Illustrations by Felix Santos
“It is no longer the science that is limiting
a cure for AIDS,
but a failure of leadership and the lack of imagination,”
says Kambiz Shekdar, an Iranian-born cellular biologist who invented biotechnology that puts innovative stem cell therapy into practice. His nonprofit organization RFTCA (Research Foundation To Cure AIDS) is the first charitable biotechnology venture that obtained a license to use cellular technology to research, develop, and commercialize a global cure for HIV/AIDS for all those in need, regardless of ability to pay.
I first met Kambiz during World AIDS Day in 2019. His nonprofit was hosting a fundraising gala at Indochine, the iconic NYC restaurant. During his opening speech at the gala, I was taken aback by his bold statement that getting rid of HIV/AIDS was plausible and scientifically conceivable. There are only two reported cases of people cured of AIDS. Timothy Ray Brown, otherwise known as the “Berlin patient” was cured in 2007, and Adam Castillejo, also known as “London patient” was cured in 2019, as reported by The New York Times. It was hard to believe that a cure might be just around the corner, when the success rate of getting rid of the disease was so miniscule. Nonetheless, I wanted to find out more about Kambiz and the work that he was doing with RFTCA.
Just a month later I found myself sitting in Kambiz’ spacious Brooklyn apartment, deluged with a wide selection of cheese, fruits, and hot tea.
Kambiz: I am a gay guy, I grew up with AIDS always in the background, as something that I would have to face as a gay guy, and I care about the disease on a personal level, but why I decided to start RFTCA was only from a scientific standpoint.
There are about 37 million people around the world living with HIV/AIDS, and only two people have been cured. One of the technologies that I invented when I was a graduate student at Rockefeller University is something we built a biotech company around, and we’ve been applying that technology to many different uses for almost 20 years. It’s like a Swiss army knife that you can take to different projects. This technology has promised to take the only two known cures of AIDS to date, learn from them, and translate them into a broadly accessible cure, something that you could imagine could be available to everyone around the world who has HIV/AIDS.
Kambiz refers to his technology as disruptive. Disruptive technology is an innovation that significantly alters the way that consumers, industries, or businesses operate. A disruptive technology sweeps away the systems or habits it replaces because it has attributes that are recognizably superior.
When I heard about the first person who was cured, I realized that biotechnology I invented and built a biotech firm around promised to translate the science behind the first cures into basically a cookie-cutter cure that would be more readily available for more people. And I decided that we were just going to start and try to figure out how to make that happen.
The AIDS drugs that have been life-saving are amazing – they’ve kept millions of people from dying. But there’s an almost singular focus on these drugs, there is so much money behind the drugs, and the drug makers are paying LGBT/HIV organizations hundreds of millions of dollars, so everyone is promoting the drugs, everyone is talking about the drugs, and very few people have heard that two people were cured of AIDS.
The science for developing a robust, broadly applicable cure is just starting to bubble up. Very few people know about it. So it’s very important to raise awareness that this science is on the horizon – and that this is the time to really push all possible effort towards a cure.
Alexey: Right now, I feel like it’s all about the medicine, it’s all about PrEP. I heard about the Berlin patient before, but I feel like not everyone was talking about it and it wasn’t featured in the news. I thought it was a fluke. If they cured that one person, why haven’t they cured more people?
Kambiz: If you cured a disease – let’s say you cured colon cancer for the first time – it doesn’t mean that future cures are going to be the same way as the first time around. Future cures could be much more streamlined and different. The first patients that were cured of AIDS had both AIDS and leukemia. For leukemia you do a bone marrow transplant, you take bone marrow or stem cells from the donor and you put it in the patient where the stem cells give rise to a new immune system that cures the leukemia.
Kambiz: The doctor who cured the first AIDS patient was a hematologist. His patient had leukemia and AIDS, and he had heard in medical school that some people are naturally HIV resistant. He thought,
“We have to cure the patient’s leukemia, but the patient also has AIDS, let’s look for a donor who’s not only immune matched but one of the handful of people who is known to be naturally resistant to HIV. If we take stem cells from the bone marrow of someone who’s HIV resistant and put them in the AIDS patient, maybe the immune system will not only cure the patient’s leukemia but also AIDS.”
And it worked!
What’s interesting is it was a doctor treating leukemia who cured AIDS-it wasn’t an AIDS physician or an AIDS scientist-the idea came from left field. That is one reason the news of the cure didn’t catch on, because it was reported by a doctor who was not an expert in the space. At first many people didn’t believe it, they thought it was a fluke, maybe the guy is a wacko. Yet this patient was tested over and over again and remained HIV negative, and eventually it was clear that he had been cured. There were still lots of questions. What exactly cured him? Could it have been the wiping out of the cancerous immune system? When the second patient was cured it became clear it wasn’t a fluke, that it was repeatable. It was still a convoluted process, it still needed to be straightened out, but the second cure showed that this is not a one-time thing, it’s now been done twice. It meant that the cure could be repeated.
Alexey: What makes someone resistant to HIV?
Kambiz: There may be many ways people are resistant. In the early days of AIDS, some people who became positive would progress to having AIDS illness faster than others, and people thought not much of it, like, you know, everyone has different luck or different health, but it may be that there’s a biological basis for how people respond to HIV infection.
At least one of the factors is a gene called CCR5. Let’s say HIV infects your cells. The virus latches on to the surface of your cells and it injects its genetic material. It takes over the cell. That’s how the cell becomes infected, but the virus doesn’t just attach anywhere on the cell. There are cellular receptors on the surface of the cell, and like a boat at a dock, the virus latches on really tightly to these. HIV has to attach to two cellular factors present on the surface of cells: CD4 and CCR5.
People have different versions of genes. Some people have a shorter version of the CCR5 gene – called CCR5-Δ32 (delta-32). It’s missing 32 letters of DNA. This is a big change, making it a different version. Let’s say, the normal version is this long; the Delta32 mutation is a little bit shorter, the shortening disables the CCR5 receptor on white blood cells and people with the shortened gene may have a natural defense mechanism against HIV infection. Just like when different genes can give you blue, green, or brown eyes, people with this genetic mutation happen to be HIV resistant because the virus just can’t latch onto the cells of an individual who has the shortened CCR5 receptor. So no matter how many times they might be exposed to the virus, it simply cannot grip onto them, it can’t infect their cells. This biology was first discovered during the height of the AIDS epidemic when lots of gay men were dying.
Some gay men whose friends were dying started going to doctors and saying,
“I have the same risk factors as my friends who are dying.”
They had the same kind of sex with multiple partners and were doing the same things, yet they were not being infected. So after a while, after studying them, doctors found out that these guys happened to have a shortened version of this gene, and that became known.
It was known for many years that at least 10% of people of northern European descent have the short genetics and are resistant, and there are thousands of people with AIDS and leukemia, and anyone could have thought,
“Let’s cure the leukemia and these patients using bone marrow from one of these resistant donors,”
but no one else thought to do that.
Alexey: So why is it such a challenge to cure AIDS in the first place? Can you tell me a little bit more about the disease itself?
Kambiz: You know I’m not an HIV/AIDS expert. My expertise is in cellular engineering or genetic engineering. And I’m venturing into a genetic engineering method that we can apply to different genes including HIV-related genes. So we bring this expertise to the HIV space. As I understand it, HIV is a virus that infects cells of the immune system. Immune cells are your body’s natural defense system and this virus infects these cells, destroying your immune system. Once your immune system is gone, you can’t fight off infections that normally would not be a problem. So you succumb to diseases that ordinary healthy people would survive, but they become life and death in the case of AIDS.
Alexey: So in the case of the Berlin patient and the London patient, that infection was scrubbed out of their system?
Kambiz: As far as people can tell by the tests, that is possible. They can’t detect the living virus in the patient’s system.
Alexey: And are you implementing the knowledge that you got from these two patients into your technology?
Kambiz: Yes. The two patients were cured using naturally occurring stem cells from the rare donors that are naturally HIV resistant. Physicians took stem cells from the rare donors, put them in the patients, and that showed what kinds of stem cells are cured. Where we and several groups like ours come in, is using our own different genetic engineering technologies, including technologies like CRISPR and others, to create curative cells using each person’s own stem cells.
The idea is, if I have HIV/AIDS, you would take my blood’s free-floating stem cells. They reside in the bone marrow, but these stem cells also circulate in your blood and go back into the bone marrow and come out again. Ideally, this is what a cure would look like: doctors would draw blood, isolate the stem cells from your blood, and then we come in to do the genetic surgery to shorten that CCR5 gene in the cells. We would take the 32 letters out in a patient’s own stem cells and then infuse the stem cells back into the patient, no longer needing the donor. That’s the idea.
There are four or five different ways to do the genetic surgery. The technology I invented when I was a graduate student is one of them, and what we are working to do at RFTCA is to develop it for use to cure HIV/AIDS on a pro bono basis. We’ve fully licensed our technology to RFTCA, so that the organization has the rights to research, develop, and commercialize a charitable cure. The next step is us saying,
“We’ve put the technology on the table, now we need the funding to build a team of scientists to adapt the technology and optimize it for this purpose.”
We’ve used the technology in other applications, but we haven’t yet used it for HIV/AIDS. That’s what we’re starting to do.
Alexey: Do you need more funding to start trying it on HIV patients?
Kambiz: That’s one of the things we need. We also need a lab. We’re currently talking with Northwell Health. Northwell is a huge hospital complex. They own 20-plus hospitals in the New York area. And one of these hospitals is the former St. Vincent’s Hospital in New York City. St. Vincent’s was the center for compassionate care for HIV/AIDS patients in New York City and hundreds, maybe thousands of patients, died of AIDS at St. Vincent’s Hospital right in the West Village at Greenwich Avenue and 7th Avenue. That hospital closed down and is now owned by Northwell Health. We’re talking with Northwell about creating our research lab in the very space of the former AIDS ward of St. Vincent’s. We’re also starting to talk with the city to help get city funds to build out the labs. With the technology and the lab, what we need next is funding to actually hire the scientists and the full team to do this project.
Alexey: At the Indochine gala you mentioned that it was hard for you to get funding. Your goal was to get one million dollars to set you on the next step. And you said that it was challenging getting that much in donations.
Kambiz: Very difficult. I don’t have a lot of friends who can easily write a big check. So to reach people who, out of the goodness of their hearts, decide they want to give their money to this and not get anything in return except knowing they’re moving something forward is challenging. I’m sure a lot of people out there would care about this project and want to support it, but they don’t know that we exist. They don’t know that curing AIDS is really thinkable. They don’t know that there are groups out there like ours trying to bring the science forward. Reaching those people who are in a position to write big checks and telling them,
“You know, there’s no crystal balls in science, but we believe we have a promising pathway,”
and asking for their support, is really difficult.
Alexey: It probably is also difficult to build that trust bridge. If I were a millionaire and then you told me about this, I would probably just give you a million right away, but I can see how people might think that it’s impossible or, why haven’t they heard of the Berlin patient or where’s the proof that this is actually going to work? At the same time I think that maybe also the problem is that the focus is on a different thing. These medications are saving a lot of lives, but at the same time they are kind of taking up all of the headspace of everyone at the moment. That’s what everyone’s just thinking about.
Kambiz: When I first started this organization, I thought it would be very easy to get money given what we set out to do. I didn’t even think it would be much of an effort, but I had never been in a nonprofit. I thought there’d be tons of people who would happily give us checks to get started. I came across a couple of different obstacles. One is stigma. In medical philanthropy, usually the people who donate to fund the leading edge of innovation are either patients who are driven to help their own condition or those who feel like they’ve suffered through something and can relate – then it becomes a cause for them and they want to help address it. In the case of HIV/AIDS, this social stigma has been so strong and it is still so strong that a lot of people who are in a position to donate money don’t want to be known as having HIV/AIDS. There’s a barrier to being up front about it unlike, say, cancer. Social stigma makes it harder for some people to really get involved. I know some older gay guys who are HIV-positive where very few people know they are HIV-positive, and they keep it a closely guarded secret.
I also know a few young gay guys who are HIV-positive whose family has a lot of money, and it’s the same thing for them. The last thing they want is for people to know their kid is HIV-positive. They’d rather have the kid go on with his life with the best medical care and for no one to know they are positive. So if medical philanthropy is driven by patients, but stigma keeps a lot of the patients who can fund this kind of in the shadows, that’s one obstacle.
The second obstacle is just the vast amount of money in the drug space. We have a lot of terrific organizations like GMHC that have been around for 30-plus years.
Their biggest corporate donor is Gilead.
GMHC is an organization that helps address people living with HIV/AIDS, but when Gilead Sciences, one of the world’s largest manufacturers of AIDS medications, is donating hundreds of millions of dollars to AIDS and LGBT organizations, it creates conflicts of interest where the very AIDS organizations are actually benefiting from the drugs. So, you know, where’s the activism to push for an HIV/AIDS cure?
Alexey: It’s a vicious circle. For Gilead it’s profitable that people stay infected, but it’s not profitable for drug companies to be curing people.
Kambiz: It’s a lot like when tobacco manufacturers were selling their product knowing that it’s addictive, how the opioid manufacturers were selling their products really hooking everyone on it. I think it’s what’s going on with Gilead Sciences where that’s what’s happening with PrEP. All medications are helpful, but there are no silver bullets, and the way that PrEP has been rolled out introduces a lot of risks and a lot of questions with long-term ramifications.
Alexey: I feel like that’s also human nature – you just want to find an answer right away. You want a short solution to a problem. So I think this is where, probably, the pill culture in the US comes in, where it feels like there is a cure for almost everything.
Kambiz: There’s also so many factors and different views around health. What are the driving forces that people consider and weigh? I think one of the key drivers behind PrEP and using strong AIDS medications as a preventive is actually an emotional one. Some people who are HIV-positive don’t feel comfortable having sex with someone who’s HIV-negative because they don’t want to risk infecting them and vice versa. That’s because this is an infectious disease. It’s an infectious virus. There’s lots of ways to decrease that risk, including condoms, and taking a pill is one new way to do this. What’s beautiful about PrEP is, if you take this drug, it’s going to reduce infection rates.
It’s also a great tool in a monogamous relationship. For couples, where one person’s positive and one’s negative, the negative partner can choose to take PrEP to protect him or herself from acquiring the HIV infection.
When there’s so much emotion wrapped up in this space, PrEP also affects how people feel and handle obligations about disclosing their HIV status to sex partners. For instance I have one HIV-positive friend who says PrEP makes it easier for him to have sex. He thinks that because information about PrEP is sort of out there, that it’s up to everyone to protect themselves. So he sometimes feels he doesn’t need to disclose he’s positive. These are important ramifications to think about, too.
My problem with PrEP isn’t these current uses of it, but the longer-term considerations. What I’m thinking of specifically is the data that is just starting to come out. About half a year ago there was a case study in the Seattle area that showed six percent of people living with HIV/AIDS have HIV that has high-level resistance to Truvada. Six percent isn’t a small number. Yes, people who have HIV/AIDS should be taking medication so that they’re undetectable so they can’t pass it on.
But maybe they won’t, maybe they may miss a few doses, or maybe the medications stop working. It’s assuming a lot to think that the Truvada-resistant HIV in these six percent of people living with HIV/AIDS will always be under control. If you’re HIV-negative and you were to have sex with someone whose HIV has high-level resistance to Truvada, then even a bottle of Truvada won’t protect you from being infected. The six percent figure will only grow over time.
As HIV resistance to Truvada increases, there will be more and more PrEP failure. The solution in this case would be where pharmaceutical companies would ask us to take ever-stronger versions of PrEP medications:
Just like we have endless versions of iPhones, we will be asked to take PrEP version 10, PrEP version 11, and so on. I think what we’ve opened the door to is the idea that if you’re HIV-positive, take a pill. Oh, but now if you’re HIV-negative, also take a pill.
PrEP has opened a brand-new market for these drug companies. The new paradigm that we use strong powerful medications, even if we’re negative, is like brushing HIV under the rug. It is not a sound and long-term way to treat dangerous infectious diseases. If we overuse our drugs as a preventive method, then as the drug-resistant strains rise, we have to use stronger and stronger drugs to contain them – that’s the risk that I’m worried about.
I don’t think we’ve thought out the long-term ramifications of using PrEP. We are in a PrEP bubble, where right now it’s effective, but as the drug-resistant strains rise, and as we need stronger and stronger medications to protect us, is that really the world we want?
If we advance a cure and vaccine at the same time, then together with the pillar of PrEP and treatment and diagnosing people, we have a chance to really end it. But if we just put all our hopes on PrEP, I think we are opening the door to constantly ratcheting up the strength of the drugs that we’re going to expect generations of gay guys to take in the future.
Alexey: You’re 18 honey, it’s time for your PrEP. It’s a little bit insane and it’s actually a little bit scary when we talk about it that way, but it’s totally something that could be out of a Black Mirror episode.
Kambiz: Imagine there were no long-term risks, where we just pop these pills in order not to get HIV. Even then, I think we could do better than just have everyone be on a diet of drugs forever and ever.
That isn’t the dream. That’s not the goal. The goal should be to get rid of this thing, and we won’t get there if we just rely on these drugs. It’s a really delicate space. Very fascinating puzzle to solve.
Alexey: So let’s say tomorrow someone calls you and says
“I have a million dollars, here you go.”
How long do you think after that point it might take you to find a cure?
Kambiz: I think that we need about three to five years for the remaining preclinical work to get to the point of the cell therapy to start taking shape and then we can start clinical trials. So three to five years of work in the lab with scientists. And then you would have cell therapy enter human clinical studies, which would mean, you start your transition from working in the lab to going into a hospital and clinic with physicians and AIDS patients.
The clinical trial, I estimate, would be another three to five years. If we get the funding for the first step, a million dollars, that would be great, but we won’t be able to cure AIDS with a million dollars alone. But as we hit the goals of each stage, that would support getting the additional tranches of funding needed to advance it.
Alexey: I read that you want a cure to be cost-effective and practical. You want there to be a practical way to bring a cure to everyone around the world, right? So, how do you see that working in more rural parts of the world like, let’s say, in Africa?
Kambiz: It’s vital that an AIDS cure be not just for rich people in wealthy countries. I wouldn’t be putting in my time into anything if it was just for a few rich people – I think that it has to be available for everyone. I think that’s the challenge that drives me – how to create a cure that has a chance to benefit the lives of everyone who’s living with HIV/AIDS.
It’s scientifically thinkable, the first cures would be a little bit more involved. They would be more custom-made for each person. But once you create these custom cures for each person, because we’re talking about stem cells that are self-renewing, they grow and you can grow the curative cells for each person you treat in large vats and freeze them down for use with future patients.
So imagine you cured the first 2,000 patients or 10,000 patients. At some point we will get to a place where, let’s say, a patient number 10,001 shows up. It stands to reason that you could go into your frozen cell bank and pull out an ampule number 689 from that patient where you made it as a custom treatment, but now cells from this vial that are frozen down are suitable to pop into patient 10,001. So it could be that you create a repository of curative cells that you collected one by one by treating each patient. But you reach a point where you have this bank of curative cells that you can just pop into future patients. And that’s what will really make it broadly accessible.
Kambiz: I think what drives me is knowing it’s possible to cure this and figuring it out and not making money off of it. That’s what’s driving me, or I wouldn’t be doing it via a nonprofit. I think that’s how people should be doing things in general, like if there’s something you could add that can benefit others, put it out there and get collaboration and help from people with different expertise to make it real and tangible.
I believe in capitalism. I think it helps incentivize people, but I don’t believe that the system we have can’t be improved. I think when you’re talking about health and cell therapies and medicine, it’s not the same as washing machines or shoes. You can’t do those things fully for profit and, in my case, I invented something, started a biotech, the technology is multi-use, and we’re pursuing the other uses for profit. But in this case, it makes sense to me to do this via following a nonprofit model. HIV/AIDS affects a lot of people in countries where they can’t afford a cure. So, you have to do it with a nonprofit motive to make sure everyone’s included.
If you would like to donate, sign up for RFTCA’s newsletter, volunteer, or share your stories, you may do so here: rftca.org/GetInvolved/