Emory University's pioneering work with a class of small molecules known as JAK (janus kinase) inhibitors continues to show how HIV might be cured after a second patient who received the treatment was declared to be in long-term remission.
The use of JAK inhibitors against HIV began with a ground-breaking discovery led by Christina Gavegnano, an assistant professor with appointments in the Emory School of Medicine and the Emory College of Arts and Sciences Center for the Study of Human Health.
The announcement, involving an individual known as the "Oslo patient," was shared at a conference earlier this month. Doctors said the patient received ruxolitinib, a first-generation JAK inhibitor, for complications following a stem cell transplant from a sibling to treat cancer.
Ruxolitinib works as an immunomodulatory drug that may also reduce viral reservoirs. Its potential against the HIV reservoir was first documented by Gavegnano in 2012 and later established in a subset of participants in the AIDS Clinical Trial Group Sponsored Phase 2a study led by Emory infectious disease professor Vincent Marconi, with Gavegnano as a key co-investigator. The first case of ruxolitinib as part of a potentially curative regimen was documented in the "Geneva patient," who was declared to be in remission from HIV in 2023 following treatment that included the drug.
The drug's potency against the HIV reservoir in the Oslo and Geneva cases points to a new path toward a cure. Researchers previously declared individuals living with HIV cured following stem cells transplants — an expensive and risky procedure that limits its use — from donors with a mutation that makes them resistant to the virus. While the Oslo patient's stem cell donor had the mutation, the Geneva patient received cells from someone who did not have the mutation.
Gavegnano first came up with the idea to use JAK inhibitors against HIV while working on her pharmacology PhD studies at Emory. Her approach was to reconfigure JAK inhibitors, which were already FDA-approved for inflammatory conditions such as rheumatoid arthritis, to control inflammation from HIV by blocking key pathways that allow the virus to persist. This discovery became Gavegnano's PhD thesis.
Now she's preparing to co-lead a new clinical trial using baricitinib, a second-generation JAK inhibitor, to further test the potential for sustained HIV remission without requiring lifelong antiretroviral therapy or a stem cell transplant.
"A life's work of elucidating how JAK inhibitors may provide a key to a previously locked door of curing HIV," Gavegnano says. "The courageous efforts from the Geneva patient and his team, and now the Oslo patient and his team, are paving the way for future collaborations and potential for a globally accessible cure for HIV."
Emory will continue to be on the forefront of the research. The first-ever clinical trial using baricitinib for HIV cure research will be co-led by Gavegnano; Marconi, professor of medicine and global health in the School of Medicine; and Andrew H. Miller, professor and vice chair for research in the Department of Psychiatry and Behavioral Sciences in the School of Medicine.
Their study will examine whether extending JAK inhibitor therapy beyond six months can further deplete HIV reservoirs and lead to long-term remission, in the absence of traditional antiretrovirals. This represents a potential turning point in HIV cure research, Gavegnano says.
