HIV infection is treatable, but not curable.

Antiretroviral therapy (ART) prevents HIV from replicating and passing it on to other people, but the virus stays in the body.

This is because HIV hides in the genome of long-lived immune cells during therapy, where it is protected from antiretroviral drugs and the immune system.

Those affected must therefore take the medication for life.

If the treatment is stopped, the latent viruses report back and quickly circulate in the blood again.

All attempts to drive them out of their reservoirs have so far failed.

Thomas Uldrick from the Fred Hutchinson Cancer Research Center in Seattle and his colleagues show in "Science Translational Medicine" that a cancer drug may be able to do this.

However, the indications are still vague.

The active substance is the therapeutic antibody pembrolizumab, which releases a brake on the immune system and brings immune cells out of their lethargy.

In cancer medicine, the unleashing of the immune system – so-called checkpoint inhibition – has triggered euphoria, although only a few tumor patients have benefited from it so far and the side effects are considerable.

Lure the viruses out of hiding

Why could the antibody be a glimmer of hope?

During antiretroviral therapy, HIV hides in depleted CD4-positive memory cells that have taken themselves out of the line of fire via the brake protein PD-1.

The HIV genes are hardly read there and translated into proteins, although the genome of the immune cells is still active.

As a result, the immune system has no indication of the latent viruses.

In order to unmask them, the virus genes would have to remain active and form HI viruses that are capable of replication.

Uldrick and his colleagues suspect that PD-1 could be the right lever for unmasking the latent HI viruses.

Not only does the protein dampen down memory cells, but it could also make HIV feel safe in those cells.

That's why they want to block PD-1 with pembrolizumab and thus activate the immune cells.

Because HIV-infected people without cancer could not reasonably be expected to receive treatment with antiretroviral drugs and pembrolizumab, Uldrick and his colleagues studied 32 patients who had both diseases and were therefore receiving both therapies.

After the first infusion, the amount of viral RNA in the immune cells and blood increased.

The antibody must have activated the virus.

The researchers also observed that the amount of immune cells with viable virus increased 1.4-fold after six treatment cycles.

However, these effects were not enough to expel HIV from the places of refuge.

Uldrick and his colleagues now hope that success will be greater in people who only have HIV and don't have cancer.

open questions

Many more questions are still open.

How often and at what intervals would the treatment have to be repeated?

Is there a dose at which the side effects are so low that treating infected people who are doing very well with antiretroviral therapy is justified?

In addition, previous studies with another antibody against PD-1, nivolumab, have not shown any activity against latent HI viruses.

Researchers from the University of Oxford also report in "Science" on a more virulent HIV-1 variant of subtype B. This apparently emerged more than twenty years ago, but has only now been discovered in 109 HIV-infected people in the Netherlands.

The variant produces a higher viral load in the blood, is more contagious and leads to the death of CD4-positive T cells more quickly and thus to the immune deficiency AIDS.

Nevertheless, the new variant is not "Super Aids," writes Joel Wertheim from the University of California in San Diego in an accompanying comment.

Antiretroviral therapy and the usual protective measures continue to work.