Gene therapy is one of the most exciting things happening in medicine right now, especially when it comes to curing HIV. Imagine this: scientists are developing ways to stop the virus from infecting your immune cells and even going as far as removing the virus’s genetic instructions from cells that are already infected. Crazy, right? But this isn’t just wishful thinking—it’s actually happening in clinical trials.



Two approaches are making waves. One focuses on protecting the immune system by making key cells resistant to HIV, while the other aims to cut the virus’s DNA right out of infected cells. It’s like giving your body a shield and a sword in the fight against HIV. These trials could change how we treat this virus forever, making daily medications a thing of the past.



In this article, you’ll find out how these treatments work, what makes them so groundbreaking, and where the research is headed.



## **What Is Gene Therapy and How Can It Cure HIV?**



Okay, let’s talk about gene therapy and why it’s such a game-changer for HIV. At its core, gene therapy is all about tweaking or modifying a person’s genes to fight or prevent disease. In the case of HIV, scientists are working on two groundbreaking ideas: one is to protect your immune cells so the virus can’t infect them, and the other is to hunt down and remove the virus’s genetic instructions from the cells it’s already infected.



Here’s the thing: HIV is incredibly tricky. It hides in your immune system’s CD4 cells—these are like the command center for fighting off infections. Even if you’re on antiretroviral therapy (ART) and the virus seems under control, its DNA is still lying dormant, ready to wake up if you stop taking your meds. This is why curing HIV has always been so difficult.



Gene therapy tackles this challenge in ways that were unimaginable just a few years ago. For example, one approach involves editing a gene called CCR5. Think of CCR5 as the doorknob that HIV uses to get into your cells. Scientists can disable this “doorknob,” making it impossible for the virus to enter. Another method uses a technology called CRISPR, which acts like tiny molecular scissors. It can search for HIV’s DNA inside infected cells and cut it out.



What’s exciting is that these aren’t just ideas on paper—they’re being tested in real clinical trials, and the results so far are really encouraging. The ultimate goal? To give people living with HIV the chance to stop daily medications and live without fear of the virus bouncing back.



## **How Does AGT103-T Protect CD4 Cells From HIV?**



Alright, let’s dive into AGT103-T and what makes it such a fascinating approach to tackling HIV. AGT103-T is part of a clinical trial by American Gene Technologies (AGT), and it’s designed to do something revolutionary—make your CD4 cells, the very cells HIV attacks, completely resistant to the virus.



Here’s how it works: First, scientists take a sample of your blood and isolate CD4 cells that specifically recognize parts of the HIV virus, like its Gag protein. These are the cells that are already trying to fight the virus. Once they’ve got these cells, they genetically modify them in the lab.



The key here is disabling something called the CCR5 receptor. Think of CCR5 as the doorway that HIV uses to enter your cells. By editing the genes of your CD4 cells to remove CCR5, they essentially lock the door, so the virus can’t get in. The scientists use a harmless virus (a lentivirus vector) to deliver these genetic changes, which makes the process precise and safe.



Once the CD4 cells are modified, they’re grown in large numbers in the lab to create an army of HIV-resistant cells. These cells are then infused back into your body, where they’re expected to multiply and replace the vulnerable CD4 cells that HIV can attack.



Why is this approach so promising? We already know from real-life cases that people who naturally lack the CCR5 receptor—due to a rare genetic mutation called CCR5-delta32—are almost completely resistant to HIV. Two people, famously known as the “Berlin Patient” and the “London Patient,” were cured of HIV after receiving stem cell transplants from donors with this mutation. AGT103-T aims to replicate this same effect without the risks of a dangerous stem cell transplant.



Early results from the AGT103-T trial are encouraging. Participants have shown no major side effects so far, and researchers are moving forward cautiously but with real optimism. The big test will come when participants stop taking their antiretroviral medications to see if the virus comes back. If it doesn’t, this could be a major step toward a functional cure for HIV.



## **What Are the Preliminary Results of the AGT103-T Trial?**



Now, let’s talk about what the early results from the AGT103-T trial are showing us. So far, things are looking promising. AGT103-T is being tested in a Phase 1 clinical trial to see if it’s safe and effective at improving the immune system’s ability to fight HIV. This trial has included participants who have been living with HIV for years and are currently on antiretroviral therapy (ART).



The therapy works by infusing genetically modified CD4 cells back into the body, but what’s really exciting is how these modified cells are performing. According to a recent study, participants received either a low or high dose of AGT103-T (anywhere from 2 to 21 million genetically modified cells per kilogram of body weight). Importantly, there were no serious adverse events (SAEs), and all observed side effects were mild. This is a big deal because it shows the treatment is safe.



Even more impressive is how these cells are boosting the immune response. After the infusion, the levels of Gag-specific CD4 T cells—cells that specifically target parts of the HIV virus—shot up significantly. In fact, they increased by 9 to 300 times their baseline levels just 14 days after treatment. These higher levels persisted for months, staying 2 to 70 times higher than baseline even six months after the infusion.



The treatment didn’t just boost CD4 cells—it also increased Gag-specific CD8 T cells, another critical component of the immune response. By 28 days after treatment, these cells were 1.7 to 10 times higher than baseline levels. Essentially, AGT103-T seems to be giving the immune system a serious upgrade, helping it target HIV more effectively.



Researchers also noted that the genetically modified cells were still detectable in participants’ blood six months after the infusion. This means the treatment appears durable, which is another critical marker for success.



While these results are incredibly encouraging, the next big step is to see what happens when participants stop taking ART. If AGT103-T can prevent the virus from rebounding without daily medications, it could represent a major leap forward in the search for a functional cure.



## **How Does Excision BioTherapeutics’ EBT-101 Target HIV DNA?**



Let’s talk about Excision BioTherapeutics and their bold approach to tackling HIV. Unlike AGT103-T, which focuses on protecting immune cells from infection, EBT-101 takes a different path. It aims to hunt down the virus’s DNA in already infected cells and cut it out—literally removing the virus’s instructions from your body.



Here’s how it works: EBT-101 uses a cutting-edge technology called CRISPR, which you might have heard of as a kind of “gene-editing tool.” Think of CRISPR like molecular scissors. It’s designed to find HIV’s DNA hiding in your CD4 cells and make precise cuts to disable it.



The process starts with RNA templates, which act like guides, leading the CRISPR system to the exact spots in the cell’s DNA where HIV has integrated itself. Once CRISPR locates the HIV DNA, it uses an enzyme, called a nuclease, to make multiple cuts. This is important because if you only make a single cut, the virus can mutate and repair itself. By targeting multiple sites, EBT-101 ensures that the virus’s genetic blueprint is completely disrupted. After the cuts are made, the cell’s natural repair mechanisms step in to rejoin the ends of the DNA, effectively removing the sections of the genome that allow HIV to replicate.



Why is this approach such a big deal? Current HIV treatments focus on suppressing the virus, but they don’t touch the latent reservoirs of HIV DNA hiding in your cells. EBT-101’s goal is to clear out these reservoirs, stopping the virus from reactivating even if you stop taking your medications.



Preclinical studies in the lab and in animal models have shown that EBT-101 can successfully remove pieces of HIV DNA and reduce viral replication. Now, for the first time, the technology is being tested in humans. Participants in the trial receive a single IV infusion of EBT-101. After three months, they undergo a carefully monitored antiretroviral treatment interruption to see if the virus stays suppressed without medication.



The idea here isn’t necessarily to completely eradicate the virus—that would be a “sterilizing cure,” and it’s extremely difficult to achieve. Instead, the goal is a “functional cure,” where the virus is so suppressed that it can’t cause harm, and patients can live HIV-free without daily treatment.



Excision BioTherapeutics has just entered the early stages of human trials, so it’ll be some time before we know how well this works. But the potential here is enormous. If successful, EBT-101 could pave the way for entirely new strategies for curing HIV.



## **What Are the Next Steps for EBT-101?**



Now that Excision BioTherapeutics has taken the first steps with EBT-101, let’s talk about what comes next. The current clinical trial is a Phase I/II study, which means the researchers are focusing on two main things: safety and early signs of effectiveness.



Participants in this trial receive a single IV infusion of EBT-101, and then their progress is carefully monitored over several months. The first big milestone comes three months after the infusion when the participants stop taking their antiretroviral therapy (ART). This is a crucial moment because it will show whether EBT-101 can suppress the virus without the need for daily medications.



The researchers are looking for signs that the virus doesn’t rebound—that is, the participants’ viral load stays low or undetectable even after stopping ART. They’ll also track whether the modified cells remain in the body and continue to function as intended. This is where the concept of a “functional cure” comes in: the goal is to keep the virus under control so it doesn’t cause harm or spread, even if some dormant viral DNA remains in the body.



Another important step involves monitoring for safety. Since EBT-101 uses CRISPR, a very precise gene-editing tool, researchers are making sure there are no off-target effects—meaning, no unintended changes to other parts of the participants’ DNA. So far, the technology has shown a good safety profile in preclinical studies, but this trial will confirm how it performs in humans.



Excision BioTherapeutics is also planning to expand the trial if early results are promising. This means enrolling more participants and possibly testing the treatment in different groups, such as people who have been living with HIV for a long time or those with more complex medical histories.



## **What Are the Key Differences Between AGT103-T and EBT-101?**



Both AGT103-T and EBT-101 are groundbreaking approaches to tackling HIV, but they work in completely different ways. Let me explain how these two strategies compare.

### **Mechanism of Action**



AGT103-T focuses on protecting CD4 cells from getting infected in the first place. It does this by genetically modifying these cells to make them resistant to HIV. The key here is disabling the CCR5 receptor, which HIV uses to enter the cells. By locking this “door,” AGT103-T creates a barrier that prevents the virus from spreading in the body.



On the other hand, EBT-101 doesn’t try to protect cells—it goes after the virus that’s already hiding in them. Using CRISPR technology, EBT-101 cuts out pieces of HIV’s DNA from infected cells. This directly disrupts the virus’s ability to replicate and produce more virus particles.

### **Goal of Treatment**



AGT103-T aims to replace vulnerable CD4 cells with HIV-resistant ones, effectively building a fortified immune system. It’s like giving your body an upgraded army to fight HIV.



EBT-101, however, is about reducing or eliminating the viral reservoir. The viral reservoir is where HIV hides in a dormant state, making it impossible to cure with current treatments. EBT-101’s goal is to “cut out” these hidden instructions so the virus can’t come back.



### **Administration Method**



AGT103-T is a cell therapy. This means scientists take a sample of your blood, modify the CD4 cells in a lab, and then infuse them back into your body.



EBT-101 is a simpler process in terms of delivery—it’s a one-time intravenous (IV) infusion. The CRISPR system is delivered directly into your body to find and edit the infected cells.



### **Trial Focus and Progress**



AGT103-T is currently being tested in a Phase I trial with a small group of participants. The early results have shown that the treatment is safe and well-tolerated, and the big test will come when participants stop their antiretroviral therapy.



EBT-101 is also in early clinical trials, but its focus is more on ensuring the CRISPR editing works as intended and doesn’t cause any unintended changes to other parts of the participants’ DNA.



### **End Goal: Functional Cure vs. Sterilizing Cure**



Both approaches aim for what’s called a “functional cure.” This means the virus is controlled without daily medications, but some dormant viral DNA may still remain. Neither approach is currently aiming for a “sterilizing cure,” which would mean removing every single trace of HIV from the body.



In short, AGT103-T acts as a shield, protecting the body from future HIV attacks, while EBT-101 acts as a sword, targeting and removing the virus’s instructions. Both are incredibly innovative, representing two promising paths toward changing how we treat HIV.



## **Conclusion**



So, there you have it—two cutting-edge approaches that could change the game for people living with HIV. AGT103-T is all about building a strong defense by making your immune cells resistant to the virus, while EBT-101 goes on the offense, of cutting out the virus’s DNA from infected cells. Both methods are still in the early stages, but they’re giving us something we haven’t had in a long time: hope for a future where living with HIV doesn’t mean a lifetime of daily medications.



## **Sources**



Pharmaceutical Technology. (n.d.). AGT103-T (Addimmune) for Human Immunodeficiency Virus (HIV) Infections (AIDS) – Likelihood of Approval. Retrieved from [https://www.pharmaceutical-technology.com/data-insights/agt103-t-addimmune-human-immunodeficiency-virus-hiv-infections-aids-likelihood-of-approval/](https://www.pharmaceutical-technology.com/data-insights/agt103-t-addimmune-human-immunodeficiency-virus-hiv-infections-aids-likelihood-of-approval/)



European AIDS Treatment Group. (n.d.). Researchers Test Two Gene Therapy Approaches for Curing HIV. Retrieved from [https://www.eatg.org/hiv-news/researchers-test-two-gene-therapy-approaches-for-curing-hiv/](https://www.eatg.org/hiv-news/researchers-test-two-gene-therapy-approaches-for-curing-hiv/)



Muvarak, N., Li, H., Lahusen, T., Galvin, J. A., Kumar, P. N., Pauza, C. D., & Bordon, J. (2022). Safety and durability of AGT103-T autologous T cell therapy for HIV infection in a Phase 1 trial. PubMed. Retrieved from [https://pubmed.ncbi.nlm.nih.gov/36452901/](https://pubmed.ncbi.nlm.nih.gov/36452901/)

<p>Discover if AGT103-T and EBT-101 gene therapies can cure HIV by protecting immune cells and eliminating HIV DNA. Learn these innovative treatments!</p>

HIV Treatment: AGT103-T & EBT-101 Gene Therapies

Can AGT103-T and EBT-101 gene therapies lead to an HIV cure? Learn how these innovative treatments aim to protect immune cells and remove HIV DNA.

Revolutionizing HIV Treatment: AGT103-T and EBT-101 Gene Therapies

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