, and science. His most recent books are On Pandemics: deadly diseases from bubonic plague to coronavirus (Greystone Books, 2020); Eat the Beetles: an exploration into our conflicted relationship with insects (ECW Press, 2017) and The Origin of Feces: what excrement tells us about evolution, ecology and a sustainable society (ECW Press, 2013).
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Plowright is a Cornell Atkinson Scholar and professor at Cornell in the Department of Public and Ecosystem Health in the College of Veterinary Medicine. Read her full bio here. For a shorter (and lightly edited) version of this conversation, you can check out my Q&A interview with Plowright in the single-issue magazine, One Health / One Planet, published earlier this month by Leaps.org in collaboration with the Aspen Institute and the Science Philanthropy Alliance.

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