A “functional cure” for “HIV”?

A look at the biotech startup “Addimmune”

Recently, there have been a few stories about potential “cures for ‘HIV’.” We covered one in March in this post. The technology mentioned in that story involved CRISPR gene therapy, and its results were underwhelming.

However, there is another potential “cure for ‘HIV’” on the horizon, and it involves introducing “modifying miRNAs to patients’ CD4 T cells.” This new technology is sponsored by a company named Addimmune. The following video is an interview with Addimmune’s founder and CEO, Jeff Galvin with a YouTube creator named Raif Derazzi. I’ll make very few comments about the video itself, because I will also be reacting to an article about Mr. Galvin and his mission in Bioprocess Online.

I will point out that this video ends with a plea for money. I notice also that Mr. Galvin seems to be trying very hard to appear to be “alternative” and skeptical of Big Pharma. He claims that people thought he was crazy when he started this research, but that “sometimes it is the crazy people that change the world.” I don’t know enough about the man to guess whether this is sincere. One point I want to make that the article doesn’t mention until close to the end is that his Phase I (safety) trial—the only Addimmune trial undertaken and completed to date—enrolled seven patients. This entire video discusses the results of a seven person trial, which ran from 2020 to 2021. (He also defines “undetectable” as either below 20 or below 50 copies per mL—which is it?)

Let’s dive into the article and see if there’s a there there. This article appeared in February 2024.

1 In 300 People In The U.S. Is Living With HIV. That's Not Okay With Jeff Galvin.

Here’s the pull quote:

By modifying CD4 T cells using miRNA, Jeff Galvin’s company thinks it can deliver a functional cure for HIV. Here’s the ongoing story of Addimmune and its unique clinical strategy.

What is miRNA, you might ask? It’s not the same as mRNA (the extra letter is a clue); according to Science Direct, “microRNA (miRNA) are noncoding RNAs ranging from 18 to 20 nucleotides that regulate diverse cellular processes ranging from apoptosis, proliferation, and differentiation to metastasis.” (Emphasis in the original.) So basically this is “viral vector” technology.

The article begins with a recitation of how distressing the “persistence” of “HIV” in the population is. I agree that it is certainly interesting that “HIV” has persisted at a basically constant level in the population for forty years. Explain again how this represents the transmission pathway of an infectious disease. Regardless, I’d like to focus on Addimmune and their biologic strategy here. All emphasis is mine moving forward.

The disease’s persistence isn’t the only thing that irks Galvin. Despite its statistical progress, he calls the standard of care a healthcare policy nightmare. He points to the multi-million-dollar lifetime cost of care per patient that rolls up to a hundred-billion-dollar burden on patients and payers. A lack of adherence to an aggressive and expensive HIV treatment regimen, he says, puts patients and their partners at risk. Current treatments require daily oral administration, or in some cases, injections of time-release antiretrovirals every other month, for life.

That bolded sentence is quite something. I agree with Mr. Galvin that the standard of “retention in care” is indeed a nightmare. But what is this “statistical progress” he refers to? I assume it means the success of “retaining in care” as many patients as possible.

Mr. Galvin’s background is interesting, as well.

Galvin’s passion for addressing the HIV problem is palpable, but what fuels it is up for debate. Solving biology problems isn’t what he trained for. He’s a Harvard economics grad who walked that degree into Hewlett Packard in 1981. From HP it was on to Apple, then Blyth Software, then Claris Software, then Argus Software.

[…]

A particular pitch from the NIH caught his eye. He followed up, and the next thing he knew, he was face-to-face with Roscoe Brady, M.D.

[…]

“Roscoe Brady showed me viral vectors, and my head just exploded,” Galvin recalls. “I said, ‘wait a minute. You just showed me the diskette for the organic computer of the human cell.’”

It’s no surprise that where Brady saw cells and viruses, Galvin saw data and code. Long before he worked as a software engineer at HP, before he led international product marketing efforts for Apple, and before he earned that Harvard economics degree, way back when he was a teenager, Galvin taught computer classes at Harvard. His computationally-gifted-since-childhood mind asked, “if we can reprogram DNA, what can’t we cure?”

How intriguing is it that the entire AIDS establishment has spent forty years failing to find a cure or a vaccine for “HIV,” yet the best hope being offered is by treating the human body like a computer? I’m sure there are many people that would consider this overwhelmingly positive, but I’m somewhat skeptical, given the move toward modeling illness and treatment “in silico.” Instead of Big Pharma, it’s morphed into Pharma Tech (not to be confused with the actual company or companies; I mean Pharma Tech as a concept.) Let’s move on to what Addimmune’s protocol actually is.

With his newfound optimism that viral vectors could be programmed like software to potentially cure anything, Galvin founded American Gene Technologies (AGT) in 2008. The company set out to build a development platform that could address immuno-oncology, monogenic disease, and HIV.

[…]

“We’re modifying genes that have very specific outcomes in cells,” Galvin explained “Cells work in a very deterministic manner in terms of what they do internally, and DNA is the operating system of the cell. Each gene serves as the command that results in that very specific outcome, and if you trigger that command, you can direct and predict the outcome.”

This is all very dehumanizing. It’s a completely materialistic view of humanity and of life in general. And it isn’t even clear as to how well this approach will work.

The computational analogy doesn’t stop there. The 37 trillion cells, give or take, in the human body are connected by an electrical, chemical, and physical infrastructure that Galvin compares to a computer network. The pathogens that cause disease? Those he equates to “bugs,” those pesky bits of foreign code that infect computer operating systems. In the human operating system, he says Addimmune (the HIV-related portion of AGT’s business) can crack open the viruses that carry these bugs and scoop out the bugged software, that bit of DNA or RNA that hijacks cells and causes disease. “Now that it’s hollowed out, it’s an empty diskette that can deliver anything to any cell,” he says. “When we put something good in there, we’re converting viruses into updates for the organic computer.”

Here is the last piece of background about Galvin and Addimmune; after that we will focus on the actual technology used in his trial.

By 2023, Galvin’s vision of human biology as an organic computer had produced 47 patents that relate to the company’s viral vector development platform. While he doesn’t bite on the platform-versus-product value debate that’s so trendy to tussle over (“what’s more important,” he asks rhetorically, “the iPhone or the app?”), that was the year Galvin recognized that American Gene Technologies was no longer just a platform company. It was ready to spin off a biotech. That’s when Addimmune, a company that lives by the ‘body as an organic computer’ mantra Galvin evangelizes, was born. Where Addimmune would focus its therapeutic endeavors was influenced, as are the launch of so many biotechs, by serendipity.

“Our decision to focus on HIV as the proof point for our approach was blessed,” says Galvin. “We’re headquartered just south of the Institute of Human Virology (IHV). We had access to some top researchers up there to review and replicate our initial experiments.”

The Institute of Human Virology, or IHV (cute how it’s an anagram of “HIV”) is Bob Gallo’s baby. Serendipitous, indeed. So how does Addimmune’s technology work?

The HIV virus infects and kills sentinel T cells (CD4 T cells) that are there to detect it and elicit an immune response. Once CD4 T cells are depleted, HIV patients acquire an immune deficiency to the AIDS-causing pathogen. AGT103-T, Addimmune’s phase 1B lead candidate, delivers modifying miRNAs to patients’ CD4 T cells. Those miRNAs knock out the CCR5 receptor, the point of HIV’s attack. If the cell is already infected with HIV, additional miRNAs in AGT103-T target highly-conserved sites in the HIV genome to help stop further replication of the virus. The company believes the approach will help CD4 T cells become resistant to HIV’s entry and propagation of infection by enabling an effective immune response.

Once CD4 T cells are depleted, patients acquire an immune deficiency to “HIV?” This is news to me; the entire paradigm model states that “HIV” infects these cells and causes their depletion, by some still mysterious mechanism, and despite a robust antibody response. I’m sure this is just sloppy writing, but it’s a significant error. What causes the T cell depletion if the T cell depletion causes the “immune deficiency?”

Targeting the “CCR5 receptor” is not new in “HIV” research; medical researchers have been intrigued by the possibility of eliminating “HIV” using related mechanisms for years, to no avail.

“In our initial Phase 1 safety studies, we introduced a target quantity of a billion of these cells to patients and observed them while the patients stayed on their antiretroviral therapies for a minimum of 180 days, to determine whether we could introduce a billion cells without making patients sick,” explains Galvin. “There were no serious adverse events in the study, so we met our safety endpoint.” [Remember this study enrolled seven patients.—Ed.]

[…]

Of course, observation of those patients over 6 months revealed a gradual, though expected, depletion of CD4 T cells. That’s the normal immune response as those cells deplete to memory levels capable of supporting their ability to come back to the fight when called on. The next series of studies were intended to address whether these modified CD4 T cell memory levels would support a patient’s ability to fight HIV without antivirals.

Six out of seven patients agreed to an analytic treatment interruption, meaning they’d go off their antiretrovirals, allowing the virus to emerge from their viral reservoirs, to determine whether their immune systems responded to the appearance of the virus. Galvin says all six patients demonstrated an immune response, indicating that the CD4 T cells seemed to be surviving the HIV viral attack and could persist in doing their job.

In that study, there was a “but.” Viremia, the presence of the virus in those patients’ blood, didn’t cap at a level that Addimmune felt safe to remain off antiretroviral treatment. The patients were put back on their antiretrovirals to bring their viremia back to “undetectable” levels.

So if I’m understanding this correctly, they introduced these miRNA modified cells into patients by the billions, with no adverse events among seven people in 180 days. Six of the seven agreed to a “drug holiday,” after which their “viremia” (a misleading term because they really mean “viral load,” which is not viremia) rebounded. Regardless, four of the seven agreed to a second “drug holiday.” We’re already down to slightly more than half.

Once patients’ viremia levels dropped to a controlled level, Addimmune asked them if they’d be willing to go back off their antiretrovirals a second time. Four of the six patients agreed. All four saw a reduction in viremia, two of them maintaining approximately 5,000 to 10,000 particles per milliliter for approximately four months. The 5,000 to 10,000 per milliliter concentration is considered a long-term non-progression level without antiretrovirals, and it’s something only .5 percent of HIV patients experience without treatment.

I’m a little confused by this. Did they see a reduction in viremia after going off ARVs, or was it after ending their treatment interruption, as was the case with the first group whose treatment was interrupted? This must have been during their drug holiday, as they weren’t “undetectable,” but how interesting that “long term nonprogression” (which allegedly means you won’t develop AIDS) is defined not by being undetectable, but by having a “viral load” of less than 10,000.

Galvin states also that his goal is to “allow the immune system to tamp down the virus so low that it’s non-transmissible.” In the video, he talks a good talk about how much money Big Pharma makes on these lifelong patients, trying to sound like some kind of renegade, while out of the other side of his mouth he states (in the video) that “Cell therapy would earn pharma companies more money than the current model.” He then ends the video with an appeal for donations to Addimmune. Also, he makes a very interesting statement. He claims that the current cost of “treating ‘HIV’” is in treating the side effects. I thought he meant the side effects of the medication but no—“They’re not having the side effects of liver and kidney problems because they’re on treatment.” Does he really not know that ARVs CAUSE liver and kidney problems? Why does he think—and I know he knows it—these patients have to have those levels monitored while on treatment for precisely the reason than they harm the liver and kidneys?

We’re almost done (thank God). What’s next for Addimmune, after their incredible results that they saw in four out of seven patients?

While it’s a bit short of the goal line, Addimmune has downs left to play. Its next step is to run the same offensive scheme it did last time, but with a few twists. The company is recruiting 24 new patients for a 3-arm study in which those patients will be given the target dose of its miRNA therapeutic (with slightly different attributes or parameters in each arm of the study), then taken off of their antiretrovirals shortly after the infusion. At a minimum, the company hopes to recreate or improve on the long-term non-progression levels it’s already seen.

The writer is already hedging his bets; the very next paragraph basically assumes this isn’t going to work.

Should it fall short of its goal to deliver a functional cure on this series of downs, Addimmune still has a potentially viable product. A dramatic improvement to long-term non-progression status would be a win.

What’s with the constant football references? Finally, Galvin and Addimmune have set their sights far beyond “HIV:”

Galvin says cancer and monogenic disease targets remain a focus of the platform that shares its foundation with the HIV cure attempt. “Our HIV program could be a proof of concept that we can create powerful gene and cell therapy drugs for other diseases better, faster, and potentially cheaper than other companies,” he says, “And our parallel to the software development industry hasn’t broken down yet. That said, we acknowledge that the human body is way more complex. The organic computer has an amazing command set, but it didn’t come with a manual.”

I agree that the technology is quite dazzling, but I fear this is heading in a very dangerous direction. We already have seen serious adverse effects from the gene therapy known as the “COVID vaccines;” furthermore, this represents yet another step away from a holistic consideration of health and toward an entirely materialistic view of human beings. Not only that, but this therapy has only been tested on a tiny handful of people, with less than perfect results. After so many years of failure, does the hope of “ending ‘HIV’” rest entirely on a model of the human body as a computer?

What do you think? Is this legitimate, or a giant money grab? I will point out one last thing before closing, and that is that in the video, Galvin points out (referring to Big Pharma, of which PharmaTech is arguably a part) that “the desperate are easy to take advantage of.” I don’t think I need to say any more. Let me know what you think in the comments.

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If you’re a new reader and would like some background as to my views on HIV AIDS, including the “existence” question, please refer to this post and the links contained therein. My interview with Sam Bailey is also a great introduction.