Novel Methods to Eradicate HIV Reservoirs

In a summer update, we highlighted research from the amfAR Institute for HIV Cure Research at the University of California, San Francisco, involving a drug developed to fight cancer in a “shock and kill” approach to curing HIV. The authors concluded that findings from such a line of research underscore “the emerging ties between cancer and HIV treatment through shared drug targets.”

 Dr. Cheryl Cameron

Dr. Cheryl Cameron

Now in an article in the December 2017 issue of PLoS Pathogens, amfAR-funded scientists Drs. Cheryl Cameron from Case Western Reserve University in Cleveland and Franck Dupuy from McGill University in Montreal, with colleagues from both institutions, Emory University in Atlanta—including amfAR board member Dr. Raymond Schinazi—and the University of Montreal, explore using other drugs approved to treat other diseases to eradicate HIV.

The investigators studied two FDA-approved drugs, ruxolitinib, used to treat a bone marrow disorder known as myelofibrosis and some cases of lymphoma, and tofacitinib, used to treat rheumatoid arthritis and inflammatory bowel disease. These agents share a mechanism of action: inhibition of a normal cell protein known as Jak, a key promoter of inflammation.

 Dr. Franck Dupuy

Dr. Franck Dupuy

In test tube studies, the researchers used concentrations of the two drugs that are typically found in the blood of the patients taking them. They were able to block HIV production from infected T cells, inhibit activation of the virus from latently infected cells, and reduce the number of latently infected cells in HIV-infected individuals on antiretroviral therapy. This was accomplished without suppressing immune function.

The authors concluded: “Jak inhibitors represent a potential therapeutic modality that addresses a clinical need which traditional direct-acting antiviral agents that interfere with steps in the viral replication cycle have not been successful.”

Indeed, the role of ruxolitinib in reducing inflammation associated with HIV infection is currently being evaluated in a National Institutes of Health-funded clinical trial. Inflammation is believed to contribute to the persistent HIV reservoir, the primary barrier to a cure.

Dr. Laurence is amfAR’s senior scientific consultant.