Researchers look to already-approved therapies to target dormant HIV
Research question
How do researchers identify agents that might be useful to an HIV cure? One approach is to screen drugs that have been FDA-approved and are in common use for diseases not related to HIV. Part of the process involves using test-tube assays that mimic mechanisms critical to HIV latency.
A team of researchers in Australia working with colleagues in Denmark were intrigued by early studies of an immune modulatory drug called pomalidomide. The drug is known to be effective against certain cancers—lymphomas, multiple myeloma, and Kaposi sarcoma—in people with and without HIV. High concentrations of the drug—levels much greater than would be achievable or safe in humans—could reverse the HIV latent state and induce death of infected cells in the test tube. This was of interest because pomalidomide accelerates the destruction of two “pro-survival proteins,” Ikaros and Aiolos, involved in keeping HIV latent cells alive.
But would clinically useful doses of pomalidomide have similar effects in vitro when tested against cells from people living with HIV on long-term antiretroviral therapy?
Findings
Clinically appropriate concentrations of pomalidomide did indeed affect levels of proteins linked to the survival of latently infected T cells but did not translate to enhanced clearance of these cells. In terms of a “shock and kill” strategy to wake up dormant HIV and then eradicate infected cells via immune mechanisms, pomalidomide also showed no effect in test-tube studies.
Impact
The authors conclude that pomalidomide showed “no evidence of latency reversal or selective death of infected cells.” This is an important piece of negative data to inform future HIV cure research.
amfAR’s role
amfAR was a funder of this research. amfAR grantee Prof. Sharon Lewin, Director of the Peter Doherty Institute for Infection and Immunity, University of Melbourne, was a co-author of the paper.
Original article
http://www.ncbi.nlm.nih.gov/pubmed/39902962
Dr. Laurence is amfAR’s senior scientific consultant.
