CRISPR gene therapy appears safe, but claims of an imminent HIV cure are premature – Liz Highleyman, AIDSMap, November 3, 2023
Three people were gene-edited in an effort to cure their HIV. The result is unknown. – Antonio Regalado, MIT Technology Review, October 25, 2023
Excision BioTherapeutics Presents Positive Interim Clinical Data from Ongoing Phase 1/2 Trial of EBT-101 for the Treatment of HIV at ESGCT 30th Annual Congress – Excision BioTherapeutics Press Release, October 25, 2023
CRISPR/Cas9 is an assemblage of proteins derived from bacteria that may have the potential to target and disable (or eliminate) HIV’s genetic code in the reservoir of virus-infected cells that persist despite antiretroviral therapy (ART).
In recent years, laboratory studies of CRISPR/Cas9 as a potential curative approach in HIV have repeatedly generated misleading media headlines (see prior Media Monitor posts on the topic).
On Monday October 30, the British news outlet the Daily Mail continued this unwelcome trend with a headline falsely claiming that a cure for HIV “could be months away.”
The article is based on a conference presentation (and associated press release) that reported only preliminary safety results from three participants in the first human trial of a CRISPR/Cas9 approach in HIV. The presentation provided no information whatsoever about anti-HIV effects or efficacy.
The bottom line is that there was no evidence in the conference presentation to suggest that an HIV cure “could be months away.” The headline was likely written by an editor to attract engagement and clicks to benefit advertising revenue.
The first paragraph of the Daily Mail article also incorrectly states: “gene editing experts believe they are on the cusp of curing HIV.” No actual gene editing experts are quoted, and to TAG’s knowledge that’s because none believe “they are on the cusp of curing HIV.”
The article later quotes the scientist William Kennedy from Excision Biotherapeutics (the company conducting the clinical trial), who makes no claims about an HIV cure being imminent. Instead, the company is emphasizing that the apparent safety of the lowest dose given in the study means that they can progress to testing higher doses.
The excellent community-based British news website AIDSMap has since published a thorough and detailed article by Liz Highleyman explaining why the Daily Mail headline is wildly premature and off base.
There are several additional possible caveats regarding the CRISPR/Cas9 approach that underscore the uncertainty regarding potential efficacy in this first trial:
- The evidence that the intervention might reduce the size of the HIV reservoir and lower the risk of viral load rebound after stopping ART comes from humanized mice, which have many shortcomings as a model for human HIV infection.
- Researchers have presented very limited evidence that the approach can reduce the size of the SIV reservoir in macaques, which are considered a better model than humanized mice. An initial claim that a measure of the SIV reservoir known as the quantitative virus outgrowth assay (QVOA) showed negative results was made in a presentation at CROI 2019, but was not included in the published paper describing the study outcomes. Also mentioned at CROI 2019 were plans for an ART interruption study in macaques to assess whether SIV viral load rebound was reduced or prevented, but this study did not take place – Excision Biotherapeutics decided to move into humans instead.
- The clinical trial is currently only able to recruit people assigned male sex at birth due to an unspecified concern on the part of the U.S. Food and Drug Administration regarding reproductive toxicity (the aim is to expand enrollment to include people assigned female sex at birth as soon as possible).
- In the clinical trial, the CRISPR/Cas9 gene editor targeting HIV is delivered by an adeno-associated virus vector (AAV9) and it’s not clear how efficiently this delivery vehicle will enter CD4 T cells, where most of the HIV reservoir resides.
- It’s uncertain how well the approach can target the genetically diverse HIV variants present in a person living with HIV.
- The clinical trial is designed to allow participants to undergo an ART interruption if certain criteria are met after 12 weeks of follow up. The criteria are thought to be based on whether the participant experienced a reduction in the size of their HIV reservoir. The fact that the trial has been open for nearly two years but there has been no mention of any participant undergoing ATI might suggest that significant reductions in the size of the HIV reservoir have not been documented, at least yet. This would accord with the company’s emphasis on progressing to the testing of higher doses.
In conclusion, the potential efficacy of Excision Biotherapeutics CRISPR/Cas9 technology in people with HIV remains entirely unknown. Until additional information becomes available from the ongoing clinical trial, the prospects for the approach cannot be judged.