Eradicating HIV—amfAR-Funded Researchers Shed New Light on HIV Persistence
By Jeffrey Laurence, M.D., and Rowena Johnston, Ph.D.
Dr. Nicolas Chomont
July 10, 2009—Despite our best efforts, development of an effective AIDS vaccine appears stymied, with no success in any clinical trial. In contrast, steady progress is being made towards eradicating HIV—in other words, curing AIDS. amfAR fellow Dr. Nicolas Chomont, together with amfAR grantees Drs. Elias Haddad, Jean-Pierre Routy, and Rafick-Pierre Sékaly, writing in the online edition of the prestigious journal Nature Medicine, have developed a model by which we might approach the goal of an AIDS cure.
The major impediment to eradicating HIV is its ability to lie dormant in a reservoir. Patients successfully treated with highly active antiretroviral therapy (HAART) have no detectable virus in their blood, but they do have a small number of cells—approximately a million—that are infected with latent virus. HIV thereby persists beyond the reach of both the immune system and standard anti-HIV drugs. These cells will remain infected for the life of the patient, poised to resume virus production should treatment stop or fail.
Chomont, Routy, Haddad, Sékaly and colleagues, working at the University of Montreal and McGill University, first noted that HIV persists in two types of memory T cells: the “central memory” or TCM cell, and the “transitional memory” or TTM cell. Memory T cells can persist for decades, and if they are infected with HIV, they represent a significant portion of the viral reservoir. Early anti-HIV treatment—within the first year of infection—can limit the number of such cells infected, but it would still take a person’s lifetime to eradicate such reservoirs with HAART alone. But Chomont and associates uncovered different driving forces for infection for each type of memory T cell—foreign antigens for TCM and immune hormones such as IL-7 for TTM.
Based on their test-tube experiments, they concluded, “New therapies should [include] inhibitors of IL-7 or pathways associated with ‘stem cell-ness,’ such as those developed for the treatment of leukemias and cancers. [In this manner] eradication of virus could become a more realistic endeavour.”
Dr. Laurence is amfAR’s senior scientific consultant and Dr. Johnston is vice president and director of research.