Image Credit: Seth Pincus, Elizabeth Fischer and Austin Athman, National Institute of Allergy and Infectious Diseases/NIH
In September 2021, The US Food and Drug Administration (FDA) gave biotechnology company Excision BioTherapeutics approval to begin phase 1/2 of their human trials of CRISPR gene editing as a treatment for HIV.
The treatment, named EBT-101, uses CRISPR to cut out the HIV genome in three places to deactivate the virus cells. The one-time treatment is a “functional cure”, which means HIV can remain in the body, but cannot mutate or affect the patient. Excision’s CEO Daniel Dornbuch told news outlet FierceBiotech “If you just make a single cut, the virus can mutate around it. We make multiple cuts to deactivate the viral genome”.
CRISPR works by using the protein Cas9 and a guide piece of RNA, binding to a specific sequence of DNA and then ‘cutting’ at the target. When the cut repairs, there are mutations that disable the targeted gene.
According to UNAIDS, in 2020 there were 37.7 million people across the globe living with HIV, and in the same year 1.5 million more people were newly infected. More than 40 years after the first fatal cases of HIV/AIDS, we are still without a cure.
Incredible advances in research have already been made; there are now effective treatments on the market for HIV, meaning that those affected can manage the condition. However, in 2017, only 19.5 million people were receiving this treatment.
The current treatment regimen for HIV is antiretroviral therapy, commonly known as ART. ART is very effective as it combines multiple drugs to target HIV at multiple stages of its life cycle. A well-known drug used in the combination is Tenofovir, which works by inhibiting HIV-1 reverse transcriptase. If taken correctly, ART reduces the number of particles of HIV in the blood to an ‘undetectable’ viral load.
An undetectable viral load is defined in the UK as under 200 copies per millilitre of blood, and this is regularly monitored between periods of six to 12 months. This prevents the infected person from developing symptoms and means they are considered virally suppressed and unable to pass on HIV.
Though the benefits of taking this treatment greatly outweigh the risks - immunity levels remain healthy and HIV cannot be transmitted - it unfortunately involves taking multiple drugs everyday for the rest of your life, which undoubtedly can take an emotional and physical toll. This treatment plan is hard to follow, the drugs can have an array of side effects and if the treatment is not taken consistently, the virus starts copying itself in the body, viral load increases and the body develops drug resistance.
As well as the side-effects, dealing with the stigma that still surrounds HIV/AIDS can cause many to avoid taking these treatments altogether. Though this has greatly improved since the 90’s through educating the general public on the disease, this is not an ideal solution.
The next stages of the human trials for EBT-101 will include those on antiretroviral therapy. These patients will continue on treatment as normal for three months before being taken off to check if EBT-101 has been effective.
How likely is it that it will be effective? All previous non-human primate trials have shown that EBT-101 reached every tissue where HIV reservoirs were present, and successfully removed the pro-viral genome sites.
HIV/AIDS is a disease that feeds off inequality, with marginalised groups being most affected. The affected populations that face the most discrimination include the LGBTQ+ community, sex workers, and often in low economically developed countries such as in Sub-Sarahan Africa, adolescent girls and young women are particularly vulnerable. Therefore the breakthrough of EBT-101 could be immensely beneficial to the world as an alternative to the life-long daily treatment currently in place. As a one-time treatment will also be much less expensive, the inequality surrounding the diseases would also be reduced.