Originally published 2019-07-30.
© Karin Schermbrucker/UNICEF
No, HIV has not been cured in people by CRISPR. What happened in July 2019 was a promising animal experiment: researchers in the United States combined a slow-release HIV medicine with CRISPR gene editing and found no trace of the virus afterwards in 9 of 23 specially prepared mice. The first human trial built on that idea started in 2022. It proved safe, but it did not stop the virus coming back once people paused their usual treatment.
Below is what the mouse study actually did, why it caused so much excitement, what the human trial showed, and where the search for an HIV cure stands for the roughly 40 million people living with the virus.
Why HIV is so hard to cure
HIV, the human immunodeficiency virus, attacks CD4 T cells, the white blood cells that coordinate the body's defences against infections. Left untreated, the infection slowly wears the immune system down until it reaches AIDS, the stage at which ordinary germs and some cancers become life-threatening. Since the epidemic was recognised in the early 1980s, AIDS-related illnesses have killed tens of millions of people.
Modern antiretroviral therapy (ART) changed that picture completely. Daily medicines stop the virus from copying itself, and most people who take them consistently can expect a near-normal lifespan. When the amount of virus in the blood falls to an undetectable level, the US Centers for Disease Control and Prevention confirms that a person will not pass HIV on through sex, a message known as Undetectable = Untransmittable, or U=U.
The catch is that ART controls HIV; it does not remove it. Shortly after infection, the virus writes its own genetic code into the DNA of some of the cells it infects. Many of those cells go quiet and form what scientists call the latent reservoir, hidden in places such as lymph nodes, the spleen, bone marrow, the gut and the brain. Medicines cannot reach a virus that is not actively replicating, so if treatment stops, these sleeping copies wake up and the infection returns, usually within weeks.
Any true cure therefore has to do one of two things: clear out every infected cell, or permanently stop the hidden virus from ever restarting.
What the 2019 mouse study did
The paper, published in Nature Communications on 2 July 2019, came from two teams that had been working separately. Howard Gendelman at the University of Nebraska Medical Center had developed LASER ART, a long-acting, slow-release form of standard HIV drugs. Kamel Khalili at the Lewis Katz School of Medicine at Temple University had spent years designing CRISPR tools aimed at the HIV genome. The first author was Prasanta Dash.
Ordinary mice cannot catch HIV, so the researchers used "humanised" mice whose immune systems had been rebuilt from human blood-forming stem cells taken from umbilical cord blood. These animals carry human T cells that the virus can infect.
The treatment came in two steps:
- Suppress first. Infected mice received injections of LASER ART, a nanoformulated mix of dolutegravir, rilpivirine, lamivudine and abacavir. The drugs are released slowly and build up in tissues where HIV likes to hide, pushing the virus down to very low levels for weeks.
- Then cut. Once the drug levels had faded, each mouse received a single dose of CRISPR-Cas9 carried by a harmless virus (AAV9). The editing tool was guided to two regions of the HIV genome, the LTR and Gag sequences, so that it could snip out large pieces of the virus's DNA from the infected cells.
The team then waited to see whether the virus rebounded, and examined tissues with highly sensitive tests for any remaining viral DNA or RNA. As a final check, they transferred immune cells from apparently cured mice into fresh animals to see whether any hidden virus would start growing again.
The result, and its limits
Every mouse that received only LASER ART, or only CRISPR, saw the virus come back. In the groups that received both, there was no detectable HIV in 9 of 23 animals across three experiments, about 39 percent. The authors described it as "a third or more" of the dual-treated mice.
That was a genuine first: a sequential treatment that seemed to remove HIV completely from living animals rather than just keep it down. It is also easy to overstate, so a few points matter:
- It worked in fewer than half of the mice, and the researchers wrote that why some animals cleared the infection and others did not was "incompletely understood."
- The group sizes were small, and follow-up lasted weeks to a few months, partly because the humanised mice develop graft-versus-host disease.
- "Undetectable" always depends on the sensitivity of the test. In one group a mouse with no virus in its blood still had viral DNA in its tissues.
- Mice are not people. The human reservoir is larger, older and spread across a much bigger body.
Khalili and Gendelman said clearly at the time that this was a proof of concept, not a cure for humans. Some independent experts, such as City of Hope gene-therapy researcher Kevin Morris, welcomed the result but raised concerns about the side effects of gene editing in people. Reports in 2019 suggested human trials could begin as early as summer 2020. In the end they took longer.
What happened when the idea reached people
Khalili's CRISPR approach was developed into a therapy called EBT-101 by the company Excision BioTherapeutics. Its phase 1/2 trial (NCT05144386) started in 2022. Volunteers were already on ART with undetectable virus; each received a single infusion of the gene-editing therapy.
Results presented by Rachel Presti at the American Society of Gene & Cell Therapy meeting in May 2024, and reported by aidsmap, showed the treatment was safe and well tolerated in five participants. That matters, because safety was the first question any gene therapy has to answer.
The cure question was different. Three participants stopped their usual HIV medicines to test whether the virus stayed away, and in all three it came back, so they restarted ART. In one person it stayed suppressed for 16 weeks, longer than usual. The most likely explanation is that the therapy did not reach every cell carrying latent HIV, and even a small number of untouched cells is enough to restart the infection. The company said it was testing a higher dose and exploring other delivery methods, such as lipid nanoparticles.
In other words, the mouse result has not yet translated into a human cure, which is the normal path for most early laboratory breakthroughs.
Have any people been cured of HIV?
A small number have, but not with CRISPR. Timothy Ray Brown, known as the "Berlin patient," became the first person considered cured. In 2007 he needed a stem-cell transplant for leukaemia, and his doctors chose a donor with two copies of the CCR5-delta32 mutation, which removes the doorway most HIV strains use to enter cells. He stayed free of detectable HIV without medication until his death from cancer in 2020. More than a decade later, Adam Castillejo, the "London patient," was reported cured after a similar transplant for Hodgkin lymphoma, and several further cases have been reported since.
These cases prove a cure is biologically possible, but they are not a treatment option for most people. A bone-marrow transplant is a dangerous procedure reserved for life-threatening blood cancers, matching donors with the mutation is rare, and Brown himself went through severe complications. Researchers study these patients to learn what a cure would require, and gene-editing approaches such as EBT-101 are, in part, an attempt to achieve similar protection without a transplant.
Other lines of research continue alongside gene editing, including vaccines, broadly neutralising antibodies and "shock and kill" strategies that try to wake the latent virus so it can be destroyed. An experimental vaccine reported in 2018 produced immune responses in people and rhesus monkeys, but no vaccine has yet been shown to prevent or cure HIV.
What this means for people living with HIV today
The honest takeaway is hopeful but patient. According to UNAIDS, about 39.9 million people were living with HIV in 2023, and about 30.7 million were on treatment. For them, the most important tool is still the one that already works: taking effective treatment consistently and keeping the virus undetectable, which protects their own health and their partners.
A few common myths are worth clearing up:
- "Scientists have cured HIV with CRISPR." Not in humans. The 2019 success was in a subset of mice, and the first human trial did not prevent rebound.
- "A cure means I can stop my medicines." Never stop or change HIV treatment on the basis of news reports. Experimental treatment interruptions happen only inside supervised trials. Talk to your doctor about any questions.
- "Undetectable means cured." No. Undetectable means the virus is controlled so well that it cannot be passed on through sex, but the hidden reservoir is still there.
The 2019 study still deserves its place in the story. It showed that suppressing the virus first and then cutting it out of infected cells could, at least in animals, remove HIV altogether, and it moved CRISPR from a laboratory idea into human trials within three years. The next step is reaching every last infected cell, safely, in a human body.
Sources: Dash et al., Nature Communications (2019): Sequential LASER ART and CRISPR treatments eliminate HIV-1 in a subset of infected humanized mice; aidsmap (May 2024): CRISPR gene therapy EBT-101 does not prevent HIV viral rebound; Wikipedia: Timothy Ray Brown; CDC: HIV treatment; UNAIDS fact sheet. Photo: Karin Schermbrucker/UNICEF.
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