Forty years after the start of the HIV/AIDS epidemic in the United States, more than 1.2 million people are living with HIV in the country and there are more than 35,000 new infections each year. As of December 2019, the number of people in North Carolina living with the virus was 38,400 and in South Carolina was 20,334.
Antiretroviral treatment, often known as ART, has drastically impacted treatment over the past decade, meaning that people with HIV can live long and healthy lives. While not a cure, ART keeps HIV under control and reduces a person’s viral load to an undetectable level. This means that people with HIV who are undergoing antiretroviral treatment have effectively no risk of transmitting HIV to their HIV-negative partners through sex.
It does not eliminate HIV completely, however, but recent news of a possible cure have many in the community hopeful. In a statement on June 5, President Joe Biden said “Thanks to the tireless dedication of activists, scientific researchers and medical professionals, we have made tremendous progress to advance HIV research, prevention, treatment and care.”
The U.S. has invested more than $85 billion since 2002 to support HIV programs around the world, including $250 million provided in the American Rescue Plan to address the impacts of COVID-19 on progress to fight against HIV.
Now, the U.S. Food and Drug Administration (FDA) has given clearance for human trials of a “functional cure” of HIV. The CRISPR-based therapy, developed by Excision BioTherapeutics, Inc. is a unique gene therapy and is intended to treat individuals living with chronic HIV who are currently using ART.
According to a press release, the clearance enables Excision to initiate a first-in-human Phase 1/2 clinical trial to evaluate the safety, tolerability and efficacy of EBT-101 in people living with HIV. “Although antiviral treatments can manage HIV infection, they require life-long treatment, cause side effects, and do not provide the possibility of a functional cure,” said Daniel Dornbusch, CEO of Excision.
Researchers at Temple University are in partnership with Excision to proceed with the clinical trials and commercialize treatments. Excision secured $60 million in investor financing in February and in August, Temple received a grant from NIH that will provide the team with $4.8 million each year for five years to support the team’s “CRISPR for Cure” project.
CRISPR gene-editing technology is designed to target and eliminate HIV from infected cells.
What is a “functional cure?”
According to Elizabeth Boskey, PhD, “When most people talk about a cure for HIV, they generally imagine a drug or vaccine that would remove all traces of the virus from the body (referred to as a sterilizing cure).” Boskey is a social worker and adjunct lecturer at Boston University.
Such a cure is highly unlikely for HIV.
HIV quickly infects human T-cells, an important component of the immune system. The virus embeds itself into cells and tissues throughout the body, creating what’s called a viral reservoir. That reservoir is the greatest obstacle to an HIV cure, according to the National Institute of Allergy and Infectious Diseases (NIAID).
These latently infected cells are invisible to the body’s immune system. If a person stops treatment, virus from the reservoir starts replicating again. Stem-cell transplantation, like that of the “Berlin Patient” have resulted in positive results, but the NIAID points how that the risk, difficulty and expense of such treatments make this a highly impractical approach to curing HIV in most people.
“A functional cure would not eradicate the virus but rather enable the body to stop HIV from proliferating without the need for further treatment,” states Boskey.
Excision’s EBT-101 has been tested in nonhuman primates, which showed it reached every tissue in the body where HIV reservoirs reside. The biotech plans to initiate a its clinical trial later this year, according to the press statement.
American Gene Technologies in Rockville, Md. is currently in Phase 1 human trials for a single dose, autologous cell therapy intended to cure HIV. The treatment is also a functional cure.
In a statement from September, the biotech announced that the independent Data Safety and Monitoring Board found no serious adverse events from the treatment of a second patient and voted to allow AGT’s HIV cure program to continue without modification.
“We’re putting viruses into their bodies that are going to specific cells and that are making very, very specific changes in a targeted way,” said Jeff Gavin, CEO of AGT in an interview with WUSA-9 in Washington, D.C.
Gavin explained that the process included taking blood from a man with HIV to get to his infected T-cells They then modified the T-cells to make them resistant and put them back into the patient. If all goes as planned, this should keep the virus from spreading.
“We have learned so much about viruses, specifically about HIV, that we can now crack them open, scoop out their disease software,” Gavin said in the interview. “The HIV community has been waiting for a cure for so long.”
At the Sanford Burnham Prebys (SBP) Medical Discovery Institute in California, researchers are trying a “shock and kill” approach. In a recent online panel discussion, Lars Pache, Ph.D. said that a treatment that awakens the virus might help actually eliminate it.
“It may sound counterintuitive that you want to activate the virus if you’re actually trying to combat it,” says Pache. “It may sound dangerous. However, you need to consider that anyone who would undergo a treatment like this is also on therapy with antiretroviral drugs, meaning that even if these cells are reawakened – that the virus is reawakened – due to the antiretroviral drugs, this virus cannot spread. It cannot infect any cells. The only thing that happens is that these cells become visible for destruction.”
Pache is the Research Assistant Professor for the Immunity and Pathogenesis Program at SBP’s Infectious and Inflammatory Diseases Center.
The group’s new drug, Ciapavir, reactivates dormant HIV cells, making them a target for elimination. The team has completed preclinical studies and will now move forward into the safety and formulation stage before filing with the FDA for approval.
This stage includes determining appropriate human dose and dosing strategies, identifying any potential liabilities or side effects and refining the drug for safety and tolerability in humans.
Max Disposti is the founder and executive director of North County LGBTQ Resource Center, just a two hour drive from SBP’s research facility and brought together Pache, along with Raphael Rubalcaba, an HIV supportive services specialist with Advantage Healthcare Services and Allison Limpert, Ph.D., a scientist in cell and molecular biology at SBP for a discussion in May.
Disposti understands why such news is important for the LGBTQ community, especially those in rural areas. “Not everyone in the U.S. has the ability to have specialized providers that are at the forefront of medication,” he said. “Many people who live in rural areas, where a diagnosis of HIV could be really devastating, and now you become the disease – you’re not a person with HIV, now you become an HIV person.”
While robust prevention programs have created downward trends in HIV infection in many of America’s largest cities, rates are increasing in rural areas. In 2010, the two U.S. counties with the highest prevalence of HIV were both rural counties (Walker County, Texas and Union County, Fla.). And, the proportion of Black, Hispanic and other minority populations exceeds the nation in seven of the eight highest prevalence rural counties.
In recent years, nearly 50% of all new HIV infections have occurred in the South with 40% of all new cases coming from Alabama, Florida, Georgia, Louisiana, Mississippi, North Carolina, South Carolina, Tennessee and Texas.
Disposti says a cure would help destigmatize HIV as well. People who are HIV positive often store drugs at the Resource Center, because they fear coming out to their families. A functional cure for HIV could change that for thousands.