November 2019
Examples of media coverage:
- Gene Tech Company Claims to Have Found a Cure for HIV/AIDS – NewNowNext, November 8, 2019
- Researchers believe they’ve found the cure for HIV/AIDS – Pink News, November 8, 2019
- Research Lab Believes They Have HIV/AIDS Cure – Instinct Magazine, November 7, 2019
- American Gene Technologies believes they have the cure for HIV/AIDS – LocalDVM.com, November 6, 2019
- Here’s Why the First Cure for HIV Could Emerge from Maryland – BioBuzz, November 6, 2019
Original source:
- American Gene Technologies Hosts Celebration Event For Its First IND Submission (For HIV) To The Food and Drug Administration (FDA) – American Gene Technologies Press Release, November 6, 2019
TAG’s commentary:
This sudden burst of misleading media coverage appears to trace back to two relatively low-profile local news stories from Maryland, USA, where the Biotech company American Gene Technologies is located.
The hyped-up headline of one of these stories (published by LocalDVM.com) was appropriated for a piece in Instinct Magazine that contains no context or analysis, and that led to a deluge of similarly shallow reporting.
The original local news stories were prompted by an event hosted by American Gene Technologies to celebrate submitting an Investigational New Drug (IND) application to the US Food and Drug Administration (FDA). The application seeks regulatory permission to conduct a phase I first-in-human clinical trial of an experimental gene therapy for HIV named AGT103-T. The submission was first announced last month.
The application is an important milestone for the company, but it does not mean that their gene therapy is a cure for HIV infection. There are as yet no results from either laboratory experiments or animal studies to support claims that it could have a curative effect.
Some of the news stories cite the 1,000+ page length of the IND application as if it’s evidence of the potential of the approach, but this is normal. For any new experimental candidate, the FDA requires the submission of extensive evidence about composition, safety and other issues in order to allow administration to a human.
While the media headlines about the potential of the gene therapy to cure HIV are misleading and extremely premature (at best), there are unique aspects to the American Gene Technologies approach that suggest it may hold promise and deserves testing in trials.
A considerable amount of prior gene therapy research in HIV has focused on protecting CD4 T cells from infection by the virus. HIV targets these cells, which are a critical component of the immune system. In the absence of treatment, loss of CD4 T cells due to HIV eventually leads to life-threatening immune deficiency.
A problem for gene therapies is that it is impossible to introduce protective genetic modifications into all the billions of CD4 T cells in a person’s body (at least with current technologies). The best-known HIV gene therapy approach, developed by the company Sangamo Therapeutics, was only able to modify a small proportion of the CD4 T cells in trial participants (the therapy aimed to knock out the CCR5 co-receptor that most HIV strains use to gain entry into CD4 T cells).
Results from Sangamo’s studies showed that some participants had significant increases in CD4 T cell counts, but when antiretroviral therapy (ART) was interrupted no consistent control of HIV viral load was observed. One participant has reported remaining off ART with a low viral load, but details are lacking, and this outcome was unusual.
The American Gene Technologies approach has similarities, but there is a twist. The company is focusing on trying to introduce protective genetic modifications into only the subset of CD4 T cells that are capable of recognizing and responding to HIV (called HIV-specific CD4 T cells).
Under normal circumstances, the CD4 T cells that specifically recognize and respond to a virus – such as influenza, for example – play a leading role in coordinating other components of the immune system to control viral replication and eliminate virus-infected cells. But HIV is known to preferentially infect HIV-specific CD4 T cells, leaving the immune system leaderless in its efforts to deal with the virus.
The goal of American Gene Technologies gene therapy is to create a population of HIV-specific CD4 T cells that is protected from HIV infection. A preparatory study that involves isolating HIV-specific CD4 T cells from people with HIV has been ongoing since July 2017.
The hope is that when ART is interrupted, the genetically modified HIV-specific CD4 T cells will be able to coordinate a strong immune response to the virus, leading to control of viral load without further treatment. Part of the rationale relates to observations that rare individuals who control HIV viral load without ART typically have strong and functional HIV-specific CD4 T cells.
As part of this effort, American Gene Technologies will collaborate with GeoVax, a company that manufactures an experimental therapeutic HIV vaccine. The aim is to try to boost the numbers of gene-modified HIV-specific CD4 T cells by administering the vaccine to study participants. If the trial receives the green light from the FDA and proceeds, it will represent the first time an HIV gene therapy has been combined with a therapeutic HIV vaccine.
While there is a good theoretical basis for pursuing this research, there is no direct evidence as yet that it will lead to a cure or even a temporary remission of HIV infection. Unfortunately, this major caveat is not conveyed by most of the current media coverage.
There are also a variety of possible reasons why the theory might not pan out. In order to have an effect, gene-modified HIV-specific CD4 T cells would likely need to recognize diverse HIV variants present in the person being treated. Furthermore, the process by which the immune system launches virus-specific CD4 T cells into action involves interactions with other immune cells that might be compromised by HIV, particularly dendritic cells. The location where these interactions take place – the lymphoid tissue, which acts as the immune system’s command center – can be scarred and damaged in people with long-term HIV infection (referred to as lymph node fibrosis).
The bottom line is that only clinical trials can answer the question of whether the American Gene Technologies gene therapy is capable of producing any beneficial effects in people with HIV. It’s encouraging that there is progress toward the first trial, and a collaborative agreement with researchers at the National Institute of Allergy and Infectious Diseases indicates that the approach is being taken seriously. But there is no way of knowing if it might lead to an HIV cure.