Dormant virus in people with HIV wakes up with medicine against parasites

HIV hides in immune cells and remains there in a dormant state

A commonly used anti-parasitic drug awakens the virus from a dormant state in people with HIV. Scientists at Erasmus MC discovered this in the first study in which this drug was tested in people living with HIV. “The road to recovery is still long.”

In the quest to cure HIV, scientists must address an annoying property of the virus. HIV hides in immune cells and remains there in a dormant state. HIV medication keeps the virus under control, but as soon as someone stops taking the medication, the virus rears its ugly head again.

To get the virus completely out of the body, it must first be awakened. Then the immune system can recognize and clear the cells in which HIV hides.

Pyrimethamine
Researchers at Erasmus MC have now shown that a drug against parasites may play a role in this. It concerns the drug pyrimethamine, which is used, for example, in the infectious disease toxoplasmosis. Treatment with pyrimethamine awakens the virus from its dormant state, discovered internist-infectiologist Henrieke Prins and molecular virologists Raquel Crespo and Cynthia Lungu.

The study, published in Science Advances, involved 28 people living with HIV. The scientists divided the participants into four groups: one group received pyrimethamine, one group received another drug that the researchers expected would awaken the virus, one group received both drugs, and the last group received nothing. The treatment lasted two weeks and was in addition to standard HIV medication.

Make reservoir smaller
In people from the group who received pyrimethamine, the researchers saw indications that the virus was awakening from its dormant state. The second drug called valproic acid did not and did not enhance the effect of pyrimethamine. The latter was unexpected. ‘We had expected, after experiments in the laboratory, that the two substances would reinforce each other,’ says Prins.

Pyrimethamine thus awakens the virus, but it does not cause the number of body cells with dormant virus to decrease. Scientists call this the HIV reservoir. ‘Our hypothesis was that the immune system would detect and clear the awakened virus. That appears not to be happening. The HIV reservoir remains the same,’ says Lungu. ‘Another intervention may be needed to actually make the reservoir smaller,’ adds Crespo.

White men
Follow-up studies should show what pyrimethamine should be combined with to permanently remove the virus from the body. ‘We also have to find out whether pyrimethamine works in the same way in all people with HIV, since this study mainly involved white men,’ says Lungu.

The researchers are pleased with their results, but are wary of being too optimistic. ‘We are proud that our study shows that a cheap, widely used and safe drug has promising results in awakening the virus. But the road to a cure for HIV is still long. It is very difficult to say how long that will take,’ says Crespo.

‘We are proud that a cheap, widely used and safe drug gives promising results’

The project is a textbook example of what is called bench to bedside research. It started with the discovery in the lab of a protein complex involved in keeping HIV asleep. Subsequently, pyrimethamine emerged from a screening as a substance that can inhibit this protein complex. This eventually led to the setting up of this first clinical study of the combination of drugs in people with HIV.

Several areas of expertise also came together in the study itself. Prins: ‘For example, the Erasmus MC hospital pharmacy: they set up their own assay to measure the pyrimethamine concentration in the blood. We are now the only ones in the Netherlands who can do this.’

EHEG: together against HIV
The researchers are part of the Erasmus MC HIV Eradication Group (EHEG). Scientists from different departments and disciplines work together in this against HIV.

Bron: Erasmus MC / Berit Sinterniklaas

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