Veteran HIV researcher Robert Siliciano explores innovative paths toward an HIV cure at January seminar
Left to right: Kneeshe Parkinson, Javan Kisaka, Elvin Geng, Robert Siliciano, Liang Shan, George Kyei, Anthony Boatengat, Ishmael Aziati, and Prince Parbie at WashU after Silciano’s talk on January 21, 2025.
The Midwest D-CFAR and WashU Department of Molecular Microbiology co-hosted the HIV Translational Grand Rounds (HIG-R) and Microbiology Seminar Series on January 21, featuring Robert F. Siliciano, MD, PhD, professor of medicine at Johns Hopkins University. Dr. Siliciano has been researching HIV for over 35 years and is renowned for his work on HIV latency, a stage of infection when the virus is present but not replicating and therefore not causing symptoms. His work has revolutionized the scientific understanding of how the T cell reservoir is established and maintained, paving the way for innovative treatments and potential cures.
Scientists have been working on a cure for HIV for decades, but the unique biology of the virus and its intimate relationship with the host cell make it especially challenging to eliminate. Fortunately, people living with HIV can manage their infection and, in many cases, live long, healthy lives by taking antiretroviral therapies (ART). “There are 40 million people living with HIV,” Dr. Siliciano emphasized. “Almost all of them would die of AIDS without lifelong treatment with antiretroviral drugs.”
In his talk, Dr. Siliciano detailed how latent infection occurred in resting memory T cells whose slow decay guarantees lifetime persistence of the virus even when treated with ART. He noted that many scientists have tried to eliminate the viral reservoir by using latency-reversing agents to activate infected cells, subsequently making them susceptible to immune clearance, but this approach has shown limited success. Alternatively, enhancing immune responses to suppress the virus in the absence of ART holds promise for attaining a “functional” cure.
Highlighting recent findings by his group, Dr. Siliciano elaborated on how the reservoir size is maintained in people on long-term ART due to proliferation of latently infected memory T cells. This clonal proliferation was shown to be mainly driven by exposure to antigens. The good news is that the host antibody response is able to elicit autologous neutralizing antibodies (aNAbs) that effectively neutralize a significant majority of viruses persisting in the latent reservoir. However, a subset of reservoir viruses he termed aNAb-resistant reservoir viruses, escapes this immune response, driving virus rebound when treatment is interrupted. Dr. Siliciano suggested that inducing effective immune responses to block the outgrowth of the small subset of aNAb-resistant reservoir viruses could lead researchers to a cure.
During his visit, Dr. Siliciano took time to meet with students and early-stage investigators at WashU, encouraging them to pursue careers in the HIV field. He advised them to be open minded in their scientific thinking, and willing to adapt their understanding based on new evidence.
Dr. Siliciano reinforced the importance of interdisciplinary collaboration and open-minded inquiry in tackling the global challenge of HIV. His work underscores that while the path to a cure is complex, the scientific community is making steady progress toward solutions that could transform the lives of millions worldwide.
Written by Prince K. Parbie, PhD. Edited by April Houston.