Formula predicts ideal stem cell dose to cure HIV

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  • Scientist have found that under favourable conditions, stem cell transplants could cure HIV
  • The model uses gene editing to remove the molecules that HIV is attracted to and then returns the stem cells to the patient 
  • Through this model, scientists hope that HIV patients will no longer have to take ARVs 

Scientists have found the optimal conditions for stem cell transplant that could control the HIV virus without the need for a daily pill, according to a new study.

The study published in eLife showed that finding the right balance of stem cell dose, cell type and timing of antiretroviral therapy (ART) could potentially lead to eliminating HIV in patients.

Learning from previous stem cell transplants

Previously, the world has seen two patients who were cured of HIV through stem cell transplants from donors that lack a molecule called CCR5, which HIV is attracted to. They are popularly known as the London and Berlin patients.

The team of scientists investigated the use of autologous stem cell transplants. Autologous cell  transplantation is when stem cells are removed from a person, stored, and later given back to that same person. The bone marrow stem cells are removed from the patient, engineered using gene editing, so that they lack CCR5, and then returned to patients. 

"The major obstacle to HIV eradication is a latent reservoir of long-lived infected cells, and cure strategies aim to eliminate all infected cells or permanently prevent viral reactivation from latency. We wanted to recreate the cures seen in the Berlin and London patients but with reduced toxicity," explains first author Fabian Cardozo-Ojeda in a press release.

Determining the model

Researchers developed a multi-stage mathematical model to study the dynamics of residual and transplanted stem cells, HIV viral load, and how these are affected by the timing of ART withdrawal. 

They based their model on data from 22 monkeys with the monkey version of HIV. These animals were treated with a stem cell transplant, with or without CCR5 gene editing. A large portion of the animals then had their ART stopped after a year.

The immune cell dynamics and viral load differed between the animals, but there was a consistent theme that the viral load after ART withdrawal was higher in transplanted animals than untreated ones. This suggests that stem cell transplantation might reduce existing immune cell immunity to HIV.

They used their model to calculate the conditions required to achieve viral control after ART withdrawal. They found two important conditions: the first was ensuring a dose of at least five times as many transplanted stem cells as there are residual stem cells after the transplant, and the second was allowing the CCR5-edited stem cells to be at least 76–94% of the total transplanted stem cell population.

"Our model predicts that viral control might be possible following autologous, gene-edited stem cell transplants if a sufficient proportion of edited stem cells are allowed to repopulate the blood before ART is stopped. The results illustrate the capabilities of mathematical models in optimising strategies for HIV cure,” says senior author Prof Joshua Schiffer.

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