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.
With the population of older people projected to grow dramatically, and the cost of healthcare with it, the future welfare of the country may depend on solving aging, writes philosopher Ingemar Patrick Linden.
There is a lack of political will and leadership on the issue, and the idea that we should seek to do something about aging is generally met with a great deal of suspicion and trepidation. In a large representative study conducted by the Pew Research Center in 2013, only 38% of the respondents said that they would want a treatment that could slow the aging process and allow them to live at least 120 years. Apparently, most people prefer, or at least do not mind, to age and die within a natural lifespan. This result has been confirmed by smaller studies and it is, I think, surprising. Are we not supposed to live in a youth-culture? Are people not supposed to want to stay young and alive forever? Is self-preservation not the strong drive we have always assumed it to be?
We are inundated and saturated with an ideology of death-acceptance.
In my book, The Case against Death, I suggest that we have been culturally conditioned to think that it is virtuous to accept aging and death. We are taught to believe that although aging and death seem gruesome, they are what is best for us, all things considered. This is what we are supposed to think, and the majority accept it. I call this the Wise View because death acceptance has been the dominant view of philosophers since the beginning. Socrates compared our earthly life to an illness and a prison and described death as a healer and a liberator. The Buddha taught that life is suffering and that the way to escape suffering is to end the cycle of birth, death and rebirth. Stoic philosophers from Zeno to Marcus Aurelius believed that everything that happens in accordance with nature is good, and that therefore we should not only accept death but welcome it as an aspect of a perfect totality.
Epicureans agreed with these rival schools and famously argued that death cannot harm us because where we are, death is not, and where death is we are not. We cannot be harmed if we are not, so death is harmless. The simple view that death actually can harm us greatly is one of the least philosophical views one can hold.
In The Case Against Death, philosopher Ingemar Patrick Linden argues that we frown on using science to prolong healthy life only because we're culturally conditioned to think that way.
Many of the stories we tell promote the Wise View. One of the earliest known pieces of literature, the Epic of Gilgamesh, follows Gilgamesh on a quest for eternal life ending with the wisdom that death is the destiny of man. Today we learn about the tedium of immortality from the children’s book Tuck Everlasting by Natalie Babbitt, and we are warned about the vice of wanting to resist death in other books and films such as J.K Rowling’s Harry Potter, where Voldemort must kill Harry as a step towards his own immortality; C.S. Lewis’ The Chronicles of Narnia where the White Witch has gained immortal youth and madness in equal measures; J.R.R. Tolkien’s Lord of the Rings trilogy where the ring extends the wearer’s life but can also destroy them, as exemplified by the creep Gollum; and Doctor Strange where life extension is the one magical power that is taboo. In Star Wars, Yoda, a stereotype of the sage, teaches us the wisdom handed down by philosophers and prophets: “Death is a natural part of life. Rejoice for those around you who transform into the Force. Mourn them do not. Miss them do not.”
We are inundated and saturated with an ideology of death-acceptance. Can the dear reader name one single story where the hero is pursuing anti-aging, longevity or immortality and the villain tries to stop her?
The Wise View resonates with us partly because we think that there is nothing we can do about aging and death, so we do not want to wish for what we cannot have. Youth and immortality are sour grapes to us. Believing that death is, all things considered, not such a bad thing, protects us from experiencing our aging and approaching death as a gruesome tragedy. This need to escape the thought that we are heading towards a personal catastrophe explains why many are so quick to accept arguments against radical life extension, despite their often glaring weaknesses.
One of the most common objections to radical life extension is that aging and death are natural. The problem with this argument is that many things that are natural are very bad, such as cancer, and other things that are not natural are very good, such as a cure for cancer. Why are we so sure that cancer is bad? Because we assume that it is bad to die. Indeed, nothing is more natural than wanting to live. We seem to need philosophers and story tellers to talk us out of it and, in the words of a distinguished bioethicist, “instruct and somewhat moderate our lust for life.”
Another standard objection is that we need a deadline, and that without death we could postpone every action forever. “Death brings urgency and seriousness to life,” say proponents of this view, but there are several problems with this argument. Even if our lives were endless, there would still be many things we would have to do at a certain time, and that could not be redone, for example, saving our planet from being destroyed, or becoming the first person on Venus. And if we prefer pleasant endless lives over unpleasant endless ones, we will have to exercise, eat right, keep our word, develop our talents, show up for time at work, pay our taxes by the due date, remember birthdays, and so on.
The Wise View provides us with a feel-good bromide for the anxiety created by the foreknowledge of our decay and death by telling us that these are not evils, but blessings in disguise. Once perhaps an innocuous delusion, today the view stands in the way of a necessary societal commitment to research that can prolong our healthy life.
Besides, even if we succeeded in ending aging, we would still die from other causes. Given the rate of accidental deaths we would be fortunate to live to age 2000 all things equal. So even if, contrary to what I have argued, we do need a deadline, we can still argue that the natural lifespan that we now labor under is inhuman and that it forces each human to limit her ambitions and to become only a fragment of all that she that could have been. Our tight time constraint imposes tragic choices and inflated opportunity costs. Death does not make life matter; it makes time matter.
The perhaps most awful argument against radical life extension is grounded in a pessimism that holds life in such little regard that it says that best of all is never to have born. This view was expressed by Ecclesiastes in the Hebrew Bible, by Sophocles and several other ancient Greeks, by the German philosopher Arthur Schopenhauer, and recently by, among others, the South African philosopher David Benatar who argues that it is wrong to bring children into the world and that we should euthanize all sentient life. Pessimism, one suspects, largely appeals to some for reasons having to do with personal temperament, but insofar as it is built on factual beliefs, they can be addressed by providing a less negatively biased understanding of the world, by pointing out that curing aging would decrease the badness that they are so hypersensitive to, and by reminding them that if life really becomes unbearable, they are free to quit at any time. Other means of persuasion could include recommending sleep, exercise and taking long brisk walks in nature.
The Wise View provides us with a feel-good bromide for the anxiety created by the foreknowledge of our decay and death by telling us that these are not evils, but blessings in disguise. Once perhaps an innocuous delusion, today the view stands in the way of a necessary societal commitment to research that can prolong our healthy life. We need abandon it and openly admit that aging is a scourge that deserves to be fought with the combined energies equaling those expended on fighting COVID-19, Alzheimer’s disease, cancer, stroke and all the other illnesses for which aging is the greatest risk factor. The fight to end aging transcends ordinary political boundaries and is therefore the kind of grand unifying enterprise that could re-energize a society suffering from divisiveness and the sense of a lack of a common purpose. It is hard to imagine a more worthwhile cause.