Reduced HIV reservoir through combination of antiretroviral therapy and the anticancer drug dasatinib

Eliminating the HIV reservoir, that is, the cells of the immune system in which the virus hides, is one of the greatest challenges facing medicine today. The persistence of the reservoir prevents people with HIV, despite receiving antiretroviral treatment, from completely eliminating the virus from their bodies and, therefore, from being cured. Now, a study published in Biochemical Pharmacology in which the Retrovirology and Clinical Studies Group (GREC) of IrsiCaixa has participated, shows that the anticancer drug dasatinib, in combination with antiretroviral treatment, reduces the reactivation ability and the size of the viral reservoir in people with chronic myeloid leukemia. Compared to people with HIV receiving antiretroviral treatment and with an undetectable viral load, the three individuals who participated in the study had a reservoir five times smaller and with a reactivation ability four times smaller.

Dasatinib, an anticancer drug capable of reducing the HIV reservoir

People with HIV who subsequently develop chronic myeloid leukemia have a very small viral reservoir. With this observation, IrsiCaixa researchers, together with professionals from different national and international scientific institutions, initiated a laboratory study in which they determined that dasatinib, an anticancer drug used in the treatment of this type of leukemia, could have an important antiviral role against HIV. Specifically, they found that this drug is capable of blocking the reactivation and proliferation of the viral reservoir, as well as preserving the antiviral activity of the SAMHD1 molecule, which is responsible for blocking HIV replication in cells.

Now, the same scientific team has analyzed the effect of dasatinib on the size, composition and reactivation ability of the viral reservoir in three people with HIV and chronic myeloid leukemia receiving both antiretroviral therapy and dasatinib. The team has been able to demonstrate that these individuals have a viral reservoir that is five times smaller and four times less likely to reactivate compared to people with HIV on antiretroviral therapy alone. "Moreover, thanks to studies we have done in the laboratory, we have been able to observe that, to achieve these results, only one ninth of the concentration of dasatinib recommended in the treatment of chronic myeloid leukemia would be necessary", explains Javier Martínez-Picado, ICREA researcher at the GREC group at IrsiCaixa. "By administering a lower dose of the anticancer drug, we would be reducing the risk of possible side effects", he adds.

These results, therefore, reinforce the idea that antiretroviral treatment combined with dasatinib could contribute to the reduction of the viral reservoir in people with HIV.

A very stable viral reservoir

There is currently no cure for HIV. People living with the virus and receiving antiretroviral treatment, despite managing to reduce the viral load to the point of being undetectable –and therefore untransmissible– maintain a viral reservoir, that is, a group of cells in which the virus is inactive and remains hidden. "Thanks to the scientific literature, we know that the cells that form the HIV reservoirs are characterized by being very stable and have a half-life of almost 4 years", explains Mari Carmen Puertas, senior laboratory technician in the GREC group at IrsiCaixa.

"The study presented demonstrates that we can reduce this reservoir in people with HIV and chronic myeloid leukemia. This is a big step, but this context is very limited. We keep on doing studies in mice to see the effect of this drug in different antiretroviral therapy contexts so that it can then be applied in humans", says Maria Salgado, associate researcher at the GREC group at IrsiCaixa.

In this sense, it is essential to continue research along this path to find strategies capable of eliminating or reducing the size of this reservoir. "Our ultimate goal is to make the size of the reservoir so small that the immune system itself can keep it under control, as this step could be essential to achieve a functional cure for HIV", concludes Mayte Coiras, researcher at the Instituto de Salud Carlos III and lead author of the study.