Funding a Clinical Trial for a Functional Cure for HIV

The use of antiretroviral drugs has turned HIV/AIDS from a fatal disease to one that can, in many cases in the US, be controlled. But these drugs are not a cure. That’s why the governing Board of the California Institute for Regenerative Medicine (CIRM) voted to approve investing $6.85 million in a therapy that aims to cure the disease.

This is the 82nd clinical trial funded by CIRM.

There are approximately 38 million people worldwide living with HIV/AIDS. And each year there are an estimated 1.5 million new cases. The vast majority of those living with HIV do not have access to the life-saving antiretroviral medications that can keep the virus under control. People who do have access to the medications face long-term complications from them including heart disease, bone, liver and kidney problems, and changes in metabolism.

The antiretroviral medications are effective at reducing the viral load in people with HIV, but they don’t eliminate it. That’s because the virus that causes AIDS can integrate its DNA into long-living cells in the body and remain dormant. When people stop taking their medications the virus is able to rekindle and spread throughout the body.

Dr. William Kennedy and the team at Excision Bio Therapeutics have developed a therapeutic candidate called EBT-101. This is the first clinical study using the CRISPR-based platform for genome editing and excision of the latent form of HIV-1, the most common form of the virus that causes AIDS in the US and Europe. The goal is to eliminate or sufficiently reduce the hidden reservoirs of virus in the body to the point where the individual is effectively cured.

“To date only a handful of people have been cured of HIV/AIDS, so this proposal of using gene editing to eliminate the virus could be transformative,” says Dr. Maria Millan, President and CEO of CIRM. “In California alone there are almost 140,000 people living with HIV. HIV infection continues to disproportionately impact marginalized populations, many of whom are unable to access the medications that keep the virus under control. A functional cure for HIV would have an enormous impact on these communities, and others around the world.”

In a news release announcing they had dosed the first patient, Daniel Dornbusch, CEO of Excision, called it a landmark moment. “It is the first time a CRISPR-based therapy targeting an infectious disease has been administered to a patient and is expected to enable the first ever clinical assessment of a multiplexed, in vivo gene editing approach. We were able to reach this watershed moment thanks to years of innovative work by leading scientists and physicians, to whom we are immensely grateful. With this achievement, Excision has taken a major step forward in developing a one-time treatment that could transform the HIV pandemic by freeing affected people from life-long disease management and the stigma of disease.”

The Excision Bio Therapeutics team also scored high on their plan for Diversity, Equity and Inclusion. Reviewers praised them for adding on a partnering organization to provide commitments to serve underserved populations, and to engaging a community advisory board to help guide their patient recruitment.

CIRM has already invested almost $81 million in 20 projects targeting HIV/AIDS, including four clinical trials.

HIV eliminated from mice using CRISPR and LASER ART

Dr. Kamel Khalili

In the United States alone, there are approximately 1.1 million people living with Human immunodeficiency virus (HIV), a virus that weakens the immune system by destroying important cells that fight off disease and infection. This number is much larger on a global scale, with 36.9 million people living with HIV as of 2017. If left untreated, the immune system becomes so weakened that the condition worsens into acquired immunodeficiency syndrome (AIDS), which is usually fatal.

Current treatment for HIV focuses on the use of antiretroviral therapy (ART). This treatment is able to suppress replication of the virus, but it does not eliminate it from the body entirely. In order to be sustainable, ART must be taken throughout the course of a lifetime, otherwise HIV rebounds and the replication of the virus renews, fueling the development of AIDS.

The ability of HIV to rebound is related to the fact that it is able to integrate its DNA into various cells inside the body and beyond the reach of ART. Here they are able to remain dormant and ready to replicate as soon as ART is not interfering. It is because of this that ART is not sufficient on its own to cure HIV, but a group of scientists have uncovered a promising breakthrough to change that.

In a major collaboration, researchers at the Lewis Katz School of Medicine at Temple University and the University of Nebraska Medical Center (UNMC) have for the first time eliminated HIV from the DNA of living mice. This study marks a critical step toward the development of a possible cure for human HIV infection.

The team of researchers was able to do this with the help of a new technology called long-acting slow-effective release (LASER) ART. LASER ART is able to target HIV sanctuaries and maintain replication at low levels for extended periods of time. Immediately after administering LASER ART, the team used a gene editing technology known as CRISPR to remove the final remnants of HIV DNA hidden inside cells.

In a press release, Dr. Kamel Khalili, senior investigator for this study, was quoted as saying,

“Our study shows that treatment to suppress HIV replication and gene editing therapy, when given sequentially, can eliminate HIV from cells and organs of infected animals…We now have a clear path to move ahead to trials in non-human primates and possibly clinical trials in human patients within the year.”

The full results of this study were published in Nature Communications.

To learn more about how CRISPR technology works, you can read more about it on a previous blog post.