The formula predicts the ideal dose of stem cells to cure HIV


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Scientists have determined the optimal conditions after a stem cell transplant that could control HIV without the need for a daily pill, according to a study published today in eLife.

Finding the right balance between stem cell dose, cell type and timing of antiretroviral therapy (ART) can potentially lead to a spontaneous to cure of HIV.

There are only two cases of HIV cure so far: the Berlin Patient and the London Patient, both of which have undergone stem cell transplants with stem cell transplantation. cells of donors who lack the molecule CCR5, which HIV is attracted to.

“The main obstacle to HIV eradication is a latent reservoir of long-lived infected cells, and healing strategies aim to infected cells or permanently prevent viral reactivation through latency, ”explains lead author E. Fabian Cardozo-Ojeda, Senior Staff Scientist at the Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, USA, but with reduced toxicity. “

The team investigated the use of autologous stem cell transplants, in which bone marrow stem cells are removed from the patient, manipulated through gene editing so that they do not have CCR5, and then returned to patients. This technique is being tested in an early clinical trial in people with HIV, but the minimum number of CCR5-processed stem cells required for long-term remission or cure in the patients in Berlin and London was unknown.

To determine this, the researchers developed a multi-stage mathematical model to study the dynamics of leftover and transplanted stem cells, HIV viral load (the amount of virus in the blood) and how these are affected by the timing of stopping the ART. They based their model on data from 22 monkeys with monkey HIV who were treated with one stem cell transplant, with or without CCR5 gene editing. ART was discontinued after one year in a subgroup of the animals.

Immune cell dynamics and viral load differed between animals, but a consistent theme was that viral load after ART withdrawal was higher in transplanted animals than untreated. This suggests that stem cell transplantation could reduce existing immune cells’ immunity to HIV. The team speculated that this immunity could be restored if CCR5 is disrupted enough in the transplanted stem cells.

To investigate this, they used their model to calculate the conditions necessary to achieve viral control after ART withdrawal. They found two important conditions: The first was to ensure a dose of at least five times as many transplanted stem cells as there are residual stem cells after treatment. transplant, and the second was that the CCR5-processed stem cells make up at least 76-94% of the total transplanted stem cell population.

“Our model predicts that viral control is possible after autologous, gene-edited stem cell transplants if enough edited stem cells may repopulate the blood before ART is stopped, “concludes senior author Joshua T. Schiffer, associate professor at the Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center.” The results illustrate the capabilities of mathematical models in optimizing HIV cure strategies. . ”

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More information:
E Fabian Cardozo-Ojeda et al, Thresholds for post-rebound SHIV control after CCR5 gene-edited autologous hematopoietic cell transplant, eLife (2021). DOI: 10.7554 / eLife.57646
Journal information:

Quote: Formula predicts ideal stem cell dose to cure HIV (2021, January 12) Retrieved April 30, 2021 from

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