Repurposed blood cancer drug may help suppress HIV
A study has found that a drug used to treat blood cancer can destroy dormant HIV in the body.The authors of a new study have changed the purpose of an existing blood cancer drug, using it to kill dormant HIV-infected cells that can reactivate the infection when suppressive antiretroviral therapy is interrupted. The drug could change the lives of people with HIV by eliminating the need for lifelong medication.
Blood cancers such as leukemia or lymphoma produce high levels of apoptotic B-cell lymphoma-2 (Bcl-2), a protein that helps cancer cells survive. The drug venetoclax, is a targeted therapy, a BH3 mimetic that specifically blocks Bcl-2, leading to programmed cancer cell death. Now scientists have used the drug for the first time to test its effectiveness against persistent HIV infection.
An experiment in mice showed that not all infected cells were sensitive to Bcl-2 inhibition during the six-week treatment course. Therefore, the researchers combined venetoclax with another BH3 mimetic, the Mcl-1 inhibitor S63845. Mcl-1 is another survival-promoting protein and a critical regulator of T-cell development and survival.
They found that treatment with S63845 alone for three weeks did not significantly delay viral recovery. However, using combined treatment with venetoclax and S63845 for three weeks, the researchers found that in 50% of the mice, the virus relapsed two weeks after stopping ART, while the remaining 50% had a recovery time of four weeks. The S63845 treatment is now in Phase I clinical trials as a blood cancer drug and is not yet on the market.
The study is published in the journal Cell Reports Medicine.